Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia.

PubMed

Pfau, Doreen B; Krumova, Elena K; Treede, Rolf-Detlef; Baron, Ralf; Toelle, Thomas; Birklein, Frank; Eich, Wolfgang; Geber, Christian; Gerhardt, Andreas; Weiss, Thomas; Magerl, Walter; Maier, Christoph

2014-05-01

Age- and gender-matched reference values are essential for the clinical use of quantitative sensory testing (QST). To extend the standard test sites for QST-according to the German Research Network on Neuropathic Pain-to the trunk, we collected QST profiles on the back in 162 healthy subjects. Sensory profiles for standard test sites were within normal interlaboratory differences. QST revealed lower sensitivity on the upper back than the hand, and higher sensitivity on the lower back than the foot, but no systematic differences between these trunk sites. Age effects were significant for most parameters. Females exhibited lower pressure pain thresholds (PPT) than males, which was the only significant gender difference. Values outside the 95% confidence interval of healthy subjects (considered abnormal) required temperature changes of >3.3-8.2 °C for thermal detection. For cold pain thresholds, confidence intervals extended mostly beyond safety cutoffs, hence only relative reference data (left-right differences, hand-trunk differences) were sufficiently sensitive. For mechanical detection and pain thresholds, left-right differences were 1.5-2.3 times more sensitive than absolute reference data. The most sensitive parameter was PPT, where already side-to-side differences >35% were abnormal. Compared to trunk reference data, patients with postherpetic neuralgia exhibited thermal and tactile deficits and dynamic mechanical allodynia, mostly without reduced mechanical pain thresholds. This pattern deviates from other types of neuropathic pain. QST reference data for the trunk will also be useful for patients with postthoracotomy pain or chronic back pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Somatosensory profiles in subgroups of patients with myogenic temporomandibular disorders and Fibromyalgia Syndrome.

PubMed

Pfau, Doreen B; Rolke, Roman; Nickel, Ralf; Treede, Rolf-Detlef; Daublaender, Monika

2009-12-15

Some patients with myofascial pain from temporomandibular disorders (TMD) report pain in extra-trigeminal body regions. Our aim was to distinguish TMD as regional musculoskeletal pain syndrome (n=23) from a widespread pain syndrome (FMS; n=18) based on patients' tender point scores, pain drawings and quantitative sensory testing (QST) profiles. Referenced to 18 age- and gender-matched healthy subjects significant group differences for cold, pressure and pinprick pain thresholds, suprathreshold pinprick sensitivity and mechanical detection thresholds were found. Pain sensitivity in TMD patients ranged between those of FMS patients and healthy controls. The group of TMD patients was inhomogeneous with respect to their tender point count with an insensitive group (n=12) resembling healthy controls and a sensitive TMD group (n=9) resembling FMS patients. Nevertheless sensitive TMD patients did not fulfil diagnostic criteria for FMS in regard to widespread pain as shown by their pain drawings. TMD subgroups did not differ with respect to psychological parameters. The sensitive subgroup was more sensitive compared to healthy controls and to insensitive TMD patients in regard to their QST profile over all test areas as well as to their tenderness over orofacial muscles and trigeminal foramina. However, sensitive TMD patients had a short pain duration arguing against a transition from TMD to FMS over time. Data rather suggest an overlap in pathophysiology with FMS, e.g. a disturbance of central pain processing, in this subgroup of TMD patients. Those patients could be identified on the basis of their tender point count as an easy practicable screening tool.

Lubiprostone does not influence visceral pain thresholds in patients with irritable bowel syndrome.

PubMed

Whitehead, W E; Palsson, O S; Gangarosa, L; Turner, M; Tucker, J

2011-10-01

In clinical trials, lubiprostone reduced the severity of abdominal pain. The primary aim was to determine whether lubiprostone raises the threshold for abdominal pain induced by intraluminal balloon distention. A secondary aim was to determine whether changes in pain sensitivity influence clinical pain independently of changes in transit time. Sixty-two patients with irritable bowel syndrome with constipation (IBS-C) participated in an 8-week cross-over study. All subjects completed a 14-day baseline ending with a barostat test of pain and urge sensory thresholds. Half, randomly selected, then received 48 μg day(-1) of lubiprostone for 14 days ending with a pain sensitivity test and a Sitzmark test of transit time. This was followed by a 14-day washout and then a crossover to 14 days of placebo with tests of pain sensitivity and transit time. The other half of the subjects received placebo before lubiprostone. All kept symptom diaries. Stools were significantly softer when taking lubiprostone compared to placebo (Bristol Stool scores 4.20 vs 3.44, P < 0.001). However, thresholds for pain (17.36 vs 17.83 mmHg, lubiprostone vs placebo) and urgency to defecate (14.14 vs 14.53 mmHg) were not affected by lubiprostone. Transit time was not significantly different between lubiprostone and placebo (51.27 vs 51.81 h), and neither pain sensitivity nor transit time was a significant predictor of clinical pain. Lubiprostone has no effect on visceral sensory thresholds. The reductions in clinical pain that occur while taking lubiprostone appear to be secondary to changes in stool consistency. © 2011 Blackwell Publishing Ltd.

Conditioned Pain Modulation in Women with Irritable Bowel Syndrome

PubMed Central

Jarrett, Monica E.; Shulman, Robert J.; Cain, Kevin C.; Deechakawan, Wimon; Smith, Lynne T.; Richebé, Philippe; Eugenio, Margaret; Heitkemper, Margaret M.

2013-01-01

Evidence suggests that patients with irritable bowel syndrome (IBS) are more vigilant to pain-associated stimuli. The aims of this study were to compare women with IBS (n = 20) to healthy control (HC, n = 20) women on pain sensitivity, conditioned pain modulation (CPM) efficiency and salivary cortisol levels before and after the CPM test; and examine the relationship of CPM efficiency with gastrointestinal, somatic pain, and psychological distress symptoms in each group. Women, ages 20–42, gave consent, completed questionnaires and kept a symptom diary for 2 weeks. CPM efficiency was tested with a heat test stimulus and cold water condition stimulus in a laboratory between 8 and 10 a.m. on a follicular phase day. Salivary cortisol samples were collected just before and after the experimental testing. Compared to the HC group, women with IBS reported more days with gastrointestinal and somatic pain/discomfort, psychological distress, fatigue, and feeling stressed. During the CPM baseline testing women with IBS reported greater pain sensitivity compared to the HC group. In the IBS group, CPM efficiency was associated with the pain impact (PROMIS) measure, daily abdominal pain/discomfort, psychological distress, in particular anxiety. There was no group difference in salivary cortisol levels. Overall, women with IBS exhibit an increased sensitivity to thermal stimuli. Impaired CPM was present in a subset of women with IBS. PMID:24463504

Effects of neonatal pain, stress and their interrelation on pain sensitivity in later life in male rats.

PubMed

Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Aloisi, Anna Maria

2016-08-31

Neonatal pain and stress induce long-term changes in pain sensitivity. Therefore their interrelation is a topical subject of clinical and basic research. The present study investigated the effects of inflammatory peripheral pain and stress of maternal deprivation (MD)-isolation in 1-2- and 7-8-day-old Wistar rats (P1,2 and P7,8 respectively, ages comparable to preterm and full-term human babies) on basal pain and pain sensitivity in conditions of inflammatory pain (formalin test) during adolescence. The neonatal impacts were: pain (formalin injection, FOR in the paw), stress (a short 60-min MD), or pain+stress combination (FOR+MD), and appropriate controls. We found that stress of short-term maternal deprivation-isolation and inflammatory pain on P1,2 and P7,8 significantly increased the vulnerability of the nociceptive system to inflammatory pain. Maternal deprivation-isolation on P1,2 as compared with a similar impact on P7,8 had a greater effect on pain sensitivity of the adolescent rats, but the influence of early pain was independent of the injury age. Only adolescent rats with an early combination of pain and maternal deprivation-isolation showed hypoalgesia in the hot plate (HP) test. However licking duration (reflecting pain sensitivity) in these rats did not exceed licking duration in animals exposed only to maternal deprivation-isolation or pain. This study adds new data to the growing body of work demonstrating that early noxious impacts have long-term consequences for the functional activity of the nociceptive system. Our new findings may help to understand the impact of pain and maternal separation in the neonatal intensive care unit.

Effects of intravenous propranolol on heat pain sensitivity in healthy men.

PubMed

Schweinhardt, P; Abulhasan, Y B; Koeva, V; Balderi, T; Kim, D J; Alhujairi, M; Carli, F

2013-05-01

Clinical studies have shown opioid-sparing effects of β-adrenergic antagonists perioperatively and β-blockers are being investigated for chronic musculoskeletal pain. However, the direct analgesic effects of β-blockers have rarely been examined in healthy humans. In a randomized, counter-balanced, double-blind, within-subject crossover design, we tested the effect of the lipophilic β-blocker propranolol (0.035 mg/kg body weight i.v.) on heat pain sensitivity in 39 healthy males, compared with placebo. To test for peripheral versus central effects, the peripherally acting β-blocker sotalol was also examined. Experimental stimuli were brief superficial noxious heat stimuli applied to the volar forearm. Non-painful cold stimuli were included to test for specificity. Sedation, mood and anxiety were assessed to investigate potential mechanisms underlying any analgesic effect. β-blocker effects on blood pressure were incorporated into the analysis because of a known inverse relationship between pain sensitivity and systolic blood pressure. Propranolol significantly decreased perceived intensity of heat pain stimuli but only in participants with small propranolol-induced blood pressure decreases. Even in this group, the effect was small (4%). Propranolol did not influence perceived intensity of non-noxious stimuli and had no effect on sedation, anxiety or mood. Sotalol did not influence heat pain sensitivity. Propranolol decreased pain sensitivity but its analgesic effects were small and counteracted by blood pressure decreases. The analgesic effects were not mediated by peripheral β-receptor blockade, sedation, mood or anxiety. The small effect indicates that the utility of β-blockers for clinical pain must be related to factors that do not play a significant role for experimental pain. © 2012 European Federation of International Association for the Study of Pain Chapters.

Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery

PubMed Central

Muraoka, Wataru; Nishizawa, Daisuke; Fukuda, Kenichi; Kasai, Shinya; Hasegawa, Junko; Wajima, Koichi; Nakagawa, Taneaki

2016-01-01

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment. PMID:28256933

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis).

PubMed

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C; Sarantopoulos, Konstantinos D; Yosipovitch, Gil

2017-08-01

To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity.

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis)

PubMed Central

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C.; Sarantopoulos, Konstantinos D.; Yosipovitch, Gil

2017-01-01

Purpose To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. Methods A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. Results The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Conclusions Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity. PMID:29391860

Pain Sensitivity Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case Control Study

PubMed Central

Greenspan, Joel D.; Slade, Gary D.; Bair, Eric; Dubner, Ronald; Fillingim, Roger B.; Ohrbach, Richard; Knott, Charlie; Mulkey, Flora; Rothwell, Rebecca; Maixner, William

2011-01-01

Many studies report that people with temporomandibular disorders (TMD) are more sensitive to experimental pain stimuli than TMD-free controls. Such differences in sensitivity are observed in remote body sites as well as in the orofacial region, suggesting a generalized upregulation of nociceptive processing in TMD cases. This large case-control study of 185 adults with TMD and 1,633 TMD-free controls measured sensitivity to painful pressure, mechanical cutaneous, and heat stimuli, using multiple testing protocols. Based on an unprecedented 36 experimental pain measures, 28 showed statistically significantly greater pain sensitivity in TMD cases than controls. The largest effects were seen for pressure pain thresholds at multiple body sites and cutaneous mechanical pain threshold. The other mechanical cutaneous pain measures and many of the heat pain measures showed significant differences, but with lesser effect sizes. Principal component analysis (PCA) of the pain measures derived from 1,633 controls identified five components labeled: (1) heat pain ratings, (2) heat pain aftersensations and tolerance, (3) mechanical cutaneous pain sensitivity, (4) pressure pain thresholds, and (5) heat pain temporal summation. These results demonstrate that, compared to TMD-free controls, chronic TMD cases are more sensitive to many experimental noxious stimuli at extra-cranial body sites, and provides for the first time the ability to directly compare the case-control effect sizes of a wide range of pain sensitivity measures. PMID:22074753

Are measures of pain sensitivity associated with pain and disability at 12-month follow up in chronic neck pain?

PubMed

Moloney, Niamh; Beales, Darren; Azoory, Roxanne; Hübscher, Markus; Waller, Robert; Gibbons, Rebekah; Rebbeck, Trudy

2018-06-14

Pain sensitivity and psychosocial issues are prognostic of poor outcome in acute neck disorders. However, knowledge of associations between pain sensitivity and ongoing pain and disability in chronic neck pain are lacking. We aimed to investigate associations of pain sensitivity with pain and disability at the 12-month follow-up in people with chronic neck pain. The predictor variables were: clinical and quantitative sensory testing (cold, pressure); neural tissue sensitivity; neuropathic symptoms; comorbidities; sleep; psychological distress; pain catastrophizing; pain intensity (for the model explaining disability at 12 months only); and disability (for the model explaining pain at 12 months only). Data were analysed using uni- and multivariate regression models to assess associations with pain and disability at the 12-month follow-up (n = 64 at baseline, n = 51 at follow-up). Univariable associations between all predictor variables and pain and disability were evident (r > 0.3; p < 0.05), except for cold and pressure pain thresholds and cold sensitivity. For disability at the 12-month follow-up, 24.0% of the variance was explained by psychological distress and comorbidities. For pain at 12 months, 39.8% of the variance was explained primarily by baseline disability. Neither clinical nor quantitative measures of pain sensitivity were meaningfully associated with long-term patient-reported outcomes in people with chronic neck pain, limiting their clinical application in evaluating prognosis. Copyright © 2018 John Wiley & Sons, Ltd.

Increased Sensitivity to Thermal Pain and Reduced Subcutaneous Lidocaine Efficacy in Redheads

PubMed Central

Liem, Edwin B.; Joiner, Teresa V.; Tsueda, Kentaro; Sessler, Daniel I.

2005-01-01

Background: Anesthetic requirement in redheads is exaggerated, suggesting that redheads may be especially sensitive to pain. We therefore tested the hypotheses that women with natural red hair are more sensitive to pain, and that redheads are resistant to topical and subcutaneous lidocaine. Methods: We evaluated pain sensitivity in red-haired (n=30) or dark-haired (n=30) women by determining the electrical current perception threshold, pain perception, and maximum pain tolerance with a Neurometer CPT/C (Neurotron, Inc., Baltimore, MD). We evaluated the analogous warm and cold temperature thresholds with the TSA-II Neurosensory Analyzer (Medoc Ltd., Minneapolis, MN). Volunteers were tested with both devices at baseline and with the Neurometer after 1-hour exposure to 4% liposomal lidocaine and after subcutaneous injection of 1% lidocaine. Data are presented as medians [interquartile ranges]. Results: Current perception, pain perception, and pain tolerance thresholds were similar in the red-haired and dark-haired women at 2000, 250, and 5 Hz. In contrast, redheads were more sensitive to cold pain perception (22.6°C [15.1, 26.1] vs. 12.6°C [0, 20], P=0.004), cold pain tolerance (6.0°C [0, 9.7] vs. 0.0°C [0.0, 2.0], P=0.001), and heat pain (46.3°C [45.7, 47.5] vs. 47.7°C [46.6, 48.7], P=0.009). Subcutaneous, lidocaine was significantly less effective in redheads, e.g., pain tolerance threshold at 2000 Hz stimulation in redheads was 11.0 mA [8.5, 16.5] vs. >20.0 mA [14.5, >20] in others, P=0.005). Conclusion: Red hair is the phenotype for mutations of the melanocortin 1 receptor. Our results indicate that redheads are more sensitive to thermal pain and are resistant to the analgesic effects of subcutaneous lidocaine. Mutations of the melanocortin 1 receptor, or a consequence thereof, thus modulate pain sensitivity. PMID:15731586

Abnormal Pain Modulation in Patients with Spatially Distributed Chronic Pain: Fibromyalgia

PubMed Central

Staud, Roland

2009-01-01

Many chronic pain syndromes including fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome, migraine headache, chronic back pain, and complex regional pain syndrome are associated with hypersensitivity to painful stimuli and with reduced endogenous pain inhibition. These findings suggest that modulation of pain-related information may be related to the onset and/or maintenance of chronic pain. Although pain sensitivity and pain inhibition are normally distributed in the general population, they are not useful as reliable predictors of future pain. The combination of heightened pain sensitivity and reduced pain-inhibition, however, appears to predispose individuals to greater risk for increased acute clinical pain (e.g., postoperative pain). It is unknown at this time whether such pain processing abnormalities may also place individuals at increased risk for chronic pain. Psychophysical methods, including heat sensory and pressure pain testing have become increasingly available and can be used for the evaluation of pain sensitivity and pain inhibition. However, long-term prospective studies in the general population are lacking which could yield insight into the role of heightened pain sensitivity and pain disinhibition for the development of chronic pain disorders like fibromyalgia. PMID:19647141

Streamlining the Evaluation of Low Back Pain in Children

PubMed Central

Auerbach, Joshua D.; Ahn, Jaimo; Zgonis, Miltiadis H.; Reddy, Sudheer C.; Ecker, Malcolm L.

2008-01-01

The workup of low back pain in children often results in overimaging so as not to miss organic back pain. The primary goal of this study was to identify which combination of imaging modalities provides the most sensitive and specific screening protocol for children with low back pain. Medical records from 100 consecutive patients between 2 and 18 years of age presenting with low back pain, without night pain or constitutional symptoms, were evaluated. A hyperextension test combined with a radiograph showed a negative predictive value of 0.81 and sensitivity of 0.90. The addition of a bone scan was highly effective in achieving good negative predictive value and sensitivity. Bone scans had perfect negative predictive value and sensitivity when symptom duration was less than 6 weeks. We identified a set of factors that is highly predictive for distinguishing organic back pain from mechanical back pain. Painless hyperextension combined with negative anteroposterior, lateral, and oblique lumbar radiographs and magnetic resonance images predicts mechanical back pain. For patients with nonneurologic back pain of less than 6 weeks duration, bone scan is the most useful screening test because it is accurate, accessible, inexpensive, and unlikely to require sedation. Level of Evidence: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18553213

A longitudinal study of pain, personality, and brain plasticity following peripheral nerve injury.

PubMed

Goswami, Ruma; Anastakis, Dimitri J; Katz, Joel; Davis, Karen D

2016-03-01

We do not know precisely why pain develops and becomes chronic after peripheral nerve injury (PNI), but it is likely due to biological and psychological factors. Here, we tested the hypotheses that (1) high Pain Catastrophizing Scale (PCS) scores at the time of injury and repair are associated with pain and cold sensitivity after 1-year recovery and (2) insula gray matter changes reflect the course of injury and improvements over time. Ten patients with complete median and/or ulnar nerve transections and surgical repair were tested ∼3 weeks after surgical nerve repair (time 1) and ∼1 year later for 6 of the 10 patients (time 2). Patients and 10 age-/sex-matched healthy controls completed questionnaires that assessed pain (patients) and personality and underwent quantitative sensory testing and 3T MRI to assess cortical thickness. In patients, pain intensity and neuropathic pain correlated with pain catastrophizing. Time 1 pain catastrophizing trended toward predicting cold pain thresholds at time 2, and at time 1 cortical thickness of the right insula was reduced. At time 2, chronic pain was related to the time 1 pain-PCS relationship and cold sensitivity, pain catastrophizing correlated with cold pain threshold, and insula thickness reversed to control levels. This study highlights the interplay between personality, sensory function, and pain in patients following PNI and repair. The PCS-pain association suggests that a focus on affective or negative components of pain could render patients vulnerable to chronic pain. Cold sensitivity and structural insula changes may reflect altered thermosensory or sensorimotor awareness representations.

The role of chronic psychosocial stress in explaining racial differences in stress reactivity and pain sensitivity

PubMed Central

Gordon, Jennifer L.; Johnson, Jacqueline; Nau, Samantha; Mechlin, Beth; Girdler, Susan S.

2016-01-01

Objective To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. Methods Participants included 133 AA and non-Hispanic White (nHW) individuals (mean (SD) age = 37 (9)) matched for age, sex and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. Results Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g. r = −.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. Conclusion Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs’ increased pain sensitivity in laboratory settings. PMID:27669431

The Role of Chronic Psychosocial Stress in Explaining Racial Differences in Stress Reactivity and Pain Sensitivity.

PubMed

Gordon, Jennifer L; Johnson, Jacqueline; Nau, Samantha; Mechlin, Beth; Girdler, Susan S

To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. Participants included 133 AA and non-Hispanic white (nHW) individuals (mean [SD] age, 37 [9]) matched for age, sex, and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g., r = -.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs' increased pain sensitivity in laboratory settings.

Pain sensitivity profiles in patients with advanced knee osteoarthritis

PubMed Central

Frey-Law, Laura A.; Bohr, Nicole L.; Sluka, Kathleen A.; Herr, Keela; Clark, Charles R.; Noiseux, Nicolas O.; Callaghan, John J; Zimmerman, M Bridget; Rakel, Barbara A.

2016-01-01

The development of patient profiles to subgroup individuals on a variety of variables has gained attention as a potential means to better inform clinical decision-making. Patterns of pain sensitivity response specific to quantitative sensory testing (QST) modality have been demonstrated in healthy subjects. It has not been determined if these patterns persist in a knee osteoarthritis population. In a sample of 218 participants, 19 QST measures along with pain, psychological factors, self-reported function, and quality of life were assessed prior to total knee arthroplasty. Component analysis was used to identify commonalities across the 19 QST assessments to produce standardized pain sensitivity factors. Cluster analysis then grouped individuals that exhibited similar patterns of standardized pain sensitivity component scores. The QST resulted in four pain sensitivity components: heat, punctate, temporal summation, and pressure. Cluster analysis resulted in five pain sensitivity profiles: a “low pressure pain” group, an “average pain” group, and three “high pain” sensitivity groups who were sensitive to different modalities (punctate, heat, and temporal summation). Pain and function differed between pain sensitivity profiles, along with sex distribution; however no differences in OA grade, medication use, or psychological traits were found. Residualizing QST data by age and sex resulted in similar components and pain sensitivity profiles. Further, these profiles are surprisingly similar to those reported in healthy populations suggesting that individual differences in pain sensitivity are a robust finding even in an older population with significant disease. PMID:27152688

Morning Versus Evening Bright Light Treatment at Home to Improve Function and Pain Sensitivity for Women with Fibromyalgia: A Pilot Study.

PubMed

Burgess, Helen J; Park, Margaret; Ong, Jason C; Shakoor, Najia; Williams, David A; Burns, John

2017-01-01

To test the feasibility, acceptability, and effects of a home-based morning versus evening bright light treatment on function and pain sensitivity in women with fibromyalgia. A single blind randomized study with two treatment arms: 6 days of a 1 hour morning light treatment or 6 days of a 1 hour evening light treatment. Function, pain sensitivity, and circadian timing were assessed before and after treatment. Participants slept at home, except for two nights in Sleep Center. Ten women meeting the American College of Rheumatology's diagnostic criteria for fibromyalgia, including normal blood test results. Self-reported function was assessed with the Fibromyalgia Impact Questionnaire (FIQ). Pain sensitivity was assessed using a heat stimulus that gave measures of threshold and tolerance. Circadian timing was assessed with the dim light melatonin onset. Both morning and evening light treatments led to improvements in function and pain sensitivity. However, only the morning light treatment led to a clinically meaningful improvement in function (>14% reduction from baseline FIQ) and morning light significantly increased pain threshold more than evening light ( P  < 0.05). Phase advances in circadian timing were associated with an increase in pain tolerance (r = 0.67, P  < 0.05). Bright light treatment appears to be a feasible and acceptable adjunctive treatment to women with fibromyalgia. Those who undergo morning light treatment may show improvements in function and pain sensitivity. Advances in circadian timing may be one mechanism by which morning light improves pain sensitivity. Findings can inform the design of a randomized controlled trial. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

SLOWLY REPEATED EVOKED PAIN (SREP) AS A MARKER OF CENTRAL SENSITIZATION IN FIBROMYALGIA: DIAGNOSTIC ACCURACY AND RELIABILITY IN COMPARISON WITH TEMPORAL SUMMATION OF PAIN.

PubMed

de la Coba, Pablo; Bruehl, Stephen; Gálvez-Sánchez, Carmen María; Reyes Del Paso, Gustavo A

2018-05-01

This study examined the diagnostic accuracy and test-retest reliability of a novel dynamic evoked pain protocol (slowly repeated evoked pain; SREP) compared to temporal summation of pain (TSP), a standard index of central sensitization. Thirty-five fibromyalgia (FM) and 30 rheumatoid arthritis (RA) patients completed, in pseudorandomized order, a standard mechanical TSP protocol (10 stimuli of 1s duration at the thenar eminence using a 300g monofilament with 1s interstimulus interval) and the SREP protocol (9 suprathreshold pressure stimuli of 5s duration applied to the fingernail with a 30s interstimulus interval). In order to evaluate reliability for both protocols, they were repeated in a second session 4-7 days later. Evidence for significant pain sensitization over trials (increasing pain intensity ratings) was observed for SREP in FM (p<.001) but not in RA (p=.35), whereas significant sensitization was observed in both diagnostic groups for the TSP protocol (p's<.008). Compared to TSP, SREP demonstrated higher overall diagnostic accuracy (87.7% vs. 64.6%), greater sensitivity (0.89 vs. 0.57), and greater specificity (0.87 vs. 0.73) in discriminating between FM and RA patients. Test-retest reliability of SREP sensitization was good in FM (ICCs: 0.80), and moderate in RA (ICC: 0.68). SREP seems to be a dynamic evoked pain index tapping into pain sensitization that allows for greater diagnostic accuracy in identifying FM patients compared to a standard TSP protocol. Further research is needed to study mechanisms underlying SREP and the potential utility of adding SREP to standard pain evaluation protocols.

Pain sensitivity mediates the relationship between stress and headache intensity in chronic tension-type headache.

PubMed

Cathcart, Stuart; Bhullar, Navjot; Immink, Maarten; Della Vedova, Chris; Hayball, John

2012-01-01

A central model for chronic tension-type headache (CTH) posits that stress contributes to headache, in part, by aggravating existing hyperalgesia in CTH sufferers. The prediction from this model that pain sensitivity mediates the relationship between stress and headache activity has not yet been examined. To determine whether pain sensitivity mediates the relationship between stress and prospective headache activity in CTH sufferers. Self-reported stress, pain sensitivity and prospective headache activity were measured in 53 CTH sufferers recruited from the general population. Pain sensitivity was modelled as a mediator between stress and headache activity, and tested using a nonparametric bootstrap analysis. Pain sensitivity significantly mediated the relationship between stress and headache intensity. The results of the present study support the central model for CTH, which posits that stress contributes to headache, in part, by aggravating existing hyperalgesia in CTH sufferers. Implications for the mechanisms and treatment of CTH are discussed.

Clinical descriptors for the recognition of central sensitization pain in patients with knee osteoarthritis.

PubMed

Lluch, Enrique; Nijs, Jo; Courtney, Carol A; Rebbeck, Trudy; Wylde, Vikki; Baert, Isabel; Wideman, Timothy H; Howells, Nick; Skou, Søren T

2017-08-02

Despite growing awareness of the contribution of central pain mechanisms to knee osteoarthritis pain in a subgroup of patients, routine evaluation of central sensitization is yet to be incorporated into clinical practice. The objective of this perspective is to design a set of clinical descriptors for the recognition of central sensitization in patients with knee osteoarthritis that can be implemented in clinical practice. A narrative review of original research papers was conducted by nine clinicians and researchers from seven different countries to reach agreement on clinically relevant descriptors. It is proposed that identification of a dominance of central sensitization pain is based on descriptors derived from the subjective assessment and the physical examination. In the former, clinicians are recommended to inquire about intensity and duration of pain and its association with structural joint changes, pain distribution, behavior of knee pain, presence of neuropathic-like or centrally mediated symptoms and responsiveness to previous treatment. The latter includes assessment of response to clinical test, mechanical hyperalgesia and allodynia, thermal hyperalgesia, hypoesthesia and reduced vibration sense. This article describes a set of clinically relevant descriptors that might indicate the presence of central sensitization in patients with knee osteoarthritis in clinical practice. Although based on research data, the descriptors proposed in this review require experimental testing in future studies. Implications for Rehabilitation Laboratory evaluation of central sensitization for people with knee osteoarthritis is yet to be incorporated into clinical practice. A set of clinical indicators for the recognition of central sensitization in patients with knee osteoarthritis is proposed. Although based on research data, the clinical indicators proposed require further experimental testing of psychometric properties.

Impact of early developmental fluoride exposure on the peripheral pain sensitivity in mice.

PubMed

Ma, Jing; Liu, Fei; Liu, Peng; Dong, Ying-Ying; Chu, Zheng; Hou, Tie-Zhou; Dang, Yong-Hui

2015-12-01

Consumption of high concentration of fluoride in the drinking water would cause the fluorosis and chronic pain. Similar pain syndrome appeared in the patients in fluoride therapy of osteoporotic. The aim of the current study was to examine whether exposing immature mice to fluoride would modify the peripheral pain sensitivity or even cause a pain syndrome. We gave developmental fluoride exposure to mice in different concentration (0mg/L, 50mg/L and 100mg/L) and evaluated their basal pain threshold. Von Frey hair test, hot plate test and formalin test were conducted to examine the mechanical, thermal nociceptive threshold and inflammatory pain, respectively. In addition, the expression of hippocampal brain-derived neurotrophic factor (BDNF) was also evaluated by Western blotting. Hyperalgesia in fluoride exposure mice was exhibited in the Von Frey hair test, hot plate test and formalin test. Meanwhile, the expression of BDNF was significantly higher than that of control group. The results suggest that early developmental fluoride exposure may lower the basal pain threshold and be associated with the increasing of BDNF expression in hippocampus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

PubMed

Di Stefano, G; Celletti, C; Baron, R; Castori, M; Di Franco, M; La Cesa, S; Leone, C; Pepe, A; Cruccu, G; Truini, A; Camerota, F

2016-09-01

Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain. © 2016 European Pain Federation - EFIC®

Increased thermal pain sensitivity in animals exposed to chronic high dose Vicodin but not pure hydrocodone.

PubMed

O'Connell, Thomas F; Carpenter, Patrick S; Caballero, Nadia; Putnam, Andrew J; Steere, Joshua T; Matz, Gregory J; Foecking, Eileen M

2014-01-01

Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one of the most prescribed drugs on the market today. Opioids have demonstrated the ability to paradoxically cause increased pain sensitivity to users in a phenomena called opioid-induced hyperalgesia (OIH). While selected opioids have been shown to produce OIH symptoms in an animal model, hydrocodone and the combination drug Vicodin have yet to be studied. The purpose of this study was to explore the effect of exposure to chronic high dose Vicodin or its components on the sensitivity to both thermal and mechanical pain. Animals were randomly divided into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and administered the drug daily for 120 days. Rats were subsequently tested for thermal and mechanical sensitivity. The rats in the Vicodin group displayed a significant decrease in withdrawal time to thermal pain. The rats receiving acetaminophen, hydrocodone, and vehicle showed no statistically significant hypersensitivity in thermal testing. None of the groups demonstrated statistically significant hypersensitivity to mechanical testing. The data suggests Vicodin produces signs of OIH in a rodent model. However, increased pain sensitivity was only noted in the thermal pathway and the hypersensitivity was only seen with the opioid combination drug, not the opioid alone. The results of this study both support the results of previous rodent opioid studies while generating further questions about the specific properties of Vicodin that contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic pain necessitates further research looking into this paradoxical pain response.

Enhanced Area of Secondary Hyperalgesia in Women with Multiple Stressful Life Events: A Pilot Study.

PubMed

You, Dokyoung S; Creech, Suzannah K; Meagher, Mary W

2016-10-01

Stressful life events are associated with increased pain severity and chronicity. However, the mechanism underlying this association remains disputed. Recent animal studies suggest that chronic stress increases pain sensitivity and persistence by enhancing peripheral and central sensitization mechanisms. To test this hypothesis in humans, the authors examined whether sensitization is enhanced in healthy women reporting more stressful life events using the topical capsaicin test. Thirty-two healthy young women reporting varying levels of stressful life events were invited for laboratory pain testing. Capsaicin was applied topically to the volar forearm. Measurements included capsaicin-induced spontaneous pain and area of secondary hyperalgesia in the region surrounding capsaicin application. Physiological (heart rate and skin conductance) and self-reported affective (emotional valence and arousal) states were also measured. The results indicate that more stressful life events predicted a linear increase in the area of secondary hyperalgesia (β = 0.40, p = 0.023, R 2 = 0.16), but not the intensity of secondary hyperalgesia nor capsaicin-induced spontaneous pain. These findings suggest that life stressors may be associated with heightened central sensitization manifested by an increased area of secondary hyperalgesia. Additionally, life stressors were related to greater sympathetic cardiac, but not to affective responses to capsaicin-induced pain. This study shows that women reporting more stressful life events show a larger area of secondary mechanical hyperalgesia. These preliminary findings suggest that life stressors may facilitate pain processing by enhancing central sensitization. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Do pain-associated contexts increase pain sensitivity? An investigation using virtual reality.

PubMed

Harvie, Daniel S; Sterling, Michele; Smith, Ashley D

2018-04-30

Pain is not a linear result of nociception, but is dependent on multisensory inputs, psychological factors, and prior experience. Since nociceptive models appear insufficient to explain chronic pain, understanding non-nociceptive contributors is imperative. Several recent models propose that cues associatively linked to painful events might acquire the capacity to augment, or even cause, pain. This experiment aimed to determine whether contexts associated with pain, could modulate mechanical pain thresholds and pain intensity. Forty-eight healthy participants underwent a contextual conditioning procedure, where three neutral virtual reality contexts were paired with either unpredictable noxious stimulation, unpredictable vibrotactile stimulation, or no stimulation. Following the conditioning procedure, mechanical pain thresholds and pain evoked by a test stimulus were examined in each context. In the test phase, the effect of expectancy was equalised across conditions by informing participants when thresholds and painful stimuli would be presented. Contrary to our hypothesis, scenes that were associated with noxious stimulation did not increase mechanical sensitivity (p=0.08), or increase pain intensity (p=0.46). However, an interaction with sex highlighted the possibility that pain-associated contexts may alter pain sensitivity in females but not males (p=0.03). Overall, our data does not support the idea that pain-associated contexts can alter pain sensitivity in healthy asymptomatic individuals. That an effect was shown in females highlights the possibility that some subgroups may be susceptible to such an effect, although the magnitude of the effect may lack real-world significance. If pain-associated cues prove to have a relevant pain augmenting effect, in some subgroups, procedures aimed at extinguishing pain-related associations may have therapeutic potential.

Differences in Clinical Pain and Experimental Pain Sensitivity Between Asian Americans and Whites With Knee Osteoarthritis.

PubMed

Ahn, Hyochol; Weaver, Michael; Lyon, Debra E; Kim, Junglyun; Choi, Eunyoung; Staud, Roland; Fillingim, Roger B

2017-02-01

Ethnicity has been associated with clinical and experimental pain responses. Whereas ethnic disparities in pain in other minority groups compared with whites are well described, pain in Asian Americans remains poorly understood. The purpose of this study was to characterize differences in clinical pain intensity and experimental pain sensitivity among older Asian American and non-Hispanic white (NHW) participants with knee osteoarthritis (OA). Data were collected from 50 Asian Americans ages 45 to 85 (28 Korean, 9 Chinese, 7 Japanese, 5 Filipino, and 1 Indian) and compared with 50 age-matched and sex-matched NHW individuals with symptomatic knee OA pain. The Western Ontario and McMaster Universities Osteoarthritis Index and Graded Chronic Pain Scale were used to assess the intensity of clinical knee pain. In addition, quantitative sensory testing was used to measure experimental sensitivity to heat-induced and mechanically induced pain. Asian American participants had significantly higher levels of clinical pain intensity than NHW participants with knee OA. In addition, Asian American participants had significantly higher experimental pain sensitivity than NHW participants with knee OA. These findings add to the growing literature regarding ethnic and racial differences in clinical pain intensity and experimental pain sensitivity. Asian Americans in particular may be at risk for clinical pain and heightened experimental pain sensitivity. Further investigation is needed to identify the mechanisms underlying ethnic group differences in pain between Asian Americans and NHWs, and to ensure that ethnic group disparities in pain are ameliorated.

Salivary Cortisol and Cold Pain Sensitivity in Female Twins

PubMed Central

Godfrey, Kathryn M; Strachan, Eric; Dansie, Elizabeth; Crofford, Leslie J; Buchwald, Dedra; Goldberg, Jack; Poeschla, Brian; Succop, Annemarie; Noonan, Carolyn; Afari, Niloofar

2013-01-01

Background There is a dearth of knowledge about the link between cortisol and pain sensitivity. Purpose We examined the association of salivary cortisol with indices of cold pain sensitivity in 198 female twins and explored the role of familial confounding. Methods Three-day saliva samples were collected for cortisol levels and a cold pressor test was used to collect pain ratings and time to threshold and tolerance. Linear regression modeling with generalized estimating equations examined the overall and within-pair associations. Results Lower diurnal variation of cortisol was associated with higher pain ratings at threshold (p = 0.02) and tolerance (p < 0.01). The relationship of diurnal variation with pain ratings at threshold and tolerance was minimally influenced by familial factors (i.e., genetics and common environment). Conclusions Understanding the genetic and non-genetic mechanisms underlying the link between HPA axis dysregulation and pain sensitivity may help to prevent chronic pain development and maintenance. PMID:23955075

Quantitative sensory testing somatosensory profiles in patients with cervical radiculopathy are distinct from those in patients with nonspecific neck-arm pain.

PubMed

Tampin, Brigitte; Slater, Helen; Hall, Toby; Lee, Gabriel; Briffa, Noelle Kathryn

2012-12-01

The aim of this study was to establish the somatosensory profiles of patients with cervical radiculopathy and patients with nonspecific neck-arm pain associated with heightened nerve mechanosensitivity (NSNAP). Sensory profiles were compared to healthy control (HC) subjects and a positive control group comprising patients with fibromyalgia (FM). Quantitative sensory testing (QST) of thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimulation was performed in the maximal pain area, the corresponding dermatome and foot of 23 patients with painful C6 or C7 cervical radiculopathy, 8 patients with NSNAP in a C6/7 dermatomal pain distribution, 31 HC and 22 patients with FM. For both neck-arm pain groups, all QST parameters were within the 95% confidence interval of HC data. Patients with cervical radiculopathy were characterised by localised loss of function (thermal, mechanical, vibration detection P<.009) in the maximal pain area and dermatome (thermal detection, vibration detection, pressure pain sensitivity P<.04), consistent with peripheral neuronal damage. Both neck-arm pain groups demonstrated increased cold sensitivity in their maximal pain area (P<.03) and the foot (P<.009), and this was also the dominant sensory characteristic in patients with NSNAP. Both neck-arm pain groups differed from patients with FM, the latter characterised by a widespread gain of function in most nociceptive parameters (thermal, pressure, mechanical pain sensitivity P<.027). Despite commonalities in pain characteristics between the 2 neck-arm pain groups, distinct sensory profiles were demonstrated for each group. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Can Anxiety Tested in the Elevated Plus-maze Be Related to Nociception Sensitivity in Adult Male Rats?

PubMed

Pometlová, Marie; Yamamotová, Anna; Nohejlová, Kateryna; Šlamberová, Romana

Methamphetamine (MA) is one of the most addictive psychostimulant drugs with a high potential for abuse. Our previous studies demonstrated that MA administered to pregnant rats increases pain sensitivity and anxiety in their adult offspring and makes them more sensitive to acute administration of the same drug in adulthood. Because individuals can differ considerably in terms of behaviour and physiology, such as rats that do not belong in some characteristics (e.g. anxiety) to average, can be described as low-responders or high-responders, are then more or less sensitive to pain. Therefore, prenatally MA-exposed adult male rats treated in adulthood with a single dose of MA (1 mg/ml/kg) or saline (1 ml/kg) were tested in the present study. We examined the effect of acute MA treatment on: (1) the anxiety in the Elevated plus-maze (EPM) test and memory in EPM re-test; (2) nociception sensitivity in the Plantar test; (3) the correlation between the anxiety, memory and the nociception. Our results demonstrate that: (1) MA has an anxiogenic effect on animals prenatally exposed to the same drug in the EPM; (2) all the differences induced by acute MA treatment disappeared within the time of 48 hours; (3) there was no effect of MA on nociception per se, but MA induced higher anxiety in individuals less sensitive to pain than in animals more sensitive to pain. In conclusion, the present study demonstrates unique data showing association between anxiety and nociceptive sensitivity of prenatally MA-exposed rats that is induced by acute drug administration.

Decreased low back pain intensity and differential gene expression following Calmare®: results from a double-blinded randomized sham-controlled study.

PubMed

Starkweather, Angela R; Coyne, Patrick; Lyon, Debra E; Elswick, R K; An, Kyungeh; Sturgill, Jamie

2015-02-01

In this double-blinded, randomized controlled trial we evaluated the effects of Calmare®, a non-invasive neurocutaneous electrical pain intervention, on lower back pain intensity as measured by the "worst" pain score and on pain interference using the Brief Pain Inventory-Short Form, on measures of pain sensitivity assessed by quantitative sensory testing, and on mRNA expression of pain sensitivity genes. Thirty participants were randomized to receive up to 10 sessions of Calmare® treatment (n = 15) or a sham treatment (n = 15) using the same device at a non-therapeutic threshold. At 3 weeks after conclusion of treatment, compared with the sham group, the Calmare® group reported a significant decrease in the "worst" pain and interference scores. There were also significant differences in pain sensitivity and differential mRNA expression of 17 pain genes, suggesting that Calmare® can be effective in reducing pain intensity and interference in individuals with persistent low back pain by altering the mechanisms of enhanced pain sensitivity. Further study of long-term pain outcomes, particularly functional status, analgesic use and health care utilization, is warranted. © 2015 Wiley Periodicals, Inc.

Differences in Clinical Pain and Experimental Pain Sensitivity between Asian Americans and Whites with Knee Osteoarthritis

PubMed Central

Ahn, Hyochol; Weaver, Michael; Lyon, Debra; Kim, Junglyun; Choi, Eunyoung; Staud, Roland; Fillingim, Roger B.

2016-01-01

Objective Ethnicity has been associated with clinical and experimental pain responses. While ethnic disparities in pain in other minority groups compared to whites are well described, pain in Asian Americans remains poorly understood. The purpose of this study was to characterize differences in clinical pain intensity and experimental pain sensitivity among older Asian American and non-Hispanic White (NHW) participants with knee osteoarthritis (OA). Methods Data were collected from 50 Asian Americans ages 45-85 (28 Korean, 9 Chinese, 7 Japanese, 5 Filipino, and 1 Indian) and compared to 50 age- and gender-matched NHW individuals with symptomatic knee OA pain. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Graded Chronic Pain Scale (GCPS) were used to assess the intensity of clinical knee pain. In addition, quantitative sensory testing was used to measure experimental sensitivity to heat- and mechanically-induced pain. Results Asian American participants had significantly higher levels of clinical pain intensity than NHW participants with knee OA. In addition, Asian American participants had significantly higher experimental pain sensitivity than NHW participants with knee OA. Discussion These findings add to the growing literature regarding ethnic and racial differences in clinical pain intensity and experimental pain sensitivity. Asian Americans in particular may be at risk for clinical pain and heightened experimental pain sensitivity. Further investigation is needed to identify the mechanisms underlying ethnic group differences in pain between Asian Americans and non-Hispanic Whites, and to ensure that ethnic group disparities in pain are ameliorated. PMID:28060784

Pain Sensitivity is Inversely Related to Regional Grey Matter Density in the Brain

PubMed Central

Emerson, Nichole M.; Zeidan, Fadel; Lobanov, Oleg V.; Hadsel, Morten S.; Martucci, Katherine T.; Quevedo, Alexandre S.; Starr, Christopher J.; Nahman-Averbuch, Hadas; Weissman-Fogel, Irit; Granovsky, Yelena; Yarnitsky, David; Coghill, Robert C.

2014-01-01

Pain is a highly personal experience that varies substantially among individuals. In search of an anatomical correlate of pain sensitivity we used voxel-based morphometry (VBM) to investigate the relationship between grey matter density across the whole brain and inter-individual differences in pain sensitivity in 116 healthy volunteers (62 females, 54 males). Structural MRI and psychophysical data from 10 previous fMRI studies were used. Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates. Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49°C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship. No regions exhibited a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure. PMID:24333778

Pain sensitivity mediates the relationship between stress and headache intensity in chronic tension-type headache

PubMed Central

Cathcart, Stuart; Bhullar, Navjot; Immink, Maarten; Della Vedova, Chris; Hayball, John

2012-01-01

BACKGROUND: A central model for chronic tension-type headache (CTH) posits that stress contributes to headache, in part, by aggravating existing hyperalgesia in CTH sufferers. The prediction from this model that pain sensitivity mediates the relationship between stress and headache activity has not yet been examined. OBJECTIVE: To determine whether pain sensitivity mediates the relationship between stress and prospective headache activity in CTH sufferers. METHOD: Self-reported stress, pain sensitivity and prospective headache activity were measured in 53 CTH sufferers recruited from the general population. Pain sensitivity was modelled as a mediator between stress and headache activity, and tested using a nonparametric bootstrap analysis. RESULTS: Pain sensitivity significantly mediated the relationship between stress and headache intensity. CONCLUSIONS: The results of the present study support the central model for CTH, which posits that stress contributes to headache, in part, by aggravating existing hyperalgesia in CTH sufferers. Implications for the mechanisms and treatment of CTH are discussed. PMID:23248808

Sensory focusing versus distraction and pain: moderating effects of anxiety sensitivity in males and females.

PubMed

Thompson, Trevor; Keogh, Edmund; French, Christopher C

2011-08-01

Although previous research has examined whether the relative effects of distraction and sensory focusing on pain are dependent upon anxiety sensitivity, such research has concentrated primarily on females. Given the increasing emergence of sex differences in pain processing, the current study aimed to examine whether any influence of anxiety sensitivity on coping effectiveness differs for males and females. The sample consisted of 76 healthy adults (41 males and 35 females), all of whom received distraction and sensory-focusing instructions and underwent noxious thermal testing (cold and heat). Results showed that anxiety sensitivity was positively associated with the emotional qualities of cold pain, and that males exhibited significantly greater heat pain tolerance than females. In addition, within males, a significant coping × anxiety sensitivity effect was found for cold tolerance, with distraction superior to sensory focusing only when anxiety sensitivity was high. In females, however, distraction was a superior strategy irrespective of anxiety sensitivity. This study highlights the importance of considering anxiety sensitivity and sex when examining the relative effectiveness of attentional pain coping strategies. This finding may be potentially beneficial to clinicians considering pain management interventions that include a cognitive or attentional component. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Pain Sensitivity and Recovery From Mild Chronic Sleep Loss

PubMed Central

Roehrs, Timothy A.; Harris, Erica; Randall, Surilla; Roth, Thomas

2012-01-01

Study Objectives: To determine whether an extended bedtime in sleepy and otherwise healthy volunteers would increase alertness and thereby also reduce pain sensitivity. Setting: Outpatient with sleep laboratory assessments. Participants and Interventions: Healthy volunteers (n = 18), defined as having an average daily sleep latency on the Multiple Sleep Latency Test (MSLT) < 8 min, were randomized to 4 nights of extended bedtime (10 hr) (EXT) or 4 nights of their diary-reported habitual bedtimes (HAB). On day 1 and day 4 they received a standard MSLT (10:00, 12:00, 14:00, and 16:00 hr) and finger withdrawal latency pain testing to a radiant heat stimulus (10:30 and 14:30 hr). Results: During the four experimental nights the EXT group slept 1.8 hr per night more than the HAB group and average daily sleep latency on the MSLT increased in the EXT group, but not the HAB group. Similarly, finger withdrawal latency was increased (pain sensitivity was reduced) in the EXT group but not the HAB group. The nightly increase in sleep time during the four experimental nights was correlated with the improvement in MSLT, which in turn was correlated with reduced pain sensitivity. Conclusions: These are the first data to show that an extended bedtime in mildly sleepy healthy adults, which resulted in increased sleep time and reduced sleepiness, reduces pain sensitivity. Citation: Roehrs TA; Harris E; Randall S; Roth T. Pain sensitivity and recovery from mild chronic sleep loss. SLEEP 2012;35(12):1667-1672. PMID:23204609

Pain Sensitization Associated with Non-Response Following Physiotherapy in People with Knee Osteoarthritis.

PubMed

O'Leary, Helen; Smart, Keith M; Moloney, Niamh A; Blake, Catherine; Doody, Catherine M

2018-05-22

In knee osteoarthritis (OA) pain sensitization has been linked to a more severe symptomatology, but the prognostic implications of pain sensitivity in people undergoing conservative treatment such as physiotherapy are not established. This study aimed to prospectively investigate the association between features of pain sensitization and clinical outcome (non-response) following guideline-based physiotherapy in people with knee OA. Participants (n=156) with moderate/severe knee OA were recruited from secondary care. All participants completed self-administered questionnaires and underwent quantitative sensory testing (QST) at baseline, thereby establishing subjective and objective measures of pain sensitization. Participants (n=134) were later classified following a physiotherapy intervention, using treatment responder criteria (responder/non-responder). QST data was reduced to a core set of latent variables using principal component analysis. A hierarchical logistic regression model was constructed to investigate if features related to pain sensitization predicted non-response after controlling for other known predictors of poor outcome in knee OA. Higher temporal summation (TS) (OR 2.00, 95% CI 1.23 to 3.27) and lower pressure pain thresholds (PPT) (OR 0.48, 95% CI 0.29 to 0.81) emerged as robust predictors of non-response following physiotherapy, along with a higher comorbidity score. The model demonstrated high sensitivity (87.8%) but modest specificity (52.3%). The independent relationship between pain sensitization and non-response may indicate an underlying explanatory association between neuroplastic changes in nociceptive processing and the maintenance of on-going pain and disability in knee OA pain. These preliminary results suggest interventions targeting pain sensitization may warrant future investigation in this population.

[Diagnostic test scale SI5: Assessment of sacroiliac joint dysfunction].

PubMed

Acevedo González, Juan C; Quintero Oliveros, Silvia

2015-01-01

Sacroiliac joint dysfunction is a known cause of low back pain. We think that a diagnostic score scale (SI5) may be performed to assess diagnostic utility of clinical signs of sacroiliac joint dysfunction. The primary aim of the present study was to conduct the pilot study of our new diagnostic score scale, the SI5, for sacroiliac joint syndrome. We reviewed the literature on clinical characteristics, diagnostic tests and imaging most commonly used in diagnosing sacroiliac joint dysfunction. Our group evaluated the diagnostic utility of these aspects and we used those considered most representative to develop the SI5 diagnostic scale. The SI5 scale was applied to 22 patients with low back pain; afterwards, the standard test for diagnosing this pathology (selective blockage of the SI joint) was also performed on these patients. The sensitivity and specificity for each sign were also assessed and the diagnostic scale called SI5 was then proposed, based on these data. The most sensitive clinical tests for diagnosing SI joint dysfunction were 2 patient-reported clinical characteristics, the Laguerre Test, sacroiliac rocking test and Yeomans test (greater than 80% sensitivity). The tests with greatest diagnostic specificity (>80%) were the Lewitt test, Piedallu test and Gillet test. The proposed SI5 test score scale showed sensitivity of 73% and specificity of 71%. Sacroiliac joint syndrome has been shown to produce low back pain frequently; however, the diagnostic value of examination tests for sacroiliac joint pain has been questioned by other authors. The pilot study on the SI5 diagnostic score scale showed good sensitivity and specificity. However, the process of statistical validation of the SI5 needs to be continued. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Pain sensitivity is inversely related to regional grey matter density in the brain.

PubMed

Emerson, Nichole M; Zeidan, Fadel; Lobanov, Oleg V; Hadsel, Morten S; Martucci, Katherine T; Quevedo, Alexandre S; Starr, Christopher J; Nahman-Averbuch, Hadas; Weissman-Fogel, Irit; Granovsky, Yelena; Yarnitsky, David; Coghill, Robert C

2014-03-01

Pain is a highly personal experience that varies substantially among individuals. In search of an anatomical correlate of pain sensitivity, we used voxel-based morphometry to investigate the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women, 54 men). Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used. Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates. Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49°C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship. No regions showed a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Pain facilitation and pain inhibition during conditioned pain modulation in fibromyalgia and in healthy controls.

PubMed

Potvin, Stéphane; Marchand, Serge

2016-08-01

Although fibromyalgia (FM) is associated with a deficit in inhibitory conditioned pain modulation (CPM), the discriminative power of CPM procedures is unknown. Moreover, the high intersubject heterogeneity in CPM responses in FM raises the possibility that a sizeable subgroup of these patients may experience pain facilitation during CPM, but the phenomenon has not been explicitly studied. To address these issues, 96 patients with FM and 71 healthy controls were recruited. Thermal stimuli were used to measure pain thresholds. Pain inhibition was elicited using a tonic thermal test (Peltier thermode) administered before and after activation of CPM mechanisms using a cold pressor test. Thermal pain thresholds were lower in patients with FM than in healthy controls. Pain ratings during the cold pressor test were higher in patients with FM, relative to controls. The CPM inhibitory efficacy was lower in patients with FM than in controls. The CPM procedure had good specificity (78.9%) but low sensitivity (45.7%), whereas a composite pain index had good sensitivity (75.0%) and specificity (78.9%). Finally, the rate of patients with FM who reported pain facilitation during the CPM procedure was found to be significantly increased compared with that of controls (41.7% vs 21.2%). The good discriminative power of the composite pain index highlights the need for further validation studies using mechanistically relevant psychophysical procedures in FM. The low sensitivity of the CPM procedure, combined with the large proportion of patients with FM experiencing pain facilitation during CPM, strongly suggests that endogenous pain inhibition mechanisms are deeply impaired in patients with FM, but only in a subgroup of them.

Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7.

PubMed

Helås, T; Sagafos, D; Kleggetveit, I P; Quiding, H; Jönsson, B; Segerdahl, M; Zhang, Z; Salter, H; Schmelz, M; Jørum, E

2017-09-01

Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity. Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n = 27) and controls (n = 25), neither did the dose-response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits Na V 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the Na V 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia. Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in Na V 1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance. Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the Na V 1.7 I848T mutation are normal and only nociceptor sensitivity to intradermal lidocaine is changed. Only in EM patients with mutations in Na V 1.7, 1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine sensitivity as compared to controls. © 2017 European Pain Federation - EFIC®.

Long-Term Effects of Neonatal Pain and Stress on Reactivity of the Nociceptive System.

PubMed

Butkevich, I P; Mikhailenko, V A

2016-10-01

The influence of inflammatory pain and/or weaning stress at different terms of neonatal development on functional activity of the nociceptive system during adulthood was studied in rats. Repeated stress in 1-2-day-old rat pups (a premature baby model) enhanced pain sensitivity to peripheral inflammation in both males and females. Repeated inflammatory pain experienced by male pups aged 1-2 or 7-8 days (models of preterm and full-term baby), even in presence of mother, enhanced pain behavior under conditions of repeated inflammatory pain in adulthood. Pain sensitivity in adult animals before (hot plate test) and after formation of the inflammatory focus (formalin test) depended on the age when the animals were subjected to the injury, type of exposure, and on animal sex. The priority data obtained by us will help to understand the mechanisms of long-term effects of early injuries and are important for pediatricians and neonatologists.

Pain-related anxiety influences pain perception differently in men and women: a quantitative sensory test across thermal pain modalities.

PubMed

Thibodeau, Michel A; Welch, Patrick G; Katz, Joel; Asmundson, Gordon J G

2013-03-01

The sexes differ with respect to perception of experimental pain. Anxiety influences pain perception more in men than in women; however, there lacks research exploring which anxiety constructs influence pain perception differentially between men and women. Furthermore, research examining whether depression is associated with pain perception differently between the sexes remains scant. The present investigation was designed to examine how trait anxiety, pain-related anxiety constructs (ie, fear of pain, pain-related anxiety, anxiety sensitivity), and depression are associated with pain perception between the sexes. A total of 95 nonclinical participants (55% women) completed measures assessing the constructs of interest and participated in quantitative sensory testing using heat and cold stimuli administered by a Medoc Pathway Pain and Sensory Evaluation System. The findings suggest that pain-related anxiety constructs, but not trait anxiety, are associated with pain perception. Furthermore, these constructs are associated with pain intensity ratings in men and pain tolerance levels in women. This contrasts with previous research suggesting that anxiety influences pain perception mostly or uniquely in men. Depression was not systematically associated with pain perception in either sex. Systematic relationships were not identified that allow conclusions regarding how fear of pain, pain-related anxiety, and anxiety sensitivity may contribute to pain perception differentially in men and women; however, anxiety sensitivity was associated with increased pain tolerance, a novel finding needing further examination. The results provide directions for future research and clinical endeavors and support that fear and anxiety are important features associated with hyperalgesia in both men and women. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Experimental pain in the groin may refer into the lower abdomen: Implications to clinical assessments.

PubMed

Drew, M K; Palsson, T S; Hirata, R P; Izumi, M; Lovell, G; Welvaert, M; Chiarelli, P; Osmotherly, P G; Graven-Nielsen, T

2017-10-01

To investigate the effects of experimental adductor pain on the pain referral pattern, mechanical sensitivity and muscle activity during common clinical tests. Repeated-measures design. In two separate sessions, 15 healthy males received a hypertonic (painful) and isotonic (control) saline injection to either the adductor longus (AL) tendon to produce experimental groin pain or into the rectus femoris (RF) tendon as a painful control. Pain intensity was recorded on a visual analogue scale (VAS) with pain distribution indicated on body maps. Pressure pain thresholds (PPT) were assessed bilaterally in the groin area. Electromyography (EMG) of relevant muscles was recorded during six provocation tests. PPT and EMG assessment were measured before, during and after experimental pain. Hypertonic saline induced higher VAS scores than isotonic saline (p<0.001), and a local pain distribution in 80% of participants. A proximal pain referral to the lower abdominal region in 33% (AL) and 7% (RF) of participants. Experimental pain (AL and RF) did not significantly alter PPT values or the EMG amplitude in groin or trunk muscles during provocation tests when forces were matched with baseline. This study demonstrates that AL tendon pain was distributed locally in the majority of participants but may refer to the lower abdomen. Experimental adductor pain did not significantly alter the mechanical sensitivity or muscle activity patterns. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Sex moderates the effects of positive and negative affect on clinical pain in patients with knee osteoarthritis.

PubMed

Speed, Traci J; Richards, Jessica M; Finan, Patrick H; Smith, Michael T

2017-07-01

Sex differences in clinical pain severity and response to experimental pain are commonly reported, with women generally showing greater vulnerability. Affect, including state (a single rating) and stable (average daily ratings over two weeks) positive affect and negative affect has also been found to impact pain sensitivity and severity, and research suggests that affect may modulate pain differentially as a function of sex. The current study aimed to examine sex as a moderator of the relationships between affect and pain-related outcomes among participants with knee osteoarthritis (KOA). One hundred and seventy-nine participants (59 men) with KOA completed electronic diaries assessing clinical pain, positive affect, and negative affect. A subset of participants (n=120) underwent quantitative sensory testing, from which a single index of central sensitization to pain was derived. We used multiple regression models to test for the interactive effects of sex and affect (positive versus negative and stable versus state) on pain-related outcomes. We used mixed effects models to test for the moderating effects of sex on the relationships between state affect and pain over time. Sex differences in affect and pain were identified, with men reporting significantly higher stable positive affect and lower central sensitization to pain indexed by quantitative sensory testing, as well as marginally lower KOA-specific clinical pain compared to women. Moreover, there was an interaction between stable positive affect and sex on KOA-specific clinical pain and average daily non-specific pain ratings. Post hoc analyses revealed that men showed trends towards an inverse relationship between stable positive affect and pain outcomes, while women showed no relationship between positive affect and pain. There was also a significant interaction between sex and stable negative affect and sex on KOA-specific pain such that men showed a significantly stronger positive relationship between stable negative affect and KOA-specific pain than women. Sex did not interact with state affect on pain outcomes. Findings suggest that men may be particularly sensitive to the effects of stable positive affect and negative affect on clinical pain. Future work with larger samples is needed in order to identify potential mechanisms driving the sex-specific effects of affect on pain. The current study provides novel data that suggesting that the association of positive affect, negative affect, and pain are different in men versus women with KOA. Further understanding of the difference in affective expression between men and women may lead to the development of novel therapeutic interventions and help to identify additional modifiable factors in the prevention and management of pain. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Deficiency in endogenous modulation of prolonged heat pain in patients with Irritable Bowel Syndrome and Temporomandibular Disorder

PubMed Central

King, Christopher D.; Wong, Fong; Currie, Tom; Mauderli, Andre P.; Fillingim, Roger B.; Riley, Joseph L.

2013-01-01

Females with Irritable Bowel Syndrome (IBS) and Temporomandibular Disorder (TMD) are characterized by enhanced sensitivity to experimental pain. One possible explanation for this observation is deficiencies in pain modulation systems like Diffuse Noxious Inhibitory Control (DNIC). In a few studies that used brief stimuli, chronic pain patients demonstrate reduced DNIC. The purpose of this study was to compare sensitivity to prolonged heat pain and the efficacy of DNIC in controls to IBS and TMD patients. Heat pain (experimental stimulus; 44.0-49.0°C), which was applied to left palm, was continuously rated during three 30-second trials across three separate testing sessions under the following conditions: without a conditioning stimulus; during concurrent immersion of the right foot in a 23.0°C (control); and during noxious cold immersion in a (DNIC; 8.0-16.0°C) water bath. Compared to controls, IBS and TMD patients reported increased sensitivity to heat pain and failed to demonstrate pain inhibition due to DNIC. Controls showed a significant reduction in pain during the DNIC session. These findings support the idea that chronic pain patients are not only more pain sensitive and demonstrate reduced pain inhibition by pain, possibly because of dysfunction of endogenous pain inhibition systems. PMID:19278784

Small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia.

PubMed

Lieber, S; Blankenburg, M; Apel, K; Hirschfeld, G; Hernáiz Driever, P; Reindl, T

2018-05-01

Chemotherapy-induced Peripheral Neuropathy (CIPN) of large-fibers affects up to 20% of survivors of pediatric acute lymphoblastic leukemia (ALL). We aimed to describe small-fiber toxicity and pain sensitization in this group. In a cross-sectional, bicentric study we assessed 46 survivors of pediatric ALL (Mean age: 5.7 ± 3.5 years at diagnosis, median 2.5 years after therapy; males: 28). ≥6 years of age, ≥3 months after last administration of Vincristine, and cumulative dose of Vincristine 12 mg/m 2 . We used a reduced version of the Pediatric-modified Total Neuropathy Score (Ped-mTNS) as bedside test and Quantitative Sensory Testing (QST) for assessment of small- and large-fiber neuropathy as well as pain sensitization. We employed Nerve Conduction Studies (NCS) as the most accurate tool for detecting large-fiber neuropathy. Fifteen survivors (33%) had abnormal rPed-mTNS values (≥4 points) and 5 survivors (11%) reported pain. In QST, the survivor group showed significant (p < 0.001) inferior large-fiber function and pain sensitization when compared to healthy matched peers. We identified deficits of vibration in 33 (72%) and tactile hypoesthesia in 29 (63%), hyperalgesia to blunt pressure in 19 (41%), increased mechanical pain sensitivity in 12 (26%) and allodynia in 16 (35%) of 46 survivors. Only 7 survivors (15%) had pathologic NCS. QST is a sensitive tool that revealed signs of large-fiber neuropathy in two thirds, small-fiber neuropathy and pain sensitization in one third of survivors. Prospective studies using QST in pediatric oncology may help to elucidate the pathophysiology of small-fiber neuropathy and pain sensitization as well as their relevance for quality of survival. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Hippocampal GABAA Receptor and Pain Sensitivity during Estrous Cycle in the Rat

PubMed Central

Taherianfard, Mahnaz; Mosavi, Mahnaz

2011-01-01

Background: Estradiol and progesterone as well as hippocampal GABAA receptors are believed to play a role in the modulation of pain. The aim of present study was to investigate the effect of intrahippocampal injections of GABAA receptor agonist (muscimol) and GABAA receptor antagonist (picrotoxin) on pain sensitivity during estrous cycle. Methods: Pain sensitivity was evaluated in rats by formalin test during all stages of estrous cycle. Animals were divided into five groups including; 1- control (intact animal); 2- sham 1 receiving 0.75 µl artificial cerebrospinal fluids (ACSF); 3- sham 2 receiving 0.75 µl alcoholic ACSF; 4- experimental 1 receiving 250 or 500 µg/rat of muscimol in 0.75 µl vehicle, and 5- experimental 2 receiving 20 or 30 µg/rat picrotoxin in 0.75 µl vehicle. Data were analyzed by Kruskal-Wallis followed by Tucky's test for pairwise comparisons using a P value of ≤0.50 for statistical significance. Results: Muscimol significantly (P<0.05) decreased pain sensitivity in all stages of estrous cycle, and the analgesic effect was higher during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Picrotoxin significantly (P<0.05) increased pain sensitivity in all stages of estrous cycle, and such a hyperalgesic effect was lower during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Conclusion: The findings of the present study indicate that the role of hippocampal GABAA receptor in the control of the pain sensitivity can be modulated by variation in gonadal steroids during different stages of the estrous cycle. PMID:23115414

The time course of brief and prolonged topical 8% capsaicin-induced desensitization in healthy volunteers evaluated by quantitative sensory testing and vasomotor imaging.

PubMed

Lo Vecchio, Silvia; Andersen, Hjalte Holm; Arendt-Nielsen, Lars

2018-05-29

Topically applied high-concentration capsaicin induces reversible dermo-epidermal denervation and depletion of capsaicin-sensitive nociceptors. This causes desensitization of distinct sensory modalities and is used to treat peripheral neuropathic pain and itch. For high-concentration capsaicin, the selectivity of loss of function and functional recovery rates of various afferent fibers subpopulations are unknown. This study used comprehensive quantitative sensory testing and vasomotor imaging to assess effectiveness, duration and sensory selectivity of high-concentration 8% capsaicin-ablation. Skin areas in 14 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 1 and 24 h and underwent comprehensive sensory and vasomotor testing at 1, 7 and 21 days postpatch removal. Tests consisted of thermal detection and pain thresholds, tactile and vibration detection thresholds, mechanical pain threshold and mechanical pain sensitivity as well as micro-vascular and itch reactivity to histamine provocations. The 24 h capsaicin drastically inhibited warmth detection (P < 0.001), heat pain (P < 0.001) as well as histamine-induced itch (P < 0.05) and neurogenic flare (P < 0.001), but had no impact on tactile sensitivity, cold detection and cold pain. A marginal decrease in mechanical pain sensitivity was observed (P < 0.05). Capsaicin for 1 h had limited and transient sensory effects only affecting warmth and heat sensations. Time-dependent functional recovery was almost complete 21 days after the 24 h capsaicin exposure, while recovery of neurogenic inflammatory responsiveness remained partial. The psychophysically assessed sensory deficiencies induced by the used 8% capsaicin-ablation correspond well with a predominant effect on TRPV1 + -cutaneous fibers. The method is easy to apply, well tolerated, and utilizable for studies on, e.g., interactions between skin barrier, inflammation and capsaicin-sensitive afferents.

Effectiveness of low-level laser therapy on pain intensity, pressure pain threshold, and SF-MPQ indexes of women with myofascial pain.

PubMed

Magri, Laís Valencise; Carvalho, Vinícius Almeida; Rodrigues, Flávia Cássia Cabral; Bataglion, César; Leite-Panissi, Christie Ramos Andrade

2017-02-01

Women with temporomandibular disorders (TMD) frequently report pain areas in body regions. This process is associated with central sensitization phenomena, present in chronic pain. The low-level laser therapy (LLLT) has been reported as a therapeutic option for the painful TMD treatment. The aim of this study was to analyze the effect of LLLT on pain intensity (visual analogue scale, VAS), pain sensitivity in orofacial and corporal points (pressure pain threshold, PPT), and on Short Form-McGill Pain Questionnaire (SF-MPQ) indexes of women with myofascial pain (subtype of muscle TMD). Ninety-one women (18-60 years) were included in the study, among which 61 were diagnosed with myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorder-Ia and Ib) and were divided into laser (n = 31) and placebo group (n = 30), and 30 were controls. The LLLT was applied at pre-established points, twice a week, eight sessions (780 nm; masseter and anterior temporal = 5 J/cm 2 , 20 mW, 10 s; TMJ area = 7.5 J/cm 2 , 30 mW, 10 s). Pain intensity, pain sensitivity, and the SF-MPQ indexes were measured at the baseline, during laser sessions, and 30 days after treatment. For intra-group comparisons, the Friedman test was performed, and for inter-group, the Mann-Whitney test. Increased pain sensitivity was found in women with myofascial pain when compared to controls (p < 0.05). There was a reduction in pain intensity for both groups after LLLT. The LLLT did not change the PPT for any group (p > 0.05). Active laser and placebo reduced the indexes of sensory, total pain, and VAS, maintaining the results after 30 days; there was a reduction in the affective pain rating index for both groups, with no maintenance after 30 days for placebo, and the present pain intensity decreased in the laser group and did not change in the placebo after LLLT. In conclusion, the LLLT active or placebo are effective in reducing the overall subjective perception of myofascial pain (VAS and SF-MPQ indexes); however, they have no effectiveness in reducing the pain sensitivity in orofacial and corporal points (PPT increase).

Dairy producer attitudes to pain in cattle in relation to disbudding calves.

PubMed

Wikman, I; Hokkanen, A-H; Pastell, M; Kauppinen, T; Valros, A; Hänninen, L

2013-01-01

Pain is an important indicator of poor welfare of livestock. Despite this, pain has largely gone unrecognized in farm animals due to attitudes of producers and veterinarians, although they play a key role in monitoring and managing the perception of animal pain. Producer attitudes toward animal welfare influence livestock management and production. The aim was to quantify dairy producer attitudes to the painfulness of various cattle diseases and disbudding, a painful routine procedure performed on farm to ensure safer handling of cattle. A questionnaire on disbudding-related opinions and practices was sent to 1,000 Finnish dairy producers (response rate: 45%). Attitudes toward disbudding were gauged using a 5-point Likert scale and attitudes to cattle pain scored on an 11-point numerical rating scale. Principal components analysis was used to assess the loadings, which were further tested for differences between producer gender and housing systems with Mann-Whitney U-tests, and between herd milk yield, herd size, and age and work experience of producers with a Kruskal-Wallis test. Four main factors were identified: factor I ("taking disbudding pain seriously"), factor II ("sensitivity to pain caused by cattle diseases"), factor III ("ready to medicate calves myself"), and factor IV ("pro horns"). Female producers took disbudding pain more seriously, were more sensitive to pain caused to cattle by diseases, and were more ready to medicate disbudded calves than male producers. Producers with tie-stalls favored horns over producers with freestalls. Male producers with tie-stalls were sensitive to cattle pain and preferred horns over male producers with freestalls. Female producers with freestalls were more ready to medicate calves, but did not prefer horns more than female producers with tie-stalls. Taking disbudding seriously correlated with sensitivity to pain caused by cattle diseases. Producers with low-milk-yielding herds were less willing to medicate calves and more willing to keep cattle with horns than producers with higher-yielding herds. Older producers were more sensitive to cattle pain than middle-aged and younger producers. No effect was established for taking disbudding pain seriously: the pro-horn factor was associated with work experience, age, and herd size. Women rated pain higher and were more positive toward pain medication for animals than men. Maintaining horns are more important for producers with tie-stalls than for those with freestalls. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Clinical neurophysiology and quantitative sensory testing in the investigation of orofacial pain and sensory function.

PubMed

Jääskeläinen, Satu K

2004-01-01

Chronic orofacial pain represents a diagnostic and treatment challenge for the clinician. Some conditions, such as atypical facial pain, still lack proper diagnostic criteria, and their etiology is not known. The recent development of neurophysiological methods and quantitative sensory testing for the examination of the trigeminal somatosensory system offers several tools for diagnostic and etiological investigation of orofacial pain. This review presents some of these techniques and the results of their application in studies on orofacial pain and sensory dysfunction. Clinical neurophysiological investigation has greater diagnostic accuracy and sensitivity than clinical examination in the detection of the neurogenic abnormalities of either peripheral or central origin that may underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological testing may also reveal trigeminal pathology when magnetic resonance imaging has failed to detect it, so these methods should be considered complementary to each other in the investigation of orofacial pain patients. The blink reflex, corneal reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the recording of trigeminal somatosensory-evoked potentials with near-nerve stimulation have all proved to be sensitive and reliable in the detection of dysfunction of the myelinated sensory fibers of the trigeminal nerve or its central connections within the brainstem. With appropriately small thermodes, thermal quantitative sensory testing is useful for the detection of trigeminal small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most sensitive to lesions causing axonal injury. By combining different techniques for investigation of the trigeminal system, an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. Neurophysiological and quantitative sensory tests have already highlighted some similarities among various orofacial pain conditions and have shown heterogeneity within clinical diagnostic categories. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: results from the European Project on OSteoArthritis (EPOSA)

PubMed Central

2014-01-01

Background People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Methods Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. Results The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Conclusions Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA. PMID:24597710

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: results from the European Project on OSteoArthritis (EPOSA).

PubMed

Timmermans, Erik J; van der Pas, Suzan; Schaap, Laura A; Sánchez-Martínez, Mercedes; Zambon, Sabina; Peter, Richard; Pedersen, Nancy L; Dennison, Elaine M; Denkinger, Michael; Castell, Maria Victoria; Siviero, Paola; Herbolsheimer, Florian; Edwards, Mark H; Otero, Angel; Deeg, Dorly J H

2014-03-05

People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA.

Entropy of Masseter Muscle Pain Sensitivity: A New Technique for Pain Assessment.

PubMed

Castrillon, Eduardo E; Exposto, Fernando G; Sato, Hitoshi; Tanosoto, Tomohiro; Arima, Taro; Baad-Hansen, Lene; Svensson, Peter

2017-01-01

To test whether manipulation of mechanical pain sensitivity (MPS) of the masseter muscle is reflected in quantitative measures of entropy. In a randomized, single-blinded, placebo-controlled design, 20 healthy volunteers had glutamate, lidocaine, and isotonic saline injected into the masseter muscle. Self-assessed pain intensity on a numeric rating scale (NRS) was evaluated up to 10 minutes following the injection, and MPS was evaluated after application (at 5 minutes and 30 minutes) of three different forces (0.5 kg, 1 kg, and 2 kg) to 15 different sites of the masseter muscle. Finally, the entropy and center of gravity (COG) of the pain sensitivity scores were calculated. Analysis of variance was used to test differences in means of tested outcomes and Tukey post hoc tests were used to adjust for multiple comparisons. The main findings were: (1) Compared with both lidocaine and isotonic saline, glutamate injections caused an increase in peak, duration, and area under the NRS pain curve (P < .01); (2) A pressure of 2 kg caused the highest NRS pain scores (P < .03) and entropy values (P < .02); (3) Glutamate injections caused increases in entropy values when assessed with 0.5 kg and 1.0 kg but not with 2.0 kg of pressure; and (4) COG coordinates revealed differences between the x coordinates for time (P < .01) and time and force for the y coordinates (P < .01). These results suggest that manipulation of MPS of the masseter muscle with painful glutamate injections can increase the diversity of MPS, which is reflected in entropy measures. Entropy allows quantification of the diversity of MPS, which may be important in clinical assessment of pain states such as myofascial temporomandibular disorders.

Diagnostic Accuracy of a New High-Sensitivity Troponin I Assay and Five Accelerated Diagnostic Pathways for Ruling Out Acute Myocardial Infarction and Acute Coronary Syndrome.

PubMed

Greenslade, Jaimi H; Carlton, Edward W; Van Hise, Christopher; Cho, Elizabeth; Hawkins, Tracey; Parsonage, William A; Tate, Jillian; Ungerer, Jacobus; Cullen, Louise

2018-04-01

This diagnostic accuracy study describes the performance of 5 accelerated chest pain pathways, calculated with the new Beckman's Access high-sensitivity troponin I assay. High-sensitivity troponin I was measured with presentation and 2-hour blood samples in 1,811 patients who presented to an emergency department (ED) in Australia. Patients were classified as being at low risk according to 5 rules: modified accelerated diagnostic protocol to assess patients with chest pain symptoms using troponin as the only biomarker (m-ADAPT), the Emergency Department Assessment of Chest Pain Score (EDACS) pathway, the History, ECG, Age, Risk Factors, and Troponin (HEART) pathway, the No Objective Testing Rule, and the new Vancouver Chest Pain Rule. Endpoints were 30-day acute myocardial infarction and acute coronary syndrome. Measures of diagnostic accuracy for each rule were calculated. Data included 96 patients (5.3%) with acute myocardial infarction and 139 (7.7%) with acute coronary syndrome. The new Vancouver Chest Pain Rule and No Objective Testing Rule had high sensitivity for acute myocardial infarction (100%; 95% confidence interval [CI] 96.2% to 100% for both) and acute coronary syndrome (98.6% [95% CI 94.9% to 99.8%] and 99.3% [95% CI 96.1% to 100%]). The m-ADAPT, EDACS, and HEART pathways also yielded high sensitivity for acute myocardial infarction (96.9% [95% CI 91.1% to 99.4%] for m-ADAPT and 97.9% [95% CI 92.7% to 99.7%] for EDACS and HEART), but lower sensitivity for acute coronary syndrome (≤95.0% for all). The m-ADAPT, EDACS, and HEART rules classified more patients as being at low risk (64.3%, 62.5%, and 49.8%, respectively) than the new Vancouver Chest Pain Rule and No Objective Testing Rule (28.2% and 34.5%, respectively). In this cohort with a low prevalence of acute myocardial infarction and acute coronary syndrome, using the Beckman's Access high-sensitivity troponin I assay with the new Vancouver Chest Pain Rule or No Objective Testing Rule enabled approximately one third of patients to be safely discharged after 2-hour risk stratification with no further testing. The EDACS, m-ADAPT, or HEART pathway enabled half of ED patients to be rapidly referred for objective testing. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Pain and chewing sensitivity during fixed orthodontic treatment in extraction and non-extraction patients.

PubMed

Sayar, Gulsilay

2017-01-01

The aim of this study was to evaluate the differences in pain perception and chewing sensitivity between extraction and non-extraction patients. Thirty orthodontic patients (11 males, 19 females) were included in this study who were classified as extraction (n=15; 6 males, 9 females) and non-extraction patients (n=15; 7 males, 8 females). The mean age of patients were 15.10±1.83 years in non-extraction group and 15.44±0.75 years in extraction group. The patients were asked to complete the Visual Analogue Scale (VAS) questionnaire and they were asked to mark the presence or absence of sensitivity during 7 days after the first arch wire placement. Pain intensity comparison between groups was performed using the Mann-Whitney U test. The Friedman test was used to analyze within-group differences over time. There were no significant differences in pain scores between the groups. Pain levels significantly decreased between day 1 and day 3 in both the groups. No differences were found in the chewing sensitivity between the non-extraction and extraction groups. No difference in the pain perception was observed between the extraction and non-extraction patients during the 7 days after arch wire placement.

Sensitization of the Nociceptive System in Complex Regional Pain Syndrome

PubMed Central

Diedrichs, Carolina; Baron, Ralf; Gierthmühlen, Janne

2016-01-01

Background Complex regional pain syndrome type I (CRPS-I) is characterized by sensory, motor and autonomic abnormalities without electrophysiological evidence of a nerve lesion. Objective Aims were to investigate how sensory, autonomic and motor function change in the course of the disease. Methods 19 CRPS-I patients (17 with acute, 2 with chronic CRPS, mean duration of disease 5.7±8.3, range 1–33 months) were examined with questionnaires (LANSS, NPS, MPI, Quick DASH, multiple choice list of descriptors for sensory, motor, autonomic symptoms), motor and autonomic tests as well as quantitative sensory testing according to the German Research Network on Neuropathic Pain at two visits (baseline and 36±10.6, range 16–53 months later). Results CRPS-I patients had an improvement of sudomotor and vasomotor function, but still a great impairment of sensory and motor function upon follow-up. Although pain and mechanical detection improved upon follow-up, thermal and mechanical pain sensitivity increased, including the contralateral side. Increase in mechanical pain sensitivity and loss of mechanical detection were associated with presence of ongoing pain. Conclusions The results demonstrate that patients with CRPS-I show a sensitization of the nociceptive system in the course of the disease, for which ongoing pain seems to be the most important trigger. They further suggest that measured loss of function in CRPS-I is due to pain-induced hypoesthesia rather than a minimal nerve lesion. In conclusion, this article gives evidence for a pronociceptive pain modulation profile developing in the course of CRPS and thus helps to assess underlying mechanisms of CRPS that contribute to the maintenance of patients’ pain and disability. PMID:27149519

Relationship between cold pressor pain-sensitivity and sleep quality in opioid-dependent males on methadone treatment

PubMed Central

Lee, Chee Siong; Tan, Soo Choon; Mohamad, Nasir; Lee, Yeong Yeh; Ismail, Rusli

2015-01-01

Aim. Poor sleep quality due to pain has been reported among opioid-dependent male patients on methadone maintenance therapy (MMT) but objective pain data are lacking. This study aimed to investigate the rate of pain-sensitivity using cold pressor test (CPT) and the relationship between pain-sensitivity and sleep quality in this population. Methods. A total of 168 male participants were included into the study. Objective pain-tolerance was evaluated at 0 h and at 24 h after the first CPT. Malay version of the Pittsburgh Sleep Quality Index (PSQI) and the subjective opiate withdrawal scale (SOWS) questionnaires were administered to evaluate the quality of sleep and withdrawal symptoms, respectively. Results. The mean age of study participants was 37.22 (SD 6.20) years old. Mean daily methadone dose was 76.64 (SD 37.63) mg/day, mean global PSQI score was 5.47 (SD 2.74) and mean averaged SOWS score was 5.43 (SD 6.91). The averaged pain-tolerance time ranged from 7 to 300 s with a mean time of 32.16 (SE 2.72) s, slightly below the cut-off score of 37.53 s. More specifically, 78.6% (n = 132) of participants were identified as pain-sensitive (averaged pain-tolerance time ≤37.53 s), and 36 (21.4%) participants were pain-tolerant (averaged pain-tolerance time >37.53 s). The pain-sensitive group reported poorer sleep quality with mean (SD) PSQI of 5.78 (2.80) compared with the pain-tolerant group with mean (SD) PSQI of 4.31 (2.18) (p = 0.005). With analysis of covariance, pain-sensitive group was found to have higher global PSQI scores (adjusted mean 5.76, 95% CI 5.29; 6.22) than pain-tolerant participants (adjusted mean 4.42, 95% CI 3.52; 5.32) (p = 0.010). Conclusions. Majority of opioid-dependent male patients on methadone treatment are pain-sensitive with CPT. Poor sleep quality is associated with cold pressor pain-sensitivity. Pain and sleep complaints in this male population should not be overlooked. PMID:25870765

Incidence of foot rotation, pelvic crest unleveling, and supine leg length alignment asymmetry and their relationship to self-reported back pain.

PubMed

Knutson, Gary A

2002-02-01

To determine the incidence of pelvic unleveling, foot rotation, and supine leg length alignment asymmetry in a nonclinical population and to examine the validity (sensitivity, specificity, positive and negative predictive values) of these visual tests and their relationship to self-reported back pain. Volunteers answered a questionnaire regarding back pain and were then examined by a chiropractor who was unaware of the status of their back pain. Seventy-four unscreened volunteers answered the questionnaire. The association of visual tests with back pain and their validity indices; Visual Analogue Scale ratings. Fifty-one percent (n = 74) of volunteers examined had supine leg length alignment asymmetry (LLA). Pain intensity on a Visual Analogue Scale was significantly higher (P <.001) for those demonstrating supine LLA than for those without LLA. Those with back pain and recurrent back pain were significantly (P <.001) more likely to have supine LLA. The validity indices of the supine leg check showed acceptable levels for sensitivity (74%), specificity (78%), and positive predictive value (82%) [corrected] in recurrent back pain. Findings also indicated a high incidence of supine LLA in volunteers with chronic back pain (85%). The results indicated that, in this group of volunteers, the supine leg length alignment check had clinical validity as a stand-alone test for recurring back pain. Further testing on a larger, statistically defined cross-section of the population is recommended.

Diagnostic Accuracy of the Slump Test for Identifying Neuropathic Pain in the Lower Limb.

PubMed

Urban, Lawrence M; MacNeil, Brian J

2015-08-01

Diagnostic accuracy study with nonconsecutive enrollment. To assess the diagnostic accuracy of the slump test for neuropathic pain (NeP) in those with low to moderate levels of chronic low back pain (LBP), and to determine whether accuracy of the slump test improves by adding anatomical or qualitative pain descriptors. Neuropathic pain has been linked with poor outcomes, likely due to inadequate diagnosis, which precludes treatment specific for NeP. Current diagnostic approaches are time consuming or lack accuracy. A convenience sample of 21 individuals with LBP, with or without radiating leg pain, was recruited. A standardized neurosensory examination was used to determine the reference diagnosis for NeP. Afterward, the slump test was administered to all participants. Reports of pain location and quality produced during the slump test were recorded. The neurosensory examination designated 11 of the 21 participants with LBP/sciatica as having NeP. The slump test displayed high sensitivity (0.91), moderate specificity (0.70), a positive likelihood ratio of 3.03, and a negative likelihood ratio of 0.13. Adding the criterion of pain below the knee significantly increased specificity to 1.00 (positive likelihood ratio = 11.9). Pain-quality descriptors did not improve diagnostic accuracy. The slump test was highly sensitive in identifying NeP within the study sample. Adding a pain-location criterion improved specificity. Combining the diagnostic outcomes was very effective in identifying all those without NeP and half of those with NeP. Limitations arising from the small and narrow spectrum of participants with LBP/sciatica sampled within the study prevent application of the findings to a wider population. Diagnosis, level 4-.

Effect of mental stress on cold pain in chronic tension-type headache sufferers.

PubMed

Cathcart, Stuart; Winefield, Anthony H; Lushington, Kurt; Rolan, Paul

2009-10-01

Mental stress is a noted contributing factor in chronic tension-type headache (CTH), however the mechanisms underlying this are not clearly understood. One proposition is that stress aggravates already increased pain sensitivity in CTH sufferers. This hypothesis could be partially tested by examining effects of mental stress on threshold and supra-threshold experimental pain processing in CTH sufferers. Such studies have not been reported to date. The present study measured pain detection and tolerance thresholds and ratings of supra-threshold pain stimulation from cold pressor test in CTH sufferers (CTH-S) and healthy Control (CNT) subjects exposed to a 60-min stressful mental task, and in CTH sufferers exposed to a 60-min neutral condition (CTH-N). Headache sufferers had lower pain tolerance thresholds and increased pain intensity ratings compared to controls. Pain detection and tolerance thresholds decreased and pain intensity ratings increased during the stress task, with a greater reduction in pain detection threshold and increase in pain intensity ratings in the CTH-S compared to CNT group. The results support the hypothesis that mental stress contributes to CTH through aggravating already increased pain sensitivity in CTH sufferers.

Comparison of cranio-cervical flexion training versus cervical proprioception training in patients with chronic neck pain: A randomized controlled clinical trial.

PubMed

Gallego Izquierdo, Tomás; Pecos-Martin, Daniel; Lluch Girbés, Enrique; Plaza-Manzano, Gustavo; Rodríguez Caldentey, Ricardo; Mayor Melús, Rodrigo; Blanco Mariscal, Diego; Falla, Deborah

2016-01-01

To compare the effects of cranio-cervical flexion vs cervical proprioception training on neuromuscular control, pressure pain sensitivity and perceived pain and disability in patients with chronic neck pain. Twenty-eight volunteers with chronic non-specific neck pain were randomly assigned to 1 of 2 interventions and undertook 6 physiotherapist-supervised sessions over a period of 2 months. Both groups performed daily home exercise. Performance on the cranio-cervical flexion test, pressure pain thresholds and reported levels of pain and disability were measured before and immediately after the first treatment session, 1 month after starting treatment and 2 months after starting treatment (at completion of the intervention). At 2 months, both groups improved their performance on the cranio-cervical flexion test (p < 0.05), but this did not differ between groups (p > 0.05). Both groups showed a reduction in their pain at rest and disability at 2 months, but this was also not different between groups (p > 0.05). Pressure pain sensitivity did not change for either group. Both specific cranio-cervical flexion training and proprioception training had a comparable effect on performance on the cranio-cervical flexion test, a test of the neuromuscular control of the deep cervical flexors. These results indicate that proprioception training may have positive effects on the function of the deep cervical flexors.

Chronic Widespread Back Pain is Distinct From Chronic Local Back Pain: Evidence From Quantitative Sensory Testing, Pain Drawings, and Psychometrics.

PubMed

Gerhardt, Andreas; Eich, Wolfgang; Janke, Susanne; Leisner, Sabine; Treede, Rolf-Detlef; Tesarz, Jonas

2016-07-01

Whether chronic localized pain (CLP) and chronic widespread pain (CWP) have different mechanisms or to what extent they overlap in their pathophysiology is controversial. The study compared quantitative sensory testing profiles of nonspecific chronic back pain patients with CLP (n=48) and CWP (n=29) with and fibromyalgia syndrome (FMS) patients (n=90) and pain-free controls (n = 40). The quantitative sensory testing protocol of the "German-Research-Network-on-Neuropathic-Pain" was used to measure evoked pain on the painful area in the lower back and the pain-free hand (thermal and mechanical detection and pain thresholds, vibration threshold, pain sensitivity to sharp and blunt mechanical stimuli). Ongoing pain and psychometrics were captured with pain drawings and questionnaires. CLP patients did not differ from pain-free controls, except for lower pressure pain threshold (PPT) on the back. CWP and FMS patients showed lower heat pain threshold and higher wind-up ratio on the back and lower heat pain threshold and cold pain threshold on the hand. FMS showed lower PPT on back and hand, and higher comorbidity of anxiety and depression and more functional impairment than all other groups. Even after long duration CLP presents with a local hypersensitivity for PPT, suggesting a somatotopically specific sensitization of nociceptive processing. However, CWP patients show widespread ongoing pain and hyperalgesia for different stimuli that is generalized in space, suggesting the involvement of descending control systems, as also suggested for FMS patients. Because mechanisms in nonspecific chronic back pain with CLP and CWP differ, these patients should be distinguished in future research and allocated to different treatments.

Masticatory and cervical muscle tenderness and pain sensitivity in a remote area in subjects with a temporomandibular disorder and neck disability.

PubMed

Silveira, Anelise; Armijo-Olivo, Susan; Gadotti, Inae C; Magee, David

2014-01-01

To compare the masticatory and cervical muscle tenderness and pain sensitivity in the hand (remote region) between patients with temporomandibular disorders (TMD) and healthy controls. Twenty female subjects were diagnosed with chronic TMD, and 20 were considered healthy. Subjects completed the Neck Disability Index and Limitations of Daily Functions in a TMD questionnaire. Tenderness of the masticatory and cervical muscles and pain sensitivity in the hand were measured using an algometer. Three-way mixed analysis of variance (ANOVA) evaluated differences in muscle tenderness between groups. One-way ANOVA compared pain sensitivity in the hand between groups. Effect sizes were assessed using Cohen guidelines. Significantly increased masticatory and cervical muscle tenderness and pain sensitivity in the hand were found in subjects with TMD when compared with healthy subjects. Moderate to high effect sizes showed the clinical relevance of the findings. The results of this study have highlighted the importance of assessing TMD patients not only in the craniofacial region but also in the neck and other parts of the body. Future studies should focus on testing the effectiveness of treatments addressing the neck and the pain sensitivity in the hand in patients with TMD.

Predicting Persistent Back Symptoms by Psychosocial Risk Factors: Validity Criteria for the ÖMPSQ and the HKF-R 10 in Germany.

PubMed

Riewe, E; Neubauer, E; Pfeifer, A C; Schiltenwolf, M

2016-01-01

10% of all individuals in Germany develop persistent symptoms due to nonspecific back pain (NSBP) causing up to 90% of direct and indirect expenses for health care systems. Evidence indicates a strong relationship between chronic nonspecific back pain and psychosocial risk factors. The Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) and the German Heidelberger Kurzfragebogen Rückenschmerz (HKF-R 10) are deemed valid in prediction of persistent pain, functional loss or amount of sick leave. This study provides and discusses validity criteria for these questionnaires using ROC-curve analyses. Quality measurements included sensitivity and specificity, likelihood-ratio related test-efficiencies and clinical utility in regard to predictive values. 265 patients recruited from primary and secondary care units completed both questionnaires during the same timeframe. From the total, 133 patients returned a 6-month follow-up questionnaire to assess the validity criteria for outcomes of pain, function and sick leave. Based on heterogeneous cut-offs for the ÖMPSQ, sensitivity and specificity were moderate for outcome of pain (72%/75%). Very high sensitivity was observed for function (97%/57%) and high specificity for sick leave (63%/85%). The latter also applied to the HKF-R 10 (pain 50%/84%). Proportions between sensitivity and specificity were unbalanced except for the ÖMPSQ outcome of pain. Likelihood-ratios and positive predictive values ranged from low to moderate. Although the ÖMPSQ may be considered useful in identification of long-term functional loss or pain, over- and underestimation of patients at risk of chronic noncspecific back pain led to limited test-efficiencies and clinical utility for both questionnaires. Further studies are required to quantify the predictive validity of both questionnaires in Germany.

Pressure and cold pain threshold reference values in a large, young adult, pain-free population.

PubMed

Waller, Robert; Smith, Anne Julia; O'Sullivan, Peter Bruce; Slater, Helen; Sterling, Michele; McVeigh, Joanne Alexandra; Straker, Leon Melville

2016-10-01

Currently there is a lack of large population studies that have investigated pain sensitivity distributions in healthy pain free people. The aims of this study were: (1) to provide sex-specific reference values of pressure and cold pain thresholds in young pain-free adults; (2) to examine the association of potential correlates of pain sensitivity with pain threshold values. This study investigated sex specific pressure and cold pain threshold estimates for young pain free adults aged 21-24 years. A cross-sectional design was utilised using participants (n=617) from the Western Australian Pregnancy Cohort (Raine) Study at the 22-year follow-up. The association of site, sex, height, weight, smoking, health related quality of life, psychological measures and activity with pain threshold values was examined. Pressure pain threshold (lumbar spine, tibialis anterior, neck and dorsal wrist) and cold pain threshold (dorsal wrist) were assessed using standardised quantitative sensory testing protocols. Reference values for pressure pain threshold (four body sites) stratified by sex and site, and cold pain threshold (dorsal wrist) stratified by sex are provided. Statistically significant, independent correlates of increased pressure pain sensitivity measures were site (neck, dorsal wrist), sex (female), higher waist-hip ratio and poorer mental health. Statistically significant, independent correlates of increased cold pain sensitivity measures were, sex (female), poorer mental health and smoking. These data provide the most comprehensive and robust sex specific reference values for pressure pain threshold specific to four body sites and cold pain threshold at the dorsal wrist for young adults aged 21-24 years. Establishing normative values in this young age group is important given that the transition from adolescence to adulthood is a critical temporal period during which trajectories for persistent pain can be established. These data will provide an important research resource to enable more accurate profiling and interpretation of pain sensitivity in clinical pain disorders in young adults. The robust and comprehensive data can assist interpretation of future clinical pain studies and provide further insight into the complex associations of pain sensitivity that can be used in future research. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Co-occurrence of Pain Symptoms and Somatosensory Sensitivity in Burning Mouth Syndrome: A Systematic Review

PubMed Central

Moisset, Xavier; Calbacho, Valentina; Torres, Pilar; Gremeau-Richard, Christelle; Dallel, Radhouane

2016-01-01

Background Burning mouth syndrome (BMS) is a chronic and spontaneous oral pain with burning quality in the tongue or other oral mucosa without any identifiable oral lesion or laboratory finding. Pathogenesis and etiology of BMS are still unknown. However, BMS has been associated with other chronic pain syndromes including other idiopathic orofacial pain, the dynias group and the family of central sensitivity syndromes. This would imply that BMS shares common mechanisms with other cephalic and/or extracephalic chronic pains. The primary aim of this systematic review was to determine whether BMS is actually associated with other pain syndromes, and to analyze cephalic and extracephalic somatosensory sensitivity in these patients. Methods This report followed the PRISMA Statement. An electronic search was performed until January 2015 in PubMed, Cochrane library, Wiley and ScienceDirect. Searched terms included “burning mouth syndrome OR stomatodynia OR glossodynia OR burning tongue OR oral burning”. Studies were selected according to predefined inclusion criteria (report of an association between BMS and other pain(s) symptoms or of cutaneous cephalic and/or extracephalic quantitative sensory testing in BMS patients), and a descriptive analysis conducted. Results The search retrieved 1512 reports. Out of these, twelve articles met criteria for co-occurring pain symptoms and nine studies for quantitative sensory testing (QST) in BMS patients. The analysis reveals that in BMS patients co-occurring pain symptoms are rare, assessed by only 0.8% (12 of 1512) of the retrieved studies. BMS was associated with headaches, TMD, atypical facial pain, trigeminal neuralgia, post-herpetic facial pain, back pain, fibromyalgia, joint pain, abdominal pain, rectal pain or vulvodynia. However, the prevalence of pain symptoms in BMS patients is not different from that in the age-matched general population. QST studies reveal no or inconsistent evidence of abnormal cutaneous cephalic and extracephalic somatosensory sensitivity. Conclusions There is no evidence for a high rate of other pain symptoms or somatosensory impairments co-occurring with BMS. These results thus suggest that BMS rather depends on specific mechanisms, likely at the trigeminal level. Nevertheless, more thoroughly conducted research is required to draw definitive conclusion. PMID:27657531

Evoked Temporal Summation in Cats to Highlight Central Sensitization Related to Osteoarthritis-Associated Chronic Pain: A Preliminary Study

PubMed Central

Guillot, Martin; Taylor, Polly M.; Rialland, Pascale; Klinck, Mary P.; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Troncy, Eric

2014-01-01

In cats, osteoarthritis causes significant chronic pain. Chronicity of pain is associated with changes in the central nervous system related to central sensitization, which have to be quantified. Our objectives were 1) to develop a quantitative sensory testing device in cats for applying repetitive mechanical stimuli that would evoke temporal summation; 2) to determine the sensitivity of this test to osteoarthritis-associated pain, and 3) to examine the possible correlation between the quantitative sensory testing and assessment using other pain evaluation methods. We hypothesized that mechanical sub-threshold repetitive stimuli would evoke temporal summation, and that cats with osteoarthritis would show a faster response. A blinded longitudinal study was performed in 4 non-osteoarthritis cats and 10 cats with naturally occurring osteoarthritis. Quantification of chronic osteoarthritis pain-related disability was performed over a two week period using peak vertical force kinetic measurement, motor activity intensity assessment and von Frey anesthesiometer-induced paw withdrawal threshold testing. The cats afflicted with osteoarthritis demonstrated characteristic findings consistent with osteoarthritis-associated chronic pain. After a 14-day acclimation period, repetitive mechanical sub-threshold stimuli were applied using a purpose-developed device. Four stimulation profiles of predetermined intensity, duration and time interval were applied randomly four times during a four-day period. The stimulation profiles were different (P<0.001): the higher the intensity of the stimulus, the sooner it produced a consistent painful response. The cats afflicted with osteoarthritis responded more rapidly than cats osteoarthritis free (P = 0.019). There was a positive correlation between the von Frey anesthesiometer-induced paw withdrawal threshold and the response to stimulation profiles #2 (2N/0.4 Hz) and #4 (2N/0.4 Hz): Rhos = 0.64 (P = 0.01) and 0.63 (P = 0.02) respectively. This study is the first report of mechanical temporal summation in awake cats. Our results suggest that central sensitization develops in cats with naturally occurring osteoarthritis, providing an opportunity to improve translational research in osteoarthritis-associated chronic pain. PMID:24859251

Depression and Pain in Asian and White Americans With Knee Osteoarthritis.

PubMed

Ahn, Hyochol; Weaver, Michael; Lyon, Debra; Choi, Eunyoung; Fillingim, Roger B

2017-10-01

Few studies have examined the underlying psychosocial mechanisms of pain in Asian Americans. Using the biopsychosocial model, we sought to determine whether variations in depression contribute to racial group differences in symptomatic knee osteoarthritis pain between Asian Americans and non-Hispanic white Americans. The sample consisted of 100 participants, including 50 Asian Americans (28 Korean Americans, 9 Chinese Americans, 7 Japanese Americans, 5 Filipino Americans, and 1 Indian American) and 50 age- and sex-matched non-Hispanic white Americans with symptomatic knee osteoarthritis pain. The Centers for Epidemiologic Studies Depression Scale was used to assess symptoms of depression, and the Western Ontario and McMaster Universities Osteoarthritis Index and the Graded Chronic Pain Scale were used to measure clinical pain. In addition, quantitative sensory testing was used to measure experimental sensitivity to heat- and mechanically-induced pain. The results indicated that higher levels of depression in Asian Americans may contribute to greater clinical pain and experimental pain sensitivity. These findings add to the growing literature regarding ethnic and racial differences in pain and its associated psychological conditions, and additional research is warranted to strengthen these findings. This article shows the contribution of depression to clinical pain and experimental pain sensitivity in Asian Americans with knee osteoarthritis. Our results suggest that Asian Americans have higher levels of depressive symptoms and that depression plays a relevant role in greater clinical pain and experimental pain sensitivity in Asian Americans. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

A SCN10A SNP biases human pain sensitivity

PubMed Central

Duan, Guangyou; Han, Chongyang; Wang, Qingli; Guo, Shanna; Zhang, Yuhao; Ying, Ying; Huang, Penghao; Zhang, Li; Macala, Lawrence; Shah, Palak; Zhang, Mi; Li, Ningbo; Dib-Hajj, Sulayman D; Zhang, Xianwei

2016-01-01

Background: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined. Results: Candidate single nucleotide polymorphism association approach together with experimental pain testing in human subjects was used to explore possible common SCN10A missense variants that might affect human pain sensitivity. We demonstrated an association between rs6795970 (G > A; p.Ala1073Val) and higher thresholds for mechanical pain in a discovery cohort (496 subjects) and confirmed it in a larger replication cohort (1005 female subjects). Functional assessments showed that although the minor allele shifts channel activation by −4.3 mV, a proexcitatory attribute, it accelerates inactivation, an antiexcitatory attribute, with the net effect being reduced repetitive firing of dorsal root ganglion neurons, consistent with lower mechanical pain sensitivity. Conclusions: At the association and mechanistic levels, the SCN10A single nucleotide polymorphism rs6795970 biases human pain sensitivity. PMID:27590072

Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

PubMed

Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

2016-10-01

The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations.

Inflammation-induced pain sensitization in men and women: does sex matter in experimental endotoxemia?

PubMed Central

Wegner, Alexander; Elsenbruch, Sigrid; Rebernik, Laura; Roderigo, Till; Engelbrecht, Elisa; Jäger, Marcus; Engler, Harald; Schedlowski, Manfred; Benson, Sven

2015-01-01

Abstract A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-α and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes. PMID:26058036

Multiple Levels of Suffering: Discrimination in Health-Care Settings is Associated With Enhanced Laboratory Pain Sensitivity in Sickle Cell Disease.

PubMed

Mathur, Vani A; Kiley, Kasey B; Haywood, Carlton; Bediako, Shawn M; Lanzkron, Sophie; Carroll, C Patrick; Buenaver, Luis F; Pejsa, Megan; Edwards, Robert R; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-12-01

People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology.

Somatosensory nociceptive characteristics differentiate subgroups in people with chronic low back pain: a cluster analysis.

PubMed

Rabey, Martin; Slater, Helen; OʼSullivan, Peter; Beales, Darren; Smith, Anne

2015-10-01

The objectives of this study were to explore the existence of subgroups in a cohort with chronic low back pain (n = 294) based on the results of multimodal sensory testing and profile subgroups on demographic, psychological, lifestyle, and general health factors. Bedside (2-point discrimination, brush, vibration and pinprick perception, temporal summation on repeated monofilament stimulation) and laboratory (mechanical detection threshold, pressure, heat and cold pain thresholds, conditioned pain modulation) sensory testing were examined at wrist and lumbar sites. Data were entered into principal component analysis, and 5 component scores were entered into latent class analysis. Three clusters, with different sensory characteristics, were derived. Cluster 1 (31.9%) was characterised by average to high temperature and pressure pain sensitivity. Cluster 2 (52.0%) was characterised by average to high pressure pain sensitivity. Cluster 3 (16.0%) was characterised by low temperature and pressure pain sensitivity. Temporal summation occurred significantly more frequently in cluster 1. Subgroups were profiled on pain intensity, disability, depression, anxiety, stress, life events, fear avoidance, catastrophizing, perception of the low back region, comorbidities, body mass index, multiple pain sites, sleep, and activity levels. Clusters 1 and 2 had a significantly greater proportion of female participants and higher depression and sleep disturbance scores than cluster 3. The proportion of participants undertaking <300 minutes per week of moderate activity was significantly greater in cluster 1 than in clusters 2 and 3. Low back pain, therefore, does not appear to be homogeneous. Pain mechanisms relating to presentations of each subgroup were postulated. Future research may investigate prognoses and interventions tailored towards these subgroups.

Adaptability to pain is associated with potency of local pain inhibition, but not conditioned pain modulation: a healthy human study.

PubMed

Zheng, Zhen; Wang, Kelun; Yao, Dongyuan; Xue, Charlie C L; Arendt-Nielsen, Lars

2014-05-01

This study investigated the relationship between pain sensitivity, adaptability, and potency of endogenous pain inhibition, including conditioned pain modulation (CPM) and local pain inhibition. Forty-one healthy volunteers (20 male, 21 female) received conditioning stimulation (CS) over 2 sessions in a random order: tonic heat pain (46 °C) on the right leg for 7 minutes and cold pressor pain (1 °C to 4 °C) on the left hand for 5 minutes. Participants rated the intensity of pain continuously using a 0 to 10 electronic visual analogue scale. The primary outcome measures were pressure pain thresholds (PPT) measured at the heterotopic and homotopic location to the CS sites before, during, and 20 minutes after CS. Two groups of participants, pain adaptive and pain nonadaptive, were identified based on their response to pain in the cold pressor test. Pain-adaptive participants showed a pain reduction between peak pain and pain at end of the test by at least 2 of 10 (n=16); whereas the pain-nonadaptive participants reported unchanged peak pain during 5-minute CS (n=25). Heterotopic PPTs during the CS did not differ between the 2 groups. However, increased homotopic PPTs measured 20 minutes after CS correlated with the amount of pain reduction during CS. These results suggest that individual sensitivity and adaptability to pain does not correlate with the potency of CPM. Adaptability to pain is associated with longer-lasting local pain inhibition. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Potential neurobiological benefits of exercise in chronic pain and posttraumatic stress disorder: Pilot study.

PubMed

Scioli-Salter, Erica; Forman, Daniel E; Otis, John D; Tun, Carlos; Allsup, Kelly; Marx, Christine E; Hauger, Richard L; Shipherd, Jillian C; Higgins, Diana; Tyzik, Anna; Rasmusson, Ann M

2016-01-01

This pilot study assessed the effects of cardiopulmonary exercise testing and cardiorespiratory fitness on plasma neuropeptide Y (NPY), allopregnanolone and pregnanolone (ALLO), cortisol, and dehydroepiandrosterone (DHEA), and their association with pain sensitivity. Medication-free trauma-exposed participants were either healthy (n = 7) or experiencing comorbid chronic pain/posttraumatic stress disorder (PTSD) (n = 5). Peak oxygen consumption (VO2) during exercise testing was used to characterize cardiorespiratory fitness. Peak VO2 correlated with baseline and peak NPY levels (r = 0.66, p < 0.05 and r = 0.69, p < 0.05, respectively), as well as exercise-induced changes in ALLO (r = 0.89, p < 0.001) and peak ALLO levels (r = 0.71, p < 0.01). NPY levels at the peak of exercise correlated with pain threshold 30 min after exercise (r = 0.65, p < 0.05), while exercise-induced increases in ALLO correlated with pain tolerance 30 min after exercise (r = 0.64, p < 0.05). In contrast, exercise-induced changes in cortisol and DHEA levels were inversely correlated with pain tolerance after exercise (r = -0.69, p < 0.05 and r = -0.58, p < 0.05, respectively). These data suggest that cardiorespiratory fitness is associated with higher plasma NPY levels and increased ALLO responses to exercise, which in turn relate to pain sensitivity. Future work will examine whether progressive exercise training increases cardiorespiratory fitness in association with increases in NPY and ALLO and reductions in pain sensitivity in chronic pain patients with PTSD.

Performance of the Angle Labor Pain Questionnaire During Initiation of Epidural Analgesia in Early Active Labor.

PubMed

Angle, Pamela J; Kurtz Landy, Christine; Djordjevic, Jasmine; Barrett, Jon; Kibbe, Alanna; Sriparamananthan, Saiena; Lee, Yuna; Hamata, Lydia; Zaki, Pearl; Kiss, Alex

2016-12-01

The Angle Labor Pain Questionnaire (A-LPQ) is a new, 22-item multidimensional psychometric questionnaire that measures the 5 most important dimensions of women's childbirth pain experiences using 5 subscales: The Enormity of the Pain, Fear/Anxiety, Uterine Contraction Pain, Birthing Pain, and Back Pain/Long Haul. Previous work showed that the A-LPQ has overall good psychometric properties and performance during early active labor in women without pain relief. The current study assessed the tool's sensitivity to change during initiation of labor epidural analgesia with the standardized response mean (SRM, primary outcome). Two versions of the A-LPQ were administered once, in each of 2 test sessions, by the same trained interviewer during early active labor. The sequence of administration was randomized (ie, standard question order version [Test 1] followed by mixed version [Test 2] or vice versa). Test 1 was completed before epidural insertion; Test 2 commenced 20 to 30 minutes after the test dose. Providers assessed/treated pain independently of the study. Sensitivity to change was assessed using SRMs, Cohen's d, and paired t tests. Overall pain intensity was concurrently examined using Numeric Rating Scale and the Verbal Rating Scale (VRS); coping was assessed with the Pain Mastery Scale. Changes in pain were measured with the Patient Global Impression of Change Scale. Internal consistency was assessed with Cronbach's α. Concurrent validity with other tools was assessed using Spearman's rank correlation coefficient. A total of 51 complete datasets were analyzed. Most women reported moderate (63%, 32/51) or severe (18%, 9/51) baseline pain on VRS scores during Test 1; 29% (15/51) reported mild pain, and 6% (3/51) reported moderate pain during Test 2. Approximately 90% (46/51) of women reported much or very much improved pain at the end of testing. Cronbach's α for A-LPQ summary scores was excellent (0.94) and ranged from 0.78 (acceptable) to 0.92 (excellent) for subscales (Test 1). Large SRMs were found for A-LPQ summary scores (1.6, 95% CI: 1.2, 2.1) and all subscales except the Birthing Pain subscale (moderate, 0.60, 95% CI: 0.23, 0.97). Significant (P < .001) differences were found between A-LPQ summary scores and between all subscales on paired t tests. Correlations between A-LPQ summary and Numeric Rating Scale scores (overall pain intensity) were strong (ρ > 0.73), correlations were moderate (ρ > 0.5) with VRS scores and coping scores (ρ > 0.67). Findings support A-LPQ use for measurement of women's childbirth pain experiences during initiation of labor epidural analgesia during early active labor. Combined with our previous work, they also support the use of the A-LPQ in late labor and at delivery.

Relationships between psychological state, abuse, somatization and visceral pain sensitivity in irritable bowel syndrome

PubMed Central

Grinsvall, Cecilia; Törnblom, Hans; Tack, Jan; Van Oudenhove, Lukas; Simrén, Magnus

2018-01-01

Background and objective Psychological states may interfere with visceral sensitivity. Here we investigate associations between psychosocial factors and visceral sensitivity in irritable bowel syndrome (IBS). Methods Two IBS patient cohorts (Cohort 1: n = 231, Rome II; Cohort 2: n = 141, Rome III) underwent rectal barostat testing, and completed questionnaires for anxiety, depression, somatization, and abuse. The associations between questionnaire measures and visceral sensitivity parameters were analyzed in three-step general linear models (step1: demographic and abuse variables; step 2: anxiety and depression; step 3: somatization). Results Cohort 1. Pain threshold was positively associated with age and female gender, and negatively with adult sexual abuse and somatization. Pain referral area was negatively associated with age and positively with somatization and GI-specific anxiety, the latter effect mediated by somatization. Cohort 2. Pain threshold was positively associated with age and male gender, and negatively with adult sexual abuse. Pain intensity ratings were positively associated with somatization, female gender and depression, the latter effect mediated by somatization. Conclusion Somatization is associated with most visceral sensitivity parameters, and mediates the effect of some psychological factors on visceral sensitivity. It may reflect a psychobiological sensitization process driving symptom generation in IBS. In addition, abuse history was found to independently affect some visceral sensitivity parameters. PMID:29511560

[Prediction of postoperative pain on the basis of the psychological characteristics of patients and standard pain stimuli].

PubMed

Stepanova, Ia V; Shchelkova, O Iu; Lebedinskiĭ, K M; Mazurok, V A

2013-01-01

Practical physicians do not have instruments for objective pain assessment despite recent advances of neurophysiology and pain pharmacology. The article deals with the study of relations between preoperative pain sensitivity (finger prick and venipuncture) and pain level after surgery. 60 patients involved in the study were divided into two groups. Pain sensitivity was assessed in all patients by visual analogue scale before surgery, after awaking, in 1 hour and in 3 hours after awaking and in 1 day after the surgery. Psychological status of patients was assessed by integration anxious test, neurotic disorders questionnaire and type of attitude to the disease questionnaire. All patients were assessed by 70 criteria (54 psychological). Results of the study show that postoperative pain syndrome is affected by different psychophysiological factors. Therefore it is difficult to forecast the level of postoperative pain syndrome.

The "moving valgus stress test" for medial collateral ligament tears of the elbow.

PubMed

O'Driscoll, Shawn W M; Lawton, Richard L; Smith, Adam M

2005-02-01

The diagnosis of a painful partial tear of the medial collateral ligament in overhead-throwing athletes is challenging, even for experienced elbow surgeons and despite the use of sophisticated imaging techniques. The "moving valgus stress test" is an accurate physical examination technique for diagnosis of medial collateral ligament attenuation in the elbow. Cohort study (diagnosis); Level of evidence, 2. Twenty-one patients underwent surgical intervention for medial elbow pain due to medial collateral ligament insufficiency or other abnormality of chronic valgus overload, and they were assessed preoperatively with an examination called the moving valgus stress test. To perform the moving valgus stress test, the examiner applies and maintains a constant moderate valgus torque to the fully flexed elbow and then quickly extends the elbow. The test is positive if the medial elbow pain is reproduced at the medial collateral ligament and is at maximum between 120 degrees and 70 degrees. The moving valgus stress test was highly sensitive (100%, 17 of 17 patients) and specific (75%, 3 of 4 patients) when compared to assessment of the medial collateral ligament by surgical exploration or arthroscopic valgus stress testing. The mean shear range (ie, the arc within which pain was produced with the moving valgus stress test) was 120 degrees to 70 degrees. The mean angle at which pain was at a maximum was 90 degrees of elbow flexion. The moving valgus stress test is an accurate physical examination technique that, when performed and interpreted correctly, is highly sensitive for medial elbow pain arising from the medial collateral ligament.

Vitamin D, Race, and Experimental Pain Sensitivity in Older Adults with Knee Osteoarthritis

PubMed Central

Glover, T.L.; Goodin, B.R.; Horgas, A.L.; Kindler, L.L.; King, C.D.; Sibille, K.T.; Peloquin, C.A.; Riley, J.L.; Staud, R.; Bradley, L.A.; Fillingim, R.B.

2012-01-01

Objective Low levels of serum circulating 25-hydroxyvitamin D have been correlated with many health conditions, including chronic pain. Recent clinical practice guidelines define vitamin D levels < 20 ng/mL as deficient and values of 21–29 ng/mL as insufficient. Vitamin D insufficiency, including the most severe levels of deficiency, is more prevalent in black Americans. Ethnic and race group differences have been reported in both clinical and experimental pain, with black Americans reporting increased pain. The purpose of this study was to examine whether variation in vitamin D levels contribute to race differences in knee osteoarthritic pain. Methods The sample consisted of 94 participants (75% female), including 45 blacks and 49 whites with symptomatic knee osteoarthritis. Average age was 55.8 years (range 45–71 years). Participants completed a questionnaire on knee osteoarthritic symptoms and underwent quantitative sensory testing, including measures of heat and mechanical pain sensitivity. Results Blacks had significantly lower levels of vitamin D compared to whites, demonstrated greater clinical pain, and showed greater sensitivity to mechanical and heat pain. Low levels of vitamin D predicted increased experimental pain sensitivity, but did not predict self-reported clinical pain. Group differences in vitamin D significantly predicted group differences in heat pain and pressure pain thresholds on the index knee and ipsilateral forearm. Conclusion These data demonstrate race differences in experimental pain are mediated by differences in vitamin D level. Vitamin D deficiency may be a risk factor for increased knee osteoarthritic pain in black Americans. PMID:23135697

Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin

PubMed Central

Hogan, Dale; Baker, Alyssa L.; Morón, Jose A.; Carlton, Susan M.

2013-01-01

Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity – either hyperalgesia and/or allodynia. We hypothesize that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and test this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected i.p. with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 h for 48 h and sacrificed ~12 h following the last injection. Receptive fields of nociceptors were tested for mechanical, heat, and cold sensitivity. Activity was also measured during an initial 2 min period and during 5 min periods between stimuli. Aberrant activity was common in fibers from morphine-treated mice but rare in salinetreated mice. Resting background activity was elevated in C-fibers from morphinetreated mice. Both C- and Aδ -fibers had afterdischarge in response to mechanical, heat and/or cold stimulation of the skin as well as spontaneous, unevoked activity. Compared to saline, morphine treatment increased the proportion of fibers displaying polymodal rather than mechanical-only responses. A significant increase in Aδ-mechanoreceptive fibers responding to cold accounted for most of this change. In agreement with this, morphine-treated mice showed increased sensitivity in the cold tail flick test. In morphine-treated mice, aberrant activity and hyperexcitability of nociceptors could contribute to increased pain sensitivity. Importantly, this activity is likely driving central sensitization, a phenomenon contributing to abnormal sensory processing and chronic pain. If similar changes occur in human patients, aberrant nociceptor activity is likely to be interpreted as pain, and could contribute to opioid-induced hyperalgesia. PMID:23711478

Development, Validation, and Field-Testing of an Instrument for Clinical Assessment of HIV-Associated Neuropathy and Neuropathic Pain in Resource-Restricted and Large Population Study Settings

PubMed Central

Kamerman, Peter R.; Veliotes, Demetri G. A.; Phillips, Tudor J.; Asboe, David; Boffito, Marta; Rice, Andrew S. C.

2016-01-01

HIV-associated sensory peripheral neuropathy (HIV-SN) afflicts approximately 50% of patients on antiretroviral therapy, and is associated with significant neuropathic pain. Simple accurate diagnostic instruments are required for clinical research and daily practice in both high- and low-resource setting. A 4-item clinical tool (CHANT: Clinical HIV-associated Neuropathy Tool) assessing symptoms (pain and numbness) and signs (ankle reflexes and vibration sense) was developed by selecting and combining the most accurate measurands from a deep phenotyping study of HIV positive people (Pain In Neuropathy Study–HIV-PINS). CHANT was alpha-tested in silico against the HIV-PINS dataset and then clinically validated and field-tested in HIV-positive cohorts in London, UK and Johannesburg, South Africa. The Utah Early Neuropathy Score (UENS) was used as the reference standard in both settings. In a second step, neuropathic pain in the presence of HIV-SN was assessed using the Douleur Neuropathique en 4 Questions (DN4)-interview and a body map. CHANT achieved high accuracy on alpha-testing with sensitivity and specificity of 82% and 90%, respectively. In 30 patients in London, CHANT diagnosed 43.3% (13/30) HIV-SN (66.7% with neuropathic pain); sensitivity = 100%, specificity = 85%, and likelihood ratio = 6.7 versus UENS, internal consistency = 0.88 (Cronbach alpha), average item-total correlation = 0.73 (Spearman’s Rho), and inter-tester concordance > 0.93 (Spearman’s Rho). In 50 patients in Johannesburg, CHANT diagnosed 66% (33/50) HIV-SN (78.8% neuropathic pain); sensitivity = 74.4%, specificity = 85.7%, and likelihood ratio = 5.29 versus UENS. A positive CHANT score markedly increased of pre- to post-test clinical certainty of HIV-SN from 43% to 83% in London, and from 66% to 92% in Johannesburg. In conclusion, a combination of four easily and quickly assessed clinical items can be used to accurately diagnose HIV-SN. DN4-interview used in the context of bilateral feet pain can be used to identify those with neuropathic pain. PMID:27764177

The effect of anxiety sensitivity on psychological and biological variables during the cold pressor test.

PubMed

Dodo, Naomi; Hashimoto, Ryusaku

2017-07-01

We examined the relationship between anxiety sensitivity (AS) and autonomic nervous system responses (ANS) during the cold pressor test (CPT). Seventy-four university students participated and were divided into low-AS (M=9.06, SD=3.97) and high-AS groups (M=28.68, SD=6.63) based on AS Index scores (n's=36 and 38, respectively). The study included three phases: Rest, CPT, and Recovery. We measured the psychological variables (fear of pain and subjective pain) at pre- and post-CPT. ANS response data were collected during each phase. Fear of pain was experienced more strongly in the high-AS group (M=4.74, SD=3.25) relative to the low-AS group (M=2.72, SD=2.31), and subjective pain was also stronger in the high-AS group (M=3.08, SD=1.91) relative to the low-AS group (M=2.47, SD=1.00) in post-CPT. While parasympathetic nervous system (PNS) responses did not differ between the two groups during the CPT, the high AS-group demonstrated lower PNS activity during the Recovery phase. The high-AS group reported significantly more anticipatory fear and pain prior to the CPT, which appeared to aggravate subjective pain experiences. Furthermore, for individuals with anxiety sensitivity, ANS reactivity may be the mechanism underlying the relationship between negative affect and subjective pain. Copyright © 2017. Published by Elsevier B.V.

Value of Examination Under Fluoroscopy for the Assessment of Sacroiliac Joint Dysfunction.

PubMed

Eskander, Jonathan P; Ripoll, Juan G; Calixto, Frank; Beakley, Burton D; Baker, Jeffrey T; Healy, Patrick J; Gunduz, O H; Shi, Lizheng; Clodfelter, Jamie A; Liu, Jinan; Kaye, Alan D; Sharma, Sanjay

2015-01-01

Pain emanating from the sacroiliac (SI) joint can have variable radiation patterns. Single physical examination tests for SI joint pain are inconsistent with multiple tests increasing both sensitivity and specificity. To evaluate the use of fluoroscopy in the diagnosis of SI joint pain. Prospective double blind comparison study. Pain clinic and radiology setting in urban Veterans Administration (VA) in New Orleans, Louisiana. Twenty-two adult men, patients at a southeastern United States VA interventional pain clinic, presented with unilateral low back pain of more than 2 months' duration. Patients with previous back surgery were excluded from the study. Each patient was given a Gapping test, Patrick (FABERE) test, and Gaenslen test. A second blinded physician placed each patient prone under fluoroscopic guidance, asking each patient to point to the most painful area. Pain was provoked by applying pressure with the heel of the palm in that area to determine the point of maximum tenderness. The area was marked with a radio-opaque object and was placed on the mark with a fluoroscopic imgage. A site within 1 cm of the SI joint was considered as a positive test. This was followed by a diagnostic injection under fluoroscopy with 1 mL 2% lidocaine. A positive result was considered as more than 2 hours of greater than 75% reduction in pain. Then, in 2-3 days this was followed by a therapeutic injection under fluoroscopy with 1 mL 0.5% bupivacaine and 40 mg methylprednisolone. Each patient was reassessed after 6 weeks. The sensitivity and specificity in addition to the positive and negative predictive values were determined for both the conventional examinations, as well as the examination under fluoroscopy. Finally, a receiver operating characteristic (ROC) curve was constructed to evaluate test performance. The sensitivity and specificity of the fluoroscopic examination were 0.82 and 0.80 respectively; Positive predictive value and negative predictive value were 0.93 and 0.57 respectively. The area under ROC curve was 0.812 which is considered a "good" test; however the area under ROC for the conventional examination were between 0.52-0.58 which is considered "poor to fail". Variation in anatomy of the SI joint, small sample size. Multiple structures of the SI joint complex can result in clinical symptoms of pain. These include intra-articular structures (degenerative arthritis, and inflammatory conditions) as well as extra-articular structures (ligaments, muscles, etc.).

Muscle Weakness in the Empty and Full Can Tests Cannot Differentiate Rotator Cuff Tear from Cervical Spondylotic Amyotrophy: Pain Provocation is a Useful Finding.

PubMed

Iwata, Eiichiro; Shigematsu, Hideki; Inoue, Kazuya; Egawa, Takuya; Sakamoto, Yoshihiro; Tanaka, Yasuhito

2017-01-01

Rotator cuff tears and cervical spondylotic amyotrophy (CSA) are often confused as the main symptom in those with difficulty in shoulder elevation. Empty and full can tests are frequently used for the clinical diagnosis of rotator cuff tears. The aim of the present study was to investigate whether the empty and full can test results can help differentiate rotator cuff tears from CSA. Twenty-seven consecutive patients with rotator cuff tears and 25 with CSA were enrolled. We prospectively performed empty and full can tests in patients with rotator cuff tears and CSA. The following signs were considered positive: (a) muscle weakness during the empty can test, (b) muscle weakness during the full can test, (c) pain provocation during the empty can test, and (d) pain provocation during the full can test. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of rotator cuff tears for each positive finding. The sensitivity and specificity of each index were as follows (sensitivity, specificity, PPV, NPV): (a) 77.8%, 0%, 45.7%, 0%; (b) 66.7%, 4.0%, 42.9%, 10.0%; (c) 88.9%, 96.0%, 96.0%, 88.9%; and (d) 74.1%, 96.0%, 95.2%, 77.4%. There were significant differences for each index. Muscle weakness during the empty and full can tests was not useful in differentiating rotator cuff tears from CSA because of low specificity and PPV. However, pain provocation was useful in differentiating these two conditions because of high specificity and PPV.

C-reactive protein and cold-pressor tolerance in the general population: the Tromsø Study.

PubMed

Schistad, Elina Iordanova; Stubhaug, Audun; Furberg, Anne-Sofie; Engdahl, Bo Lars; Nielsen, Christopher Sivert

2017-07-01

The aim of this study was to examine whether increases in severity of subclinical inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased experimental pain sensitivity, measured by cold-pressor tolerance, and to test whether this relationship is independent of chronic pain. A large population-based study from 2007 to 2008, the sixth Tromsø Study, provided data from 12,981 participants. For the present analysis, complete data for 10,274 participants (age: median 58 years) were available. The main outcome measure was cold-pressor tolerance, tested by placing the dominant hand in circulating cold water (3°C) for a maximum of 106 seconds. Cox proportional hazard models, treating hand withdrawal during the cold-pressor test as the event and enduring the full test time as censored data, were used to investigate the relationship between hs-CRP levels (≤3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model was controlled for age, sex, education, body mass index, smoking status, alcohol consumption, emotional distress, statin usage, and self-reported presence of chronic pain. Additional analysis was performed in participants without chronic pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance (hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001), adjusted for age and sex. This relationship remained essentially unaltered after controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001), as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001). The present data show that subclinical inflammation is related to increased pain sensitivity, suggesting a potential role of inflammation in experimental pain which may be of importance for the development of clinical pain.

Quantitative Sensory Testing Predicts Pregabalin Efficacy in Painful Chronic Pancreatitis

PubMed Central

Olesen, Søren S.; Graversen, Carina; Bouwense, Stefan A. W.; van Goor, Harry; Wilder-Smith, Oliver H. G.; Drewes, Asbjørn M.

2013-01-01

Background A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. Methods Sixty-four patients with painful chronic pancreatitis received pregabalin (150–300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. Results The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9–1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5–2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. Conclusions The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient’s individual sensory profile and thus comprises a significant step towards personalized pain medicine. PMID:23469256

Association between pain, central sensitization and anxiety in postherpetic neuralgia.

PubMed

Schlereth, T; Heiland, A; Breimhorst, M; Féchir, M; Kern, U; Magerl, W; Birklein, F

2015-02-01

In postherpetic neuralgia (PHN), dorsal root ganglia neurons are damaged. According to the proposed models, PHN pain might be associated with nociceptive deafferentation, and peripheral (heat hyperalgesia) or central sensitization (allodynia). In 36 PHN patients, afferent nerve fibre function was characterized using quantitative sensory testing and histamine-induced flare analysis. Psychological factors were evaluated with the Hospital Anxiety and Depression Scale (HADS), disease-related quality of life (QoL) with SF-36 and pain with the McGill questionnaire [pain rating index (PRI)]. The patients were also divided into subgroups according to the presence or absence of brush-evoked allodynia as a sign of central sensitization. For all patients, warm, cold and mechanical detection was impaired (p < 0.001 each) and the size of the histamine flare was diminished on the affected side (p < 0.05); pain thresholds with the exception of brush-evoked allodynia (p < 0.05) were unaltered. Correlation analysis revealed allodynia, anxiety, depression, QoL and age as relevant factors associated with pain severity (PRI). Allodynia was present in 23 patients (64%). In these patients, heat pain perception was preserved; the histamine flare was larger; the pinprick pain was increased as were McGill PRI sensory subscore, actual pain rating and almost significantly pain (McGill PRI) over the last 4 weeks. PHN is associated with damage of afferent fibres. Central sensitization (i.e., allodynia) might contribute to PHN pain. There was a striking association between anxiety, depression and age, and the magnitude of PHN pain. © 2014 European Pain Federation - EFIC®

Hyperalgesia and Persistent Pain after Breast Cancer Surgery: A Prospective Randomized Controlled Trial with Perioperative COX-2 Inhibition

PubMed Central

van Helmond, Noud; Steegers, Monique A.; Filippini-de Moor, Gertie P.; Vissers, Kris C.; Wilder-Smith, Oliver H.

2016-01-01

Background Persistent pain is a challenging clinical problem after breast cancer treatment. After surgery, inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain. Using quantitative sensory testing, we tested the hypothesis that adding COX-2 inhibition to standard treatment reduces hyperalgesia after breast cancer surgery. A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia. Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were randomized to COX-2 inhibition (2x40mg parecoxib on day of surgery, thereafter 2x200mg celecoxib/day until day five) or placebo. Preoperatively and 1, 5, 15 days and 1, 3, 6, 12 months postoperatively, we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100mm VAS score for pain. We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication. To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months. Results 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis. Contrary to our primary hypothesis, change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo. COX-2 inhibition had an effect on pain on movement at postoperative day 5 (p<0.01). Consistent with our secondary hypothesis, change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain (p<0.01) from day 5 to 1 year postoperatively. Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery. Central sensitization may play a role in the genesis of persistent postsurgical pain. PMID:27935990

Effects of vicarious pain on self-pain perception: investigating the role of awareness

PubMed Central

Terrighena, Esslin L; Lu, Ge; Yuen, Wai Ping; Lee, Tatia MC; Keuper, Kati

2017-01-01

The observation of pain in others may enhance or reduce self-pain, yet the boundary conditions and factors that determine the direction of such effects are poorly understood. The current study set out to show that visual stimulus awareness plays a crucial role in determining whether vicarious pain primarily activates behavioral defense systems that enhance pain sensitivity and stimulate withdrawal or appetitive systems that attenuate pain sensitivity and stimulate approach. We employed a mixed factorial design with the between-subject factors exposure time (subliminal vs optimal) and vicarious pain (pain vs no pain images), and the within-subject factor session (baseline vs trial) to investigate how visual awareness of vicarious pain images affects subsequent self-pain in the cold-pressor test. Self-pain tolerance, intensity and unpleasantness were evaluated in a sample of 77 healthy participants. Results revealed significant interactions of exposure time and vicarious pain in all three dependent measures. In the presence of visual awareness (optimal condition), vicarious pain compared to no-pain elicited overall enhanced self-pain sensitivity, indexed by reduced pain tolerance and enhanced ratings of pain intensity and unpleasantness. Conversely, in the absence of visual awareness (subliminal condition), vicarious pain evoked decreased self-pain intensity and unpleasantness while pain tolerance remained unaffected. These findings suggest that the activation of defense mechanisms by vicarious pain depends on relatively elaborate cognitive processes, while – strikingly – the appetitive system is activated in highly automatic manner independent from stimulus awareness. Such mechanisms may have evolved to facilitate empathic, protective approach responses toward suffering individuals, ensuring survival of the protective social group. PMID:28831270

[Nootropic and analgesic effects of Semax following different routes of administration].

PubMed

Manchenko, D M; Glazova, N Iu; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F

2010-10-01

Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.

Diagnostic Accuracy of the Neck Tornado Test as a New Screening Test in Cervical Radiculopathy.

PubMed

Park, Juyeon; Park, Woo Young; Hong, Seungbae; An, Jiwon; Koh, Jae Chul; Lee, Youn-Woo; Kim, Yong Chan; Choi, Jong Bum

2017-01-01

The Spurling test, although a highly specific provocative test of the cervical spine in cervical radiculopathy (CR), has low to moderate sensitivity. Thus, we introduced the neck tornado test (NTT) to examine the neck and the cervical spine in CR. The aim of this study was to introduce a new provocative test, the NTT, and compare the diagnostic accuracy with a widely accepted provocative test, the Spurling test. Retrospective study. Medical records of 135 subjects with neck pain (CR, n = 67; without CR, n = 68) who had undergone cervical spine magnetic resonance imaging and been referred to the pain clinic between September 2014 and August 2015 were reviewed. Both the Spurling test and NTT were performed in all patients by expert examiners. Sensitivity, specificity, and accuracy were compared for both the Spurling test and the NTT. The sensitivity of the Spurling test and the NTT was 55.22% and 85.07% ( P < 0.0001); specificity, 98.53% and 86.76% ( P = 0.0026); accuracy, 77.04% and 85.93% ( P = 0.0423), respectively. The NTT is more sensitive with superior diagnostic accuracy for CR diagnosed by magnetic resonance imaging than the Spurling test.

Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli

PubMed Central

Dixon, Eric A.; Benham, Grant; Sturgeon, John A.; Mackey, Sean; Johnson, Kevin A.; Younger, Jarred

2016-01-01

Sensory hypersensitivity is one manifestation of the central sensitization that may underlie conditions such as fibromyalgia and chronic fatigue syndrome. We conducted five studies designed to develop and validate the Sensory Hypersensitive Scale (SHS); a 25-item self-report measure of sensory hypersensitivity. The SHS assesses both general sensitivity and modality-specific sensitivity (e.g. touch, taste, and hearing). 1202 participants (157 individuals with chronic pain) completed the SHS, which demonstrated an adequate overall internal reliability (Cronbach’s alpha) of 0.81, suggesting the tool can be used as a cross-modality assessment of sensitivity. SHS scores demonstrated only modest correlations (Pearson’s r) with depressive symptoms (0.19) and anxiety (0.28), suggesting a low level of overlap with psychiatric complaints. Overall SHS scores showed significant but relatively modest correlations (Pearson’s r) with three measures of sensory testing: cold pain tolerance (−0.34); heat pain tolerance (−0.285); heat pain threshold (−0.271). Women reported significantly higher scores on the SHS than did men, although gender-based differences were small. In a chronic pain sample, individuals with fibromyalgia syndrome demonstrated significantly higher SHS scores than did individuals with osteoarthritis or back pain. The SHS appears suitable as a screening measure for sensory hypersensitivity, though additional research is warranted to determine its suitability as a proxy for central sensitization. PMID:26873609

Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors.

PubMed

Tamano, Ryuta; Ishida, Mitsuhiro; Asaki, Toshiyuki; Hasegawa, Minoru; Shinohara, Shunji

2016-02-26

Dysfunction in the central serotonin (5-HT) and norepinephrine (NE) systems cause depression and pain. Descending spinal pain modulatory pathways are important in the analgesic mechanisms of antidepressants, particularly serotonin and norepinephrine reuptake inhibitors (SNRIs). While many non-clinical studies have demonstrated the roles of central monoaminergic systems in pain, there is little evidence to illuminate the direct contribution of spinal descending pain modulatory systems independently of depressive-like behavior. To examine the effects of dysfunction of spinal monoaminergic systems on pain sensitivity, we established a rat chronic pain model by administering lumbar-intrathecal reserpine to minimize its influence on brain. Lumbar-intrathecal reserpine evoked persistent mechanical hypersensitivity and corresponding reductions in spinal 5-HT and NE concentrations (from 767.2 to 241.6ng/g and from 455.9 to 41.7ng/g, respectively after reserpine 30nmol). Lumbar-intrathecal reserpine did not deplete brain monoamines or bring about depressive-like behavior in the forced swim test. Spinal monoamines depletion-induced pain sensitivity was ameliorated by lumbar-intrathecal administration of the SNRIs (duloxetine and milnacipran) in dose-dependent manners. These suggest that increased pain sensitivity could be induced by dysfunction solely of the descending pain modulatory system, regardless of depressive-like behavior, and lumbar-intrathecal administration of SNRIs could ameliorate the pain sensitivity which might be mediated by affecting the descending pain modulatory system in the spinal cord, not via their antidepressant effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association of hip pain with radiographic evidence of hip osteoarthritis: diagnostic test study

PubMed Central

Nevitt, Michael C; Niu, Jingbo; Clancy, Mary M; Lane, Nancy E; Link, Thomas M; Vlad, Steven; Tolstykh, Irina; Jungmann, Pia M.; Felson, David T; Guermazi, Ali

2015-01-01

Study question Is there concordance between hip pain and radiographic hip osteoarthritis? Methods In this diagnostic test study, pelvic radiographs were assessed for hip osteoarthritis in two cohorts: the Framingham Osteoarthritis Study (community of Framingham, Massachusetts) and the Osteoarthritis Initiative (a multicenter longitudinal cohort study of osteoarthritis in the United States). Using visual representation of the hip joint, participants reported whether they had hip pain on most days and the location of the pain: anterior, groin, lateral, buttocks, or low back. In the Framingham study, participants with hip pain were also examined for hip pain with internal rotation. The authors analysed the agreement between radiographic hip osteoarthritis and hip pain, and for those with hip pain suggestive of hip osteoarthritis they calculated the sensitivity, specificity, positive predictive value, and negative predictive value of radiographs as the diagnostic test. Study answer and limitations In the Framingham study (n=946), only 15.6% of hips in patients with frequent hip pain showed radiographic evidence of hip osteoarthritis, and 20.7% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of radiographic hip osteoarthritis for hip pain localised to the groin was 36.7%, specificity 90.5%, positive predictive value 6.0%, and negative predictive value 98.9%. Results did not differ much for hip pain at other locations or for painful internal rotation. In the Osteoarthritis Initiative study (n=4366), only 9.1% of hips in patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of definite radiographic hip osteoarthritis for hip pain localised to the groin was 16.5%, specificity 94.0%, positive predictive value 7.1%, and negative predictive value 97.6%. Results also did not differ much for hip pain at other locations. What this study adds Hip pain was not present in many hips with radiographic osteoarthritis, and many hips with pain did not show radiographic hip osteoarthritis. Most older participants with a high suspicion for clinical hip osteoarthritis (groin or anterior pain and/or painful internal rotation) did not have radiographic hip osteoarthritis, suggesting that in many cases, hip osteoarthritis might be missed if diagnosticians relied solely on hip radiographs. Funding, competing interests, data sharing See the full paper on thebmj.com for funding. The authors have no competing interests. Additional data are available from bevochan@bu.edu. PMID:26631296

Pavlovian second-order conditioned analgesia.

PubMed

Ross, R T

1986-01-01

Three experiments with rat subjects assessed conditioned analgesia in a Pavlovian second-order conditioning procedure by using inhibition of responding to thermal stimulation as an index of pain sensitivity. In Experiment 1, rats receiving second-order conditioning showed longer response latencies during a test of pain sensitivity in the presence of the second-order conditioned stimulus (CS) than rats receiving appropriate control procedures. Experiment 2 found that extinction of the first-order CS had no effect on established second-order conditioned analgesia. Experiment 3 evaluated the effects of post second-order conditioning pairings of morphine and the shock unconditioned stimulus (US). Rats receiving paired morphine-shock presentations showed significantly shorter response latencies during a hot-plate test of pain sensitivity in the presence of the second-order CS than did groups of rats receiving various control procedures; second-order analgesia was attenuated. These data extend the associative account of conditioned analgesia to second-order conditioning situations and are discussed in terms of the mediation of both first- and second-order analgesia by an association between the CS and a representation or expectancy of the US, which may directly activate endogenous pain inhibition systems.

It's time to change perspective! New diagnostic tools for lateral elbow pain.

PubMed

Arrigoni, P; Cucchi, D; Menon, A; Randelli, P

2017-12-01

The presence of intra-articular findings that may complement the extra-articular pathology in lateral epicondilytis has been suggested, and a role for minor instability of the elbow as part of the causative process of this disease has been postulated. This study was designed to describe two new clinical tests, aimed at detecting intra-articular pathology in patients affected by recalcitrant lateral epicondylitis and investigate their diagnostic performance. Ten patients suffering of atraumatic lateral elbow pain unresponsive to conservative treatment were considered in this study. Two clinical tests were developed and administrated prior to arthroscopy: Supination and Antero-Lateral pain Test (SALT); Posterior Elbow Pain by Palpation-Extension of the Radiocapitellar joint (PEPPER). Sensitivity, specificity, predictive values and accuracy of SALT and PEPPER as diagnostic tests for seven intra-articular findings were calculated. In 90% of the patients, at least one test was positive. All patients with signs of lateral ligamentous patholaxity or intra-articular abnormal findings had a positive response to at least one of the two tests. SALT proved to have a high sensitivity but a low specificity and is accurate in detecting the presence of intra-articular abnormal findings, especially synovitis. PEPPER test was sensible, specific and accurate in the detection of radial head chondropathy. Two new diagnostic tests (SALT and PEPPER) were specifically designed to evoke pain from intra-articular structures. These tests could be a valid support in the diagnostic algorithm of recalcitrant lateral elbow pain. Positive findings may be indicative of a minor instability of the lateral elbow condition. Diagnostic study, development of diagnostic criteria on basis of consecutive patients, level II.

An Improved Model of Heat-Induced Hyperalgesia—Repetitive Phasic Heat Pain Causing Primary Hyperalgesia to Heat and Secondary Hyperalgesia to Pinprick and Light Touch

PubMed Central

Henrich, Florian; Magerl, Walter; May, Arne

2014-01-01

This study tested a modified experimental model of heat-induced hyperalgesia, which improves the efficacy to induce primary and secondary hyperalgesia and the efficacy-to-safety ratio reducing the risk of tissue damage seen in other heat pain models. Quantitative sensory testing was done in eighteen healthy volunteers before and after repetitive heat pain stimuli (60 stimuli of 48°C for 6 s) to assess the impact of repetitive heat on somatosensory function in conditioned skin (primary hyperalgesia area) and in adjacent skin (secondary hyperalgesia area) as compared to an unconditioned mirror image control site. Additionally, areas of flare and secondary hyperalgesia were mapped, and time course of hyperalgesia determined. After repetitive heat pain conditioning we found significant primary hyperalgesia to heat, and primary and secondary hyperalgesia to pinprick and to light touch (dynamic mechanical allodynia). Acetaminophen (800 mg) reduced pain to heat or pinpricks only marginally by 11% and 8%, respectively (n.s.), and had no effect on heat hyperalgesia. In contrast, the areas of flare (−31%) and in particular of secondary hyperalgesia (−59%) as well as the magnitude of hyperalgesia (−59%) were significantly reduced (all p<0.001). Thus, repetitive heat pain induces significant peripheral sensitization (primary hyperalgesia to heat) and central sensitization (punctate hyperalgesia and dynamic mechanical allodynia). These findings are relevant to further studies using this model of experimental heat pain as it combines pronounced peripheral and central sensitization, which makes a convenient model for combined pharmacological testing of analgesia and anti-hyperalgesia mechanisms related to thermal and mechanical input. PMID:24911787

Thermoreception and nociception of the skin: a classic paper of Bessou and Perl and analyses of thermal sensitivity during a student laboratory exercise.

PubMed

Kuhtz-Buschbeck, Johann P; Andresen, Wiebke; Göbel, Stephan; Gilster, René; Stick, Carsten

2010-06-01

About four decades ago, Perl and collaborators were the first ones who unambiguously identified specifically nociceptive neurons in the periphery. In their classic work, they recorded action potentials from single C-fibers of a cutaneous nerve in cats while applying carefully graded stimuli to the skin (Bessou P, Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025-1043, 1969). They discovered polymodal nociceptors, which responded to mechanical, thermal, and chemical stimuli in the noxious range, and differentiated them from low-threshold thermoreceptors. Their classic findings form the basis of the present method that undergraduate medical students experience during laboratory exercises of sensory physiology, namely, quantitative testing of the thermal detection and pain thresholds. This diagnostic method examines the function of thin afferent nerve fibers. We collected data from nearly 300 students that showed that 1) women are more sensitive to thermal detection and thermal pain at the thenar than men, 2) habituation shifts thermal pain thresholds during repetititve testing, 3) the cold pain threshold is rather variable and lower when tested after heat pain than in the reverse case (order effect), and 4) ratings of pain intensity on a visual analog scale are correlated with the threshold temperature for heat pain but not for cold pain. Median group results could be reproduced in a retest. Quantitative sensory testing of thermal thresholds is feasible and instructive in the setting of a laboratory exercise and is appreciated by the students as a relevant and interesting technique.

Nicotine withdrawal and stress-induced changes in pain sensitivity: a cross-sectional investigation between abstinent smokers and nonsmokers.

PubMed

Nakajima, Motohiro; Al'Absi, Mustafa

2014-10-01

Chronic smoking has been linked with alterations in endogenous pain regulation. These alterations may be pronounced when individuals quit smoking because nicotine withdrawal produces a variety of psychological and physiological symptoms. Smokers interested in quitting (n = 98) and nonsmokers (n = 37) completed a laboratory session including cold pressor test (CPT) and heat thermal pain. Smokers set a quit date and completed the session after 48 h of abstinence. Participants completed the pain assessments once after rest and once after stress. Cardiovascular and nicotine withdrawal measures were collected. Smokers showed blunted cardiovascular responses to stress relative to nonsmokers. Only nonsmokers had greater pain tolerance to CPT after stress than after rest. Lower systolic blood pressure was related to lower pain tolerance. These findings suggest that smoking withdrawal is associated with blunted stress response and increased pain sensitivity. Copyright © 2014 Society for Psychophysiological Research.

Sex Differences in Experimental and Clinical Pain Sensitivity for Patients with Shoulder Pain

PubMed Central

Kindler, Lindsay L.; Valencia, Carolina; Fillingim, Roger B.; George, Steven Z.

2010-01-01

Previous research demonstrates that men and women differ in the way that they perceive and process pain. Much of this work has been done in healthy adults with a lack of consensus in clinical pain populations. The purpose of this study was to investigate how men and women with shoulder pain differ in their experience of experimental and clinical pain and whether psychological processes differentially affect these responses. Fifty nine consecutive subjects (24 women, 35 men) seeking operative treatment for shoulder pain were enrolled in this study. Subjects completed self report questionnaires to assess clinical pain, catastrophizing, anxiety and depression and underwent a series of experimental pain tests consisting of pressure pain, thermal pain (threshold and tolerance), and thermal temporal summation. Results indicated that women experienced greater clinical pain and enhanced sensitivity to pressure pain. Age did not affect the observed sex differences. There were no sex differences in psychological association with experimental and clinical pain in this cohort. The relationship between clinical and experimental pressure pain was stronger in women as compared to men. These findings offer insight into the interactions between biological and psychosocial influences of pain and how these interactions vary by sex. PMID:20598598

Ethnic differences in physical pain sensitivity: role of acculturation.

PubMed

Chan, Michelle Y P; Hamamura, Takeshi; Janschewitz, Kristin

2013-01-01

Although research suggests that Asian Americans are more reactive to physical pain than European Americans, some evidence suggests that the observed differences in ethnicity may actually reflect Asian Americans' differing levels of acculturation. Two studies were conducted to test this hypothesis. In Study 1, first- and second-generation Asian Americans and European Americans took part in a cold pressor task. Evidence of heightened pain responses was found only among first-generation Asian Americans. Study 2 further controlled for ethnicity and replicated this pattern in finding heightened pain reactions among mainland Chinese students in Hong Kong relative to Hong Kong Chinese students. These findings suggest a role for acculturation in accounting for ethnic differences in physical pain sensitivity. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Comparison of the Analgesic Effects of Dronabinol and Smoked Marijuana in Daily Marijuana Smokers

PubMed Central

Cooper, Ziva D; Comer, Sandra D; Haney, Margaret

2013-01-01

Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain, yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ9-tetrahydrocannabinol (THC; dronabinol). This randomized, placebo-controlled, double-dummy, double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a validated experimental model of pain. Healthy male (N=15) and female (N=15) daily marijuana smokers participated in this outpatient study comparing the analgesic, subjective, and physiological effects of marijuana (0.00, 1.98, or 3.56% THC) to dronabinol (0, 10, or 20 mg). Pain response was assessed using the cold-pressor test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded. Subjective pain and drug effect ratings were also measured as well as cardiovascular effects. Compared with placebo, marijuana and dronabinol decreased pain sensitivity (3.56% 20 mg), increased pain tolerance (1.98% 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56% 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, although dronabinol produced analgesia that was of a longer duration. Marijuana (1.98, 3.56%) and dronabinol (20 mg) also increased abuse-related subjective ratings relative to placebo; these ratings were greater with marijuana. These data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana. PMID:23609132

Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and β-endorphin.

PubMed

Nuseir, Khawla Q; Alzoubi, Karem H; Alhusban, Ahmed; Bawaane, Areej; Al-Azzani, Mohammed; Khabour, Omar F

2017-10-01

Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers.

PubMed

Cooper, Ziva D; Comer, Sandra D; Haney, Margaret

2013-09-01

Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain, yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ(9)-tetrahydrocannabinol (THC; dronabinol). This randomized, placebo-controlled, double-dummy, double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a validated experimental model of pain. Healthy male (N=15) and female (N=15) daily marijuana smokers participated in this outpatient study comparing the analgesic, subjective, and physiological effects of marijuana (0.00, 1.98, or 3.56% THC) to dronabinol (0, 10, or 20 mg). Pain response was assessed using the cold-pressor test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded. Subjective pain and drug effect ratings were also measured as well as cardiovascular effects. Compared with placebo, marijuana and dronabinol decreased pain sensitivity (3.56%; 20 mg), increased pain tolerance (1.98%; 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56%; 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, although dronabinol produced analgesia that was of a longer duration. Marijuana (1.98, 3.56%) and dronabinol (20 mg) also increased abuse-related subjective ratings relative to placebo; these ratings were greater with marijuana. These data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana.

Reduced laser-evoked potential habituation detects abnormal central pain processing in painful radiculopathy patients.

PubMed

Hüllemann, P; von der Brelie, C; Manthey, G; Düsterhöft, J; Helmers, A K; Synowitz, M; Baron, R

2017-05-01

Repetitive painful laser stimuli lead to physiological laser-evoked potential (LEP) habituation, measurable by a decrement of the N2/P2 amplitude. The time course of LEP-habituation is reduced in the capsaicin model for peripheral and central sensitization and in patients with migraine and fibromyalgia. In the present investigation, we aimed to assess the time course of LEP-habituation in a neuropathic pain syndrome, i.e. painful radiculopathy. At the side of radiating pain, four blocks of 25 painful laser stimuli each were applied to the ventral thigh at the L3 dermatome in 27 patients with painful radiculopathy. Inclusion criteria were (1) at least one neurological finding of radiculopathy, (2) low back pain with radiation into the foot and (3) a positive one-sided compression of the L5 and/or S1 root in the MRI. The time course of LEP-habituation was compared to 20 healthy height and age matched controls. Signs of peripheral (heat hyperalgesia) and central sensitization (dynamic mechanical allodynia and hyperalgesia) at the affected L5 or S1 dermatome were assessed with quantitative sensory testing. Painful radiculopathy patients showed decreased LEP-habituation compared to controls. Patients with signs of central sensitization showed a more prominent LEP-habituation decrease within the radiculopathy patient group. Laser-evoked potential habituation is reduced in painful radiculopathy patients, which indicates an abnormal central pain processing. Central sensitization seems to be a major contributor to abnormal LEP habituation. The LEP habituation paradigm might be useful as a clinical tool to assess central pain processing alterations in nociceptive and neuropathic pain conditions. Abnormal central pain processing in neuropathic pain conditions may be revealed with the laser-evoked potential habituation paradigm. In painful radiculopathy patients, LEP-habituation is reduced compared to healthy controls. © 2017 European Pain Federation - EFIC®.

Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

PubMed

Iacovides, S; Avidon, I; Baker, F C

2015-07-01

Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p < 0.01] and follicular [dysmenorrhoeics vs. controls mean (SD): 60 (18) mm vs. 40 (14) mm, p < 0.01] phases of the menstrual cycle. These data show that compared with controls, women who experience severe recurrent dysmenorrhoea have deep-tissue hyperalgesia to ischaemic pain in muscles outside of the referred area of menstrual pain both during the painful menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

The sensitivity and specificity of the Slump and the Straight Leg Raising tests in patients with lumbar disc herniation.

PubMed

Majlesi, Javid; Togay, Halit; Unalan, Halil; Toprak, Sadk

2008-04-01

An accurate and specific diagnosis prevents the recurrences of low back pain and chronic spinal pain. The physical examination is the most useful tool to diagnosis. The examiner must aim to determine the exact tissue that pain arises from to make the specific diagnosis. Lumbar disc herniation is 1 disease that physical examination, symptoms, and findings on imaging technique do not always correlate with each other. The Straight Leg Raising (SLR) test has been used as the primary test to diagnosis lumbar disc herniations and found to have high correlation with findings on operation since its sensitivity is high in only disc herniations leading to root compression that may eventually need operation. More sensitive test, like the Slump, might be used in herniations in which the SLR is negative. The Slump test is really a variant of the SLR and the Lasègue's tests performed in the seated position and is a progressive series of maneuvers designed to place the sciatic nerve roots under increasing tension. At each step in the procedure, the patient informs the examiner what is being felt and whether radicular pain is produced. As a result, the Slump test applies traction to the nerve roots by incorporating spinal and hip joint flexion into the leg raising and would warn the examiner of the presence of nerve root compression when there is a negative SLR test. This study measured the sensitivity and specificity of the Slump test and compare it with the SLR test in patients with and without lumbar disc herniations. A prospective case control study of 75 patients with complaints suggestive of lumbar disc herniation was carried out in the outpatient clinics of the neurosurgery department of a state teaching hospital. Seventy-five referred or self-admitted patients with low back, leg, or low back and leg pain who had results of magnetic resonance imaging (MRI) of the lumbar spine were included in the study. Thirty-eight patients had signs of herniation demonstrated by MRI. Control patients (n = 37) had no disc bulges or herniations on MRI. Both the Slump and SLR tests were performed during the assessment of all the patients by the second author. The MRI results were assessed and recorded by the first author. The Slump test was found to be more sensitive (0.84) than the SLR (0.52) in the patients with lumbar disc herniations. However, the SLR was found to be a slightly more specific test (0.89) than the Slump test (0.83). The Slump test might be used more frequently as a sensitive physical examination tool in patients with symptoms of lumbar disc herniations. In contrast, owing to its higher specificity, the SLR test may especially help identify patients who have herniations with root compression requiring surgery.

Validity, Sensitivity, and Responsiveness of the 11-Face Faces Pain Scale to Postoperative Pain in Adult Orthopedic Surgery Patients.

PubMed

Van Giang, Nguyen; Chiu, Hsiao-Yean; Thai, Duong Hong; Kuo, Shu-Yu; Tsai, Pei-Shan

2015-10-01

Pain is common in patients after orthopedic surgery. The 11-face Faces Pain Scale has not been validated for use in adult patients with postoperative pain. To assess the validity of the 11-face Faces Pain Scale and its ability to detect responses to pain medications, and to determine whether the sensitivity of the 11-face Faces Pain Scale for detecting changes in pain intensity over time is associated with gender differences in adult postorthopedic surgery patients. The 11-face Faces Pain Scale was translated into Vietnamese using forward and back translation. Postoperative pain was assessed using an 11-point numerical rating scale and the 11-face Faces Pain Scale on the day of surgery, and before (Time 1) and every 30 minutes after (Times 2-5) the patients had taken pain medications on the first postoperative day. The 11-face Faces Pain Scale highly correlated with the numerical rating scale (r = 0.78, p < .001). When the scores from each follow-up test (Times 2-5) were compared with those from the baseline test (Time 1), the effect sizes were -0.70, -1.05, -1.20, and -1.31, and the standardized response means were -1.17, -1.59, -1.66, and -1.82, respectively. The mean change in pain intensity, but not gender-time interaction effect, over the five time points was significant (F = 182.03, p < .001). Our results support that the 11-face Faces Pain Scale is appropriate for measuring acute postoperative pain in adults. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

[Comparison between gastric and esophageal mechano-sensitivity in patients with functional dyspepsia].

PubMed

López Gastón, A R; López De Luise, G A; Andrüsh, A

1996-01-01

Patients with non ulcer dyspepsia (NUD) and lowered mechano sensitivity thresholds in stomach may have lowered mechano sensitivity thresholds in oesophagus also. The aim was to check this hypothesis. 39 patients with NUD (11 men and 24 women, mean age 57 years, SEM 3.72, range 17-86) and 20 controls (10 men, 10 women, mean age 49.3 years, SEM 3.72, range 31-66) were studied. Organis diseases were discarded. Gastric mechano sensitivity was studied with a latex balloon of low compliance, 8 cm length, connected to a manometer. Balloon was inflated "in ramp" at 10 ml/sec, and "first sensation", discomfort", and "pain" were registered. At 900 ml inflation was stopped if pain was not evoked. Oesophageal mechano sensitivity was studied with another latex balloon of low compliance which, after inflated with 15 ml. of air, was 3.5 cm. in diameter. Esophageal balloon was inflated "in ramp" (1 ml/sec) up 15 ml. and deflated in 2 cm step from 36 to 22 cm from SDA. Inflation was stopped when symptoms (pain or discomfort were evoked. Oesophageal acid perfusion test was performed. 83.4% of controls completed up 700 ml. of gastric distension vs. 35.9% of patients with NUD (p > 0.001). No significative differences in intra-balloon pressure slope were observed between both groups. 79.2% of NUD patients had chest pain with oesophageal ballon distension = < 7 ml. vs. 5% in controls (p > 0.001). Mean volumes were 7.03 ml. (NUD) and 11.9% (controls) (p = 0.001), 63% of dyspeptic patients with lowered gastric sensitivity thresholds (< 700 ml) had oesophagic symptoms with inflation volumes = < 7 ml. There was a positive correlation in stomach and oesophageal mechano sensitivities variations (r = 0.75, +/- 0.58, p > 0.01). When analyzed with that results, oesophageal acid perfusion test showed 38.5% of "mixed sensitivities" (both mechano- and chemo-), 30.7% of "mechano sensorials" (negative acid test, positive balloon test), and 10.3% of :chemo sensorials" (positive acid test only). In 20.5% both tests were normal at the moment they were done. These results agreed with our previous experiences in oesophagus. It was concluded that a significative proportion of NUD patients had lowered thresholds for mechano stimulation of stomach and oesophagus at the time that both tests were done. Such alterations support the hypothesis that a more general mechano-sensitivity alteration is present in patients with NUD.

Clinical examination and physical assessment of hip joint-related pain in athletes.

PubMed

Reiman, Michael P; Thorborg, Kristian

2014-11-01

Evidence-based clinical examination and assessment of the athlete with hip joint related pain is complex. It requires a systematic approach to properly differentially diagnose competing potential causes of athletic pain generation. An approach with an initial broad focus (and hence use of highly sensitive tests/measures) that then is followed by utilizing more specific tests/measures to pare down this imprecise differential diagnosis list is suggested. Physical assessment measures are then suggested to discern impairments, activity and participation restrictions for athletes with hip-join related pain, hence guiding the proper treatment approach. 5.

Altered pressure pain thresholds and increased wind-up in adult patients with chronic back pain with a history of childhood maltreatment: a quantitative sensory testing study.

PubMed

Tesarz, Jonas; Eich, Wolfgang; Treede, Rolf-Detlef; Gerhardt, Andreas

2016-08-01

Childhood maltreatment (CM) has been associated with an increased risk of nonspecific chronic low back pain (nsCLBP). However, the mechanisms underlying this association are unclear. Therefore, this study considered whether distinct types of CM are accompanied by specific alterations in somatosensory function. A total of 176 subjects with nsCLBP and 27 pain-free controls (PCs) were included. The Childhood Trauma Questionnaire (CTQ) was used to categorize patients into 2 groups (abused/neglected vs nonabused/nonneglected) for 5 types of CM (emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect). The standardized quantitative sensory testing protocol of the "German Research Network on Neuropathic Pain" was performed to obtain comprehensive profiles on somatosensory function, including detection and pain thresholds, pain sensitivity, and assessments of temporal summation (wind-up). Between 17.7% and 51.4% of subjects with nsCLBP reported CM, depending on the type of CM. Childhood Trauma Questionnaire subscores for emotional and sexual abuse were significantly higher in subjects with nsCLBP than in PCs. Compared with PCs, subjects with CM showed reduced pressure pain thresholds (PPTs), irrespective of the type of CM. Regarding distinct types of CM, subjects with nsCLBP with emotional abuse reported significantly higher wind-up than those without, and sexual abuse was accompanied by enhanced touch sensitivity. Our findings suggest that CM is nonspecifically associated with a decreased PPT in nsCLBP. Emotional abuse apparently leads to enhanced spinal pain summation, and sexual abuse leads to enhanced touch sensitivity. These results emphasize the importance of emotional abuse in nsCLBP and suggest that CM can induce long-term changes in adult somatosensory function.

Nervous System Sensitization as a Predictor of Outcome in the Treatment of Peripheral Musculoskeletal Conditions: A Systematic Review.

PubMed

O'Leary, Helen; Smart, Keith M; Moloney, Niamh A; Doody, Catherine M

2017-02-01

Research suggests that peripheral and central nervous system sensitization can contribute to the overall pain experience in peripheral musculoskeletal (MSK) conditions. It is unclear, however, whether sensitization of the nervous system results in poorer outcomes following the treatment. This systematic review investigated whether nervous system sensitization in peripheral MSK conditions predicts poorer clinical outcomes in response to a surgical or conservative intervention. Four electronic databases were searched to identify the relevant studies. Eligible studies had a prospective design, with a follow-up assessing the outcome in terms of pain or disability. Studies that used baseline indices of nervous system sensitization were included, such as quantitative sensory testing (QST) or questionnaires that measured centrally mediated symptoms. Thirteen studies met the inclusion criteria, of which six were at a high risk of bias. The peripheral MSK conditions investigated were knee and hip osteoarthritis, shoulder pain, and elbow tendinopathy. QST parameters indicative of sensitization (lower electrical pain thresholds, cold hyperalgesia, enhanced temporal summation, lower punctate sharpness thresholds) were associated with negative outcome (more pain or disability) in 5 small exploratory studies. Larger studies that accounted for multiple confounders in design and analysis did not support a predictive relationship between QST parameters and outcome. Two studies used self-report measures to capture comorbid centrally mediated symptoms, and found higher questionnaire scores were independently predictive of more persistent pain following a total joint arthroplasty. This systematic review found insufficient evidence to support an independent predictive relationship between QST measures of nervous system sensitization and treatment outcome. Self-report measures demonstrated better predictive ability. Further high-quality prognostic research is warranted. © 2016 World Institute of Pain.

The application of neuropathic pain questionnaires in burning mouth syndrome patients.

PubMed

Heo, Jun-Young; Ok, Soo-Min; Ahn, Yong-Woo; Ko, Myung-Yun; Jeong, Sung-Hee

2015-01-01

To evaluate and compare the validity of the PainDETECT, DN4, and abbreviated DN4 (DN4i) neuropathic pain questionnaires for primary burning mouth syndrome (BMS), which is a burning sensation in the oral mucosa in the absence of any identifiable organic etiology. Eighty-one patients (42 with primary BMS and 39 with nociceptive pain) complaining of a burning sensation and pain in their oral mucosa were enrolled in this study. All of the patients completed the neuropathic pain questionnaires. The sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic (ROC) curve were estimated. Then the relationship between pain intensity and total neuropathic pain score was investigated. Data were analyzed with the chi-square test and independent t test for subjects' baseline characteristic differences, and with Pearson correlation coefficients for the relationship of variables. The mean area under the ROC curves (AUCs) for PainDETECT, DN4, and DN4i were 0.81, 0.79, and 0.81, respectively. There was no statistically significant difference in the AUCs among the questionnaires. PainDETECT, DN4, and DN4i had a lower sensitivity and specificity for BMS compared to previous validation studies. The total scores for PainDETECT, DN4, and DN4i in the primary BMS group were significantly associated with pain intensity. Although the results of this study suggest that neuropathic pain questionnaires, such as PainDETECT and DN4, are not ideal principal screening tools for BMS patients, a substantial proportion of neuropathic symptoms in primary BMS patients were identified.

Pain Sensitivity Subgroups in Individuals With Spine Pain: Potential Relevance to Short-Term Clinical Outcome

PubMed Central

Bialosky, Joel E.; Robinson, Michael E.

2014-01-01

Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm these findings. PMID:24764070

Multiple Levels of Suffering

PubMed Central

Kiley, Kasey B.; Haywood, Carlton; Bediako, Shawn M.; Lanzkron, Sophie; Carroll, C. Patrick; Buenaver, Luis F.; Pejsa, Megan; Edwards, Robert R.; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Objective: People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Methods: Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Results: Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Discussion: Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology. PMID:26889615

The effect of culture on pain sensitivity.

PubMed

Al-Harthy, M; Ohrbach, R; Michelotti, A; List, T

2016-02-01

Cross-cultural differences in pain sensitivity have been identified in pain-free subjects as well as in chronic pain patients. The aim was to assess the impact of culture on psychophysical measures using mechanical and electrical stimuli in patients with temporomandibular disorder (TMD) pain and pain-free matched controls in three cultures. This case-control study compared 122 female cases of chronic TMD pain (39 Saudis, 41 Swedes and 42 Italians) with equal numbers of age- and gender-matched TMD-free controls. Pressure pain threshold (PPT) and tolerance (PPTo) were measured over one hand and two masticatory muscles. Electrical perception threshold and electrical pain threshold (EPT) and tolerance (EPTo) were recorded between the thumb and index fingers. Italian females reported significantly lower PPT in the masseter muscle than other cultures (P < 0.001) and in the temporalis muscle than Saudis (P = 0.003). Swedes reported significantly higher PPT in the thenar muscle than other cultures (P = 0.017). Italians reported significantly lower PPTo in all muscles than Swedes (P ≤ 0.006) and in the masseter muscle than Saudis (P < 0.001). Italians reported significantly lower EPTo than other cultures (P = 0.01). Temporomandibular disorder cases, compared to TMD-free controls, reported lower PPT and PPTo in all the three muscles (P < 0.001). This study found cultural differences between groups in the PPT, PPTo and EPTo. Overall, Italian females reported the highest sensitivity to both mechanical and electrical stimulation, while Swedes reported the lowest sensitivity. Mechanical pain thresholds differed more across cultures than did electrical pain thresholds. Cultural factors may influence response to type of pain test. © 2015 John Wiley & Sons Ltd.

A preliminary study on how hypohydration affects pain perception.

PubMed

Bear, Tracey; Philipp, Michael; Hill, Stephen; Mündel, Toby

2016-05-01

Chronic pain is a prevalent health issue with one in five people suffering from some form of chronic pain, with loss of productivity and medical costs of chronic pain considerable. However, the treatment of pain can be difficult, as pain perception is complex and can be affected by factors other than tissue damage. This study investigated the effect of hypohydration (mild, voluntary dehydration from ∼24 h of limiting fluid intake, mimicking someone drinking less than usual) on a person's pain perception. Seventeen healthy males (age 27 ± 5 years) visited the laboratory on three occasions, once as a familiarization and then twice again while either euhydrated (urine specific gravity: 1.008 ± 0.005) or hypohydrated (urine specific gravity: 1.024 ± 0.003, and -1.4 ± 0.9% body mass). Each visit, they performed a cold pressor test, where their feet were placed in cold water (0-3 °C) for a maximum of 4 min. Measures of hydration status, pain sensitivity, pain threshold, and catastrophization were taken. We found that hypohydration predicted increased pain sensitivity (β = 0.43), trait pain catastrophizing, and baseline pain sensitivity (β = 0.37 and 0.47, respectively). These results are consistent with previous research, and suggest that a person's hydration status may be an important factor in their perception of acute pain. © 2016 Society for Psychophysiological Research.

Mechanisms of chronic pain - key considerations for appropriate physical therapy management.

PubMed

Courtney, Carol A; Fernández-de-Las-Peñas, César; Bond, Samantha

2017-07-01

In last decades, knowledge of nociceptive pain mechanisms has expanded rapidly. The use of quantitative sensory testing has provided evidence that peripheral and central sensitization mechanisms play a relevant role in localized and widespread chronic pain syndromes. In fact, almost any patient suffering with a chronic pain condition will demonstrate impairments in the central nervous system. In addition, it is accepted that pain is associated with different types of trigger factors including social, physiological, and psychological. This rational has provoked a change in the understanding of potential mechanisms of manual therapies, changing from a biomechanical/medical viewpoint, to a neurophysiological/nociceptive viewpoint. Therefore, interventions for patients with chronic pain should be applied based on current knowledge of nociceptive mechanisms since determining potential drivers of the sensitization process is critical for effective management. The current paper reviews mechanisms of chronic pain from a clinical and neurophysiological point of view and summarizes key messages for clinicians for proper management of individuals with chronic pain.

Napping reverses increased pain sensitivity due to sleep restriction.

PubMed

Faraut, Brice; Léger, Damien; Medkour, Terkia; Dubois, Alexandre; Bayon, Virginie; Chennaoui, Mounir; Perrot, Serge

2015-01-01

To investigate pain sensitivity after sleep restriction and the restorative effect of napping. A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed. Laboratory-based study. 11 healthy male volunteers. Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon. Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area. Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

The effect of acclimatization and ambient temperature on heat withdrawal threshold in rats.

PubMed

Vítková, J; Loučka, M; Boček, J; Vaculín, S

2015-01-01

Nociception in rats is frequently measured in terms of latency of withdrawal reaction to radiant heat (thermal nociceptive threshold). The aim of this study was to determine how much housing acclimatization and ambient temperature affect the results of thermal pain threshold testing. All experiments used adult male Wistar rats. Thermal pain thresholds were tested using the radiant heat withdrawal reaction at three different body sites: forepaws, hind paws and tail. Skin temperature was measured using an Infrared thermometer and ambient temperature was set at 18, 20, 24 or 26 °C. The results demonstrate that (1) thermal pain threshold was inversely related to both ambient and skin temperature; (2) housing acclimatization and repeated testing had no effect on nociceptive thresholds at any of the three body sites; (3) a resting, cranio-caudal distribution, of nociceptive sensitivity was observed; (4) hind paws and tail were more sensitive to changes of skin and ambient temperature than forepaws. These findings show the importance of recording laboratory conditions in experiments and their influence on results. © 2014 European Pain Federation - EFIC®

Diagnostic Accuracy of the Neck Tornado Test as a New Screening Test in Cervical Radiculopathy

PubMed Central

Park, Juyeon; Park, Woo Young; Hong, Seungbae; An, Jiwon; Koh, Jae Chul; Lee, Youn-Woo; Kim, Yong Chan; Choi, Jong Bum

2017-01-01

Background: The Spurling test, although a highly specific provocative test of the cervical spine in cervical radiculopathy (CR), has low to moderate sensitivity. Thus, we introduced the neck tornado test (NTT) to examine the neck and the cervical spine in CR. Objectives: The aim of this study was to introduce a new provocative test, the NTT, and compare the diagnostic accuracy with a widely accepted provocative test, the Spurling test. Design: Retrospective study. Methods: Medical records of 135 subjects with neck pain (CR, n = 67; without CR, n = 68) who had undergone cervical spine magnetic resonance imaging and been referred to the pain clinic between September 2014 and August 2015 were reviewed. Both the Spurling test and NTT were performed in all patients by expert examiners. Sensitivity, specificity, and accuracy were compared for both the Spurling test and the NTT. Results: The sensitivity of the Spurling test and the NTT was 55.22% and 85.07% (P < 0.0001); specificity, 98.53% and 86.76% (P = 0.0026); accuracy, 77.04% and 85.93% (P = 0.0423), respectively. Conclusions: The NTT is more sensitive with superior diagnostic accuracy for CR diagnosed by magnetic resonance imaging than the Spurling test. PMID:28824298

Athletic groin pain (part 1): a prospective anatomical diagnosis of 382 patients—clinical findings, MRI findings and patient-reported outcome measures at baseline

PubMed Central

Falvey, É C; King, E; Kinsella, S; Franklyn-Miller, A

2016-01-01

Background Athletic groin pain remains a common field-based team sports time-loss injury. There are few reports of non-surgically managed cohorts with athletic groin pain. Aim To describe clinical presentation/examination, MRI findings and patient-reported outcome (PRO) scores for an athletic groin pain cohort. Methods All patients had a history including demographics, injury duration, sport played and standardised clinical examination. All patients underwent MRI and PRO score to assess recovery. A clinical diagnosis of the injured anatomical structure was made based on these findings. Statistical assessment of the reliability of accepted standard investigations undertaken in making an anatomical diagnosis was performed. Result 382 consecutive athletic groin pain patients, all male, enrolled. Median time in pain at presentation was (IQR) 36 (16–75) weeks. Most (91%) played field-based ball-sports. Injury to the pubic aponeurosis (PA) 240 (62.8%) was the most common diagnosis. This was followed by injuries to the hip in 81 (21.2%) and adductors in 56 (14.7%) cases. The adductor squeeze test (90° hip flexion) was sensitive (85.4%) but not specific for the pubic aponeurosis and adductor pathology (negative likelihood ratio 1.95). Analysed in series, positive MRI findings and tenderness of the pubic aponeurosis had a 92.8% post-test probability. Conclusions In this largest cohort of patients with athletic groin pain combining clinical and MRI diagnostics there was a 63% prevalence of PA injury. The adductor squeeze test was sensitive for athletic groin pain, but not specific individual pathologies. MRI improved diagnostic post-test probability. No hernia or incipient hernia was diagnosed. Clinical trial registration number NCT02437942. PMID:26626272

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

PubMed

Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Paradoxical Pain Perception in Posttraumatic Stress Disorder: The Unique Role of Anxiety and Dissociation.

PubMed

Defrin, Ruth; Schreiber, Shaul; Ginzburg, Karni

2015-10-01

Posttraumatic stress disorder (PTSD) and chronic pain often co-occur and exacerbate each other. Elucidating the mechanism of this co-occurrence therefore has clinical importance. Previously, patients with PTSD with chronic pain were found to demonstrate a unique paradoxical pain profile: hyperresponsiveness together with hyposensitivity to pain. Our aim was to examine whether 2 seemingly paradoxical facets of PTSD (anxiety and dissociation) underlie this paradoxical profile. Patients with PTSD (n = 32) and healthy control individuals (n = 43) underwent psychophysical testing and completed questionnaires. Patients with PTSD had higher pain thresholds and higher pain ratings to suprathreshold stimuli than control individuals. Pain thresholds were positively associated with dissociation levels and negatively associated with anxiety sensitivity levels. Experimental pain ratings were positively associated with anxiety sensitivity and negatively related to dissociation levels. Chronic pain intensity was associated with anxiety, anxiety sensitivity, and pain catastrophizing. It appears that reduced conscious attention toward incoming stimuli, resulting from dissociation, causes delayed response in pain threshold measurement, whereas biases toward threatening stimuli and decreased inhibition, possibly caused by increased anxiety, are responsible for the intensification of experimental and chronic pain. The paradoxical facets of PTSD and their particular influences over pain perception seem to reinforce the coexistence of PTSD and chronic pain, and should be considered when treating traumatized individuals. This article provides new information regarding the underlying mechanism of the coexistence of PTSD and chronic pain. This knowledge could help to provide better management of PTSD and chronic pain among individuals in the aftermath of trauma. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Novel Signs and Their Clinical Utility in Diagnosing Complex Regional Pain Syndrome (CRPS): A Prospective Observational Cohort Study.

PubMed

Kuttikat, Anoop; Shaikh, Maliha; Oomatia, Amin; Parker, Richard; Shenker, Nicholas

2017-06-01

Delays in diagnosis occur with complex regional pain syndrome (CRPS). We define and prospectively demonstrate that novel bedside tests measuring body perception disruption can identify patients with CRPS postfracture. The objectives of our study were to define and validate 4 bedside tests, to identify the prevalence of positive tests in patients with CRPS and other chronic pain conditions, and to assess the clinical utility (sensitivity, specificity, positive predictive value, negative predictive value) for identifying CRPS within a Fracture cohort. This was a single UK teaching hospital prospective cohort study with 313 recruits from pain-free volunteers and patients with chronic pain conditions.Four novel tests were Finger Perception (FP), Hand Laterality identification (HL), Astereognosis (AS), and Body Scheme (BS) report. Five questionnaires (Brief Pain Inventory, Upper Extremity Functional Index, Lower Extremity Functional Index, Neglect-like Symptom Questionnaire, Hospital Anxiety and Depression Score) assessed the multidimensional pain experience. FP and BS were the best performing tests. Prospective monitoring of fracture patients showed that out of 7 fracture patients (total n=47) who had both finger misperception and abnormal BS report at initial testing, 3 developed persistent pain with 1 having a formal diagnosis of CRPS. Novel signs are reliable, easy to perform, and present in chronic pain patients. FP and BS have significant clinical utility in predicting persistent pain in a fracture group thereby allowing targeted early intervention.

Tactile allodynia in patients with lumbar radicular pain (sciatica).

PubMed

Defrin, Ruth; Devor, Marshall; Brill, Silviu

2014-12-01

We report a novel symptom in many patients with low back pain (LBP) that sheds new light on the underlying pain mechanism. By means of quantitative sensory testing, we compared patients with radicular LBP (sciatica), axial LBP (LBP without radiation into the leg), and healthy controls, searching for cutaneous allodynia in response to weak tactile and cooling stimuli on the leg and low back. Most patients with radicular pain (~60%) reported static and dynamic tactile allodynia, as well as cooling allodynia, on the leg, often extending into the foot. Some also reported allodynia on the low back. In axial LBP, allodynia was almost exclusively on the back. The degree of dynamic tactile allodynia correlated with the degree of background pain. The presence of allodynia suggests that the peripheral nerve generators of background leg and back pain have also induced central sensitization. The distal (foot) location of the allodynia in patients who have it indicates that the nociceptive drive that maintains the central sensitization arises paraspinally (ectopically) in injured ventral ramus afferents; this is not an instance of somatic referred pain. The presence of central sensitization also provides the first cogent account of shooting pain in sciatica as a wave of activity sweeping vectorially across the width of the sensitized dorsal horn. Finally, the results endorse leg allodynia as a pain biomarker in animal research on LBP, which is commonly used but has not been previously validated. In addition to informing the underlying mechanism of LBP, bedside mapping of allodynia might have practical implications for prognosis and treatment. How can you tell whether pain radiating into the leg in a patient with sciatica is neuropathic, ie, due to nerve injury? Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

PubMed Central

Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

2016-01-01

Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

Translation, cross-cultural adaptation, and validity of the Korean version of the pain sensitivity questionnaire in chronic pain patients.

PubMed

Kim, Ho-Joong; Ruscheweyh, Ruth; Yeo, Ji-Hyun; Cho, Hyeon-Guk; Yi, Je-Min; Chang, Bong-Soon; Lee, Choon-Ki; Yeom, Jin S

2014-11-01

The purpose of this study was to translate pain sensitivity questionnaires (PSQ) into the Korean language, perform a cross-cultural adaption of the PSQ, and validate the Korean version of PSQ in patients with degenerative spinal disease. The PSQ was translated forward and backward, cross-culturally adapted by 2 independent translators, and approved by an expert committee. The final Korean version of the PSQ was tested on 72 patients with degenerative spinal disease. Test-retest reliability was evaluated for 60 patients (83%) who completed the second assessment in an interval of 4 weeks. The mean PSQ-minor, PSQ-moderate, and PSQ-total (standard deviation [SD]) were 5.40 (2.02), 6.46 (1.98), and 5.93 (1.93), respectively. The PSQ-total, PSQ-minor, and PSQ-moderate of the Korean version showed very good internal consistencies determined by the Cronbach's α of 0.926, 0.869, and 0.877, respectively. For convergent validity, the PSQ scores of the Korean version showed significant correlations with pain catastrophizing scale (PCS) (r = 0.377, P = 0.002; r = 0.365, P = 0.003; r = 0.362, P = 0.003 for PSQ-total, PSQ-minor, and PSQ-moderate of the Korean version, respectively). For test-retest reliability, the intraclass correlation coefficients were 0.782 for PSQ-total, 0.752 for PSQ-minor, and 0.793 for PSQ-moderate. In conclusion, the validated Korean version of PSQ is a transculturally equivalent, reliable, and valid tool to assess individual pain sensitivity. © 2013 World Institute of Pain.

Effect of narcotic pain reliever on pulp tests in women.

PubMed

Kardelis, Anthony C; Meinberg, Trudy A; Sulte, Heather R; Gound, Tom G; Marx, David B; Reinhardt, Richard A

2002-07-01

The purpose of this study was to determine the effect of one dose of a common narcotic-based pain reliever (Vicodin) on a battery of oral sensitivity tests across time in women. Fifteen Caucasian women randomly were given an oral dose of 10 mg of hydrocodone/1000 mg of acetaminophen or placebo in a double-blind, cross-over design. At baseline (before drug) and after 2, 4, and 8 h each subject was evaluated for sensitivity thresholds with four tests around an experimental tooth: (a) electric pulp tester applied to exposed root; (b) electric pulp tester on adjacent mucosa; (c) increasing probe pressure (grams) on adjacent mucosa; and (d) decreasing cold probe (degrees C) on the exposed root. The outcomes of all tests were not statistically different between drug and placebo treatments at any time point (p > 0.05). These results suggest that a systemic dose of hydrocodone/acetaminophen has little impact on healthy pulp or mucosa sensitivity in women as measured by common diagnostic tests.

Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.

PubMed

Sutton, Blair C; Opp, Mark R

2014-03-01

Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization. Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved.

Effects of early human handling on the pain sensitivity of young lambs.

PubMed

Guesgen, Mirjam J; Beausoleil, Ngaio J; Stewart, Mairi

2013-01-01

Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Behavioral and endocrine consequences of placentophagia in male California mice (Peromyscus californicus).

PubMed

Perea-Rodriguez, Juan P; Zhao, Meng; Harris, Breanna N; Raqueno, Joel; Saltzman, Wendy

2018-05-01

Ingestion of placenta by mammalian mothers can lead to changes in pain sensitivity, hormone levels, and behavioral responses to newborns. In some biparental mammals, males, in addition to females, ingest placenta when their offspring are born. In the monogamous, biparental California mouse (Peromyscus californicus), males first become attracted to placenta when cohabitating with their pregnant mate, and virgin males administered placenta are less neophobic than males given oil vehicle. In this study, we investigated the effects of placentophagia on pain sensitivity, anxiety-like behavior, behavioral responses to pups, and circulating corticosterone levels of both breeding and nonbreeding male California mice. We orally administered either a conspecific placenta or oil vehicle to male mice from three reproductive conditions (first-time fathers, first-time expectant fathers, and virgin males) and tested their pain sensitivity 1 h later, as well as their exploratory behavior and paternal responsiveness in an open field 4 h post-treatment. We measured plasma corticosterone immediately after the open-field test. We found that placenta-treated males, independent of reproductive condition, traveled significantly longer distances in the open field than males treated with oil, indicative of lower anxiety. Additionally, fathers had shorter latencies to approach and to care for pups (i.e., huddling and licking pups), and spent more time engaging in these behaviors, than did age-matched expectant fathers and virgin males, independent of treatment. We found no effect on plasma corticosterone levels or pain sensitivity as a result of either treatment or reproductive condition. These findings indicate that placenta ingestion decreases anxiety-related behaviors in male California mice, but might not influence pain sensitivity, paternal responsiveness, or plasma corticosterone concentrations. Published by Elsevier Inc.

Evidence-Based Diagnosis and Treatment of the Painful Sacroiliac Joint

PubMed Central

Laslett, Mark

2008-01-01

Sacroiliac joint (SIJ) pain refers to the pain arising from the SIJ joint structures. SIJ dysfunction generally refers to aberrant position or movement of SIJ structures that may or may not result in pain. This paper aims to clarify the difference between these clinical concepts and present current available evidence regarding diagnosis and treatment of SIJ disorders. Tests for SIJ dysfunction generally have poor inter-examiner reliability. A reference standard for SIJ dysfunction is not readily available, so validity of the tests for this disorder is unknown. Tests that stress the SIJ in order to provoke familiar pain have acceptable inter-examiner reliability and have clinically useful validity against an acceptable reference standard. It is unknown if provocation tests can reliably identify extra-articular SIJ sources of pain. Three or more positive pain provocation SIJ tests have sensitivity and specificity of 91% and 78%, respectively. Specificity of three or more positive tests increases to 87% in patients whose symptoms cannot be made to move towards the spinal midline, i.e., centralize. In chronic back pain populations, patients who have three or more positive provocation SIJ tests and whose symptoms cannot be made to centralize have a probability of having SIJ pain of 77%, and in pregnant populations with back pain, a probability of 89%. This combination of test findings could be used in research to evaluate the efficacy of specific treatments for SIJ pain. Treatments most likely to be effective are specific lumbopelvic stabilization training and injections of corticosteroid into the intra-articular space. PMID:19119403

The Association Between Clinical Characteristics of Migraine and Brain GABA Levels: An Exploratory Study.

PubMed

Aguila, Maria-Eliza R; Rebbeck, Trudy; Leaver, Andrew M; Lagopoulos, Jim; Brennan, Patrick C; Hübscher, Markus; Refshauge, Kathryn M

2016-10-01

Migraine is prevalent and disabling yet is poorly understood. One way to better understand migraine is to examine its clinical characteristics and potential biomarkers such as gamma-aminobutyric acid (GABA). The primary objective of this study was to explore whether relevant disease characteristics of migraine are associated with brain GABA levels. Twenty adults fulfilling the established diagnostic criteria for migraine and 20 age- and gender-matched controls completed this cross-sectional study. Pain, central sensitization, negative emotional state, and perceived disability were measured using Short-form McGill Pain Questionnaire-2, Central Sensitization Inventory, Depression Anxiety Stress Scales-21, and Headache Impact Test-6, respectively. Secondary analysis of brain GABA levels of the same cohort measured using proton magnetic resonance spectroscopy was conducted. The migraine group had significantly higher scores than the control group on pain, central sensitization, and disability. Correlation analyses showed fair positive association between GABA levels and pain and central sensitization scores. No association was found between GABA levels and emotional state and disability. These findings are preliminary evidence supporting the use of questionnaires and GABA levels in characterizing migraine better and broadening the diagnostic process. These findings also strengthen the rationale for the role of GABA in migraine pathophysiology and corroborate the potential of GABA as a migraine biomarker. Higher pain and central sensitization scores were associated with increased brain GABA levels in individuals with migraine. These findings offer preliminary evidence for the usefulness of measuring pain and central sensitization in migraine and provide some support for the possible role of GABA in migraine pathophysiology and its potential as a diagnostic marker. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Pain during awake craniotomy for brain tumor resection. Incidence, causes, consequences and management.

PubMed

Fontaine, D; Almairac, F

2017-06-01

Awake craniotomy for brain tumor resection is usually well-tolerated and most of the patients are satisfied. However, in studies reporting the patients' postoperative perception of the awake craniotomy procedure, about half of them have experienced some degree of intraoperative pain. Pain was mild (intensity between 1 and 2 on the visual analogical score) short lasting in most cases, and did not challenge the procedure. Pain was reported as moderate in about 25% and exceptionally severe. We conducted a preliminary survey among French centers (n=9) routinely performing awake craniotomy. Neurosurgeons' opinions were concordant with patient's reports. Intraoperative pain exceptionally challenged the awake craniotomy procedure or led to changes in the resection strategy. For neurosurgeons, the most challenging causes of intraoperative pain were the patient's inadequate installation, the contact of surgical tools with pain-sensitive intracranial structures, especially the dura mater of the skull base, falx cerebri, and the leptomeninges of the lateral fissure and neighboring sulci. Strategies to deal with these causes included focusing the patient on the intraoperative functional tests to distract their attention away from the pain, and avoiding contacts with the pain-sensitive intracranial structures during the awake phase. Adequate preoperative patient information and preparation, trained anesthesiologists and application of recommendations for awake craniotomy procedures as well as adaptation of surgical technique to avoid contact with pain-sensitive intracranial structures are key factors to prevent intraoperative pain and ensure patient's postoperative satisfaction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Concurrent validity of different functional and neuroproteomic pain assessment methods in the rat osteoarthritis monosodium iodoacetate (MIA) model.

PubMed

Otis, Colombe; Gervais, Julie; Guillot, Martin; Gervais, Julie-Anne; Gauvin, Dominique; Péthel, Catherine; Authier, Simon; Dansereau, Marc-André; Sarret, Philippe; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Beaudry, Francis; Troncy, Eric

2016-06-23

Lack of validity in osteoarthritis pain models and assessment methods is suspected. Our goal was to 1) assess the repeatability and reproducibility of measurement and the influence of environment, and acclimatization, to different pain assessment outcomes in normal rats, and 2) test the concurrent validity of the most reliable methods in relation to the expression of different spinal neuropeptides in a chemical model of osteoarthritic pain. Repeatability and inter-rater reliability of reflexive nociceptive mechanical thresholds, spontaneous static weight-bearing, treadmill, rotarod, and operant place escape/avoidance paradigm (PEAP) were assessed by the intraclass correlation coefficient (ICC). The most reliable acclimatization protocol was determined by comparing coefficients of variation. In a pilot comparative study, the sensitivity and responsiveness to treatment of the most reliable methods were tested in the monosodium iodoacetate (MIA) model over 21 days. Two MIA (2 mg) groups (including one lidocaine treatment group) and one sham group (0.9 % saline) received an intra-articular (50 μL) injection. No effect of environment (observer, inverted circadian cycle, or exercise) was observed; all tested methods except mechanical sensitivity (ICC <0.3), offered good repeatability (ICC ≥0.7). The most reliable acclimatization protocol included five assessments over two weeks. MIA-related osteoarthritic change in pain was demonstrated with static weight-bearing, punctate tactile allodynia evaluation, treadmill exercise and operant PEAP, the latter being the most responsive to analgesic intra-articular lidocaine. Substance P and calcitonin gene-related peptide were higher in MIA groups compared to naive (adjusted P (adj-P) = 0.016) or sham-treated (adj-P = 0.029) rats. Repeated post-MIA lidocaine injection resulted in 34 times lower downregulation for spinal substance P compared to MIA alone (adj-P = 0.029), with a concomitant increase of 17 % in time spent on the PEAP dark side (indicative of increased comfort). This study of normal rats and rats with pain established the most reliable and sensitive pain assessment methods and an optimized acclimatization protocol. Operant PEAP testing was more responsive to lidocaine analgesia than other tests used, while neuropeptide spinal concentration is an objective quantification method attractive to support and validate different centralized pain functional assessment methods.

Quantitative sensory testing profiles in children, adolescents and young adults (6-20 years) with cerebral palsy: Hints for a neuropathic genesis of pain syndromes.

PubMed

Blankenburg, M; Junker, J; Hirschfeld, G; Michel, E; Aksu, F; Wager, J; Zernikow, B

2018-05-01

Many patients with cerebral palsy (CP) suffer chronic pain as one of the most limiting factors in their quality of life. In CP patients, pain mechanisms are not well understood, and pain therapy remains a challenge. Quantitative sensory testing (QST) might provide unique information about the functional status of the somatosensory system and therefore better guide pain treatment. To understand better the underlying pain mechanisms in pediatric CP patients, we aimed to assess clinical and pain parameters, as well as QST profiles, which were matched to the patients' cerebral imaging pathology. Thirty CP patients aged 6-20 years old (mean age 12 years) without intellectual impairment underwent standardized assessments of QST. Cerebral imaging was reassessed. QST results were compared to age- and sex-matched controls (multiple linear regression; Fisher's exact test; linear correlation analysis). CP patients were less sensitive to all mechanical and thermal stimuli than healthy controls but more sensitive to all mechanical pain stimuli (each p < 0.001). Fifty percent of CP patients showed a combination of mechanical hypoesthesia, thermal hypoesthesia and mechanical hyperalgesia; 67% of CP patients had periventricular leukomalacia (PVL), which was correlated with mechanic (r = 0.661; p < 0.001) and thermal (r = 0.624; p = 0.001) hypoesthesia. The combination of mechanical hypoesthesia, thermal hypoesthesia and mechanical hyperalgesia in our CP patients implicates lemniscal and extralemniscal neuron dysfunction in the thalamus region, likely due to PVL. We suspect that extralemniscal tracts are involved in the original of pain in our CP patients, as in adults. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

[Contemporary approach to evaluation of sensory disorders in polyneuropathy due to vibration].

PubMed

Nepershina, C P; Lagutina, G N; Kuzmina, L P; Skrypnik, O V; Ryabininal, S N; Lagutina, A P

2016-08-01

Recently, the studies search possibilities to visualize and objectify sensory disorders in polyneuropathy caused by vibration. Special attention is paid on studies of injuried structures responsible for temperature and pain sensitivity. Examination covered 92 patients with vibration disease, aged 34 to 73 years. Methods used are: pallesthesiometry, quantitative sensory tests, questionnaires and s 'cales of pain (visual analog scale (VAS) of pain, Pain-Detect, MPQ DN-, HADS). Correlation was found between.temperature, pain thresholds and VAS and pallesthesiometry parameters. The obtained results analysis indicates formation distal polyneuropathy syndrome of upper limbs with concomitant pain during vibration disease.

Neural and psychosocial mechanisms of pain sensitivity in fibromyalgia.

PubMed

English, Brian

2014-06-01

Fibromyalgia is a chronic musculoskeletal pain disorder that affects an estimated 5 million adults in the U.S. The hallmark is burning, searing, tingling, shooting, stabbing, deep aching, or sharp pain. Fibromyalgia is generally considered to be a "central sensitivity syndrome" where central sensitization is regarded as the cause of pain in its own right. Nonetheless, the case continues to be made that all central and spatially distributed peripheral components of fibromyalgia pain would fade if the peripheral generators could be silenced. Although neural mechanisms are clearly important in pain sensitivity, cognitive and social mechanisms also need to be considered. The aim of this review is to examine four mechanisms responsible for heightened pain sensitivity in fibromyalgia: peripheral sensitization, central sensitization, cognitive-emotional sensitization, and interpersonal sensitization. The purpose of framing the review in terms of pain sensitivity in fibromyalgia is to highlight that different mechanisms of sensitization are appropriately regarded as intervening variables when it comes to understanding individual differences in the experience of pain. The paper concludes by considering the implications of the findings of the review for explanations of fibromyalgia pain by nurses working in multidisciplinary teams. The trend appears to be able to explain the cause of fibromyalgia pain in terms of sensitization per se. The recommended alternative is to explain fibromyalgia pain in terms of changes in pain sensitivity and the role of underlying neural and psychosocial mechanisms. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Napping Reverses Increased Pain Sensitivity Due to Sleep Restriction

PubMed Central

Faraut, Brice; Léger, Damien; Medkour, Terkia; Dubois, Alexandre; Bayon, Virginie; Chennaoui, Mounir; Perrot, Serge

2015-01-01

Study Objective To investigate pain sensitivity after sleep restriction and the restorative effect of napping. Design A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed. Setting Laboratory-based study. Participants 11 healthy male volunteers. Interventions Volunteers attended two three-day sessions: “sleep restriction” alone and “sleep restriction and nap”. Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the “sleep restriction and nap” session, volunteers took two 30-minute naps, one in the morning and one in the afternoon. Measurements and Results Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area. Conclusions Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status. PMID:25723495

Shoulder pain in primary care: diagnostic accuracy of clinical examination tests for non-traumatic acromioclavicular joint pain

PubMed Central

2013-01-01

Background Despite numerous methodological flaws in previous study designs and the lack of validation in primary care populations, clinical tests for identifying acromioclavicular joint (ACJ) pain are widely utilised without concern for such issues. The aim of this study was to estimate the diagnostic accuracy of traditional ACJ tests and to compare their accuracy with other clinical examination features for identifying a predominant ACJ pain source in a primary care cohort. Methods Consecutive patients with shoulder pain were recruited prospectively from primary health care clinics. Following a standardised clinical examination and diagnostic injection into the subacromial bursa, all participants received a fluoroscopically guided diagnostic block of 1% lidocaine hydrochloride (XylocaineTM) into the ACJ. Diagnostic accuracy statistics including sensitivity, specificity, predictive values, positive and negative likelihood ratios (LR+ and LR-) were calculated for traditional ACJ tests (Active Compression/O’Brien’s test, cross-body adduction, localised ACJ tenderness and Hawkins-Kennedy test), and for individual and combinations of clinical examination variables that were associated with a positive anaesthetic response (PAR) (P≤0.05) defined as 80% or more reduction in post-injection pain intensity during provocative clinical tests. Results Twenty two of 153 participants (14%) reported an 80% PAR. None of the traditional ACJ tests were associated with an 80% PAR (P<0.05) and combinations of traditional tests were not able to discriminate between a PAR and a negative anaesthetic response (AUC 0.507; 95% CI: 0.366, 0.647; P>0.05). Five clinical examination variables (repetitive mechanism of pain onset, no referred pain below the elbow, thickened or swollen ACJ, no symptom provocation during passive glenohumeral abduction and external rotation) were associated with an 80% PAR (P<0.05) and demonstrated an ability to accurately discriminate between an PAR and NAR (AUC 0.791; 95% CI 0.702, 0.880; P<0.001). Less than two positive clinical features resulted in 96% sensitivity (95% CI 0.78, 0.99) and a LR- 0.09 (95% CI 0.02, 0.41) and four positive clinical features resulted in 95% specificity (95% CI 0.90, 0.98) and a LR+ of 4.98 (95% CI 1.69, 13.84). Conclusions In this cohort of primary care patients with predominantly subacute or chronic ACJ pain of non-traumatic onset, traditional ACJ tests were of limited diagnostic value. Combinations of other history and physical examination findings were able to more accurately identify injection-confirmed ACJ pain in this cohort. PMID:23634871

Relationship Between ABCB1 Polymorphisms and Cold Pain Sensitivity Among Healthy Opioid-naive Malay Males.

PubMed

Zahari, Zalina; Lee, Chee Siong; Ibrahim, Muslih Abdulkarim; Musa, Nurfadhlina; Mohd Yasin, Mohd Azhar; Lee, Yeong Yeh; Tan, Soo Choon; Mohamad, Nasir; Ismail, Rusli

2017-09-01

Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males. Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction. A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype. The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males. © 2016 World Institute of Pain.

Physical examination for lumbar radiculopathy due to disc herniation in patients with low-back pain.

PubMed

van der Windt, Daniëlle Awm; Simons, Emmanuel; Riphagen, Ingrid I; Ammendolia, Carlo; Verhagen, Arianne P; Laslett, Mark; Devillé, Walter; Deyo, Rick A; Bouter, Lex M; de Vet, Henrica Cw; Aertgeerts, Bert

2010-02-17

Low-back pain with leg pain (sciatica) may be caused by a herniated intervertebral disc exerting pressure on the nerve root. Most patients will respond to conservative treatment, but in carefully selected patients, surgical discectomy may provide faster relief of symptoms. Primary care clinicians use patient history and physical examination to evaluate the likelihood of disc herniation and select patients for further imaging and possible surgery. (1) To assess the performance of tests performed during physical examination (alone or in combination) to identify radiculopathy due to lower lumbar disc herniation in patients with low-back pain and sciatica;(2) To assess the influence of sources of heterogeneity on diagnostic performance. We searched electronic databases for primary studies: PubMed (includes MEDLINE), EMBASE, and CINAHL, and (systematic) reviews: PubMed and Medion (all from earliest until 30 April 2008), and checked references of retrieved articles. We considered studies if they compared the results of tests performed during physical examination on patients with back pain with those of diagnostic imaging (MRI, CT, myelography) or findings at surgery. Two review authors assessed the quality of each publication with the QUADAS tool, and extracted details on patient and study design characteristics, index tests and reference standard, and the diagnostic two-by-two table. We presented information on sensitivities and specificities with 95% confidence intervals (95% CI) for all aspects of physical examination. Pooled estimates of sensitivity and specificity were computed for subsets of studies showing sufficient clinical and statistical homogeneity. We included 16 cohort studies (median N = 126, range 71 to 2504) and three case control studies (38 to100 cases). Only one study was carried out in a primary care population. When used in isolation, diagnostic performance of most physical tests (scoliosis, paresis or muscle weakness, muscle wasting, impaired reflexes, sensory deficits) was poor. Some tests (forward flexion, hyper-extension test, and slump test) performed slightly better, but the number of studies was small. In the one primary care study, most tests showed higher specificity and lower sensitivity compared to other settings.Most studies assessed the Straight Leg Raising (SLR) test. In surgical populations, characterized by a high prevalence of disc herniation (58% to 98%), the SLR showed high sensitivity (pooled estimate 0.92, 95% CI: 0.87 to 0.95) with widely varying specificity (0.10 to 1.00, pooled estimate 0.28, 95% CI: 0.18 to 0.40). Results of studies using imaging showed more heterogeneity and poorer sensitivity. The crossed SLR showed high specificity (pooled estimate 0.90, 95% CI: 0.85 to 0.94) with consistently low sensitivity (pooled estimate 0.28, 95% CI: 0.22 to 0.35).Combining positive test results increased the specificity of physical tests, but few studies presented data on test combinations. When used in isolation, current evidence indicates poor diagnostic performance of most physical tests used to identify lumbar disc herniation. However, most findings arise from surgical populations and may not apply to primary care or non-selected populations. Better performance may be obtained when tests are combined.

Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

PubMed

Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

2016-01-01

One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

Responsiveness of clinical tests for people with neck pain.

PubMed

Jørgensen, René; Ris, Inge; Juhl, Carsten; Falla, Deborah; Juul-Kristensen, Birgit

2017-12-28

Responsiveness of a clinical test is highly relevant in order to evaluate the effect of a given intervention. However, the responsiveness of clinical tests for people with neck pain has not been adequately evaluated. The objective of the present study was to examine the responsiveness of four clinical tests which are low cost and easy to perform in a clinical setting, including the craniocervical flexion test, cervical active range of movement, test for the cervical extensors and pressure pain threshold testing. This study is a secondary analysis of data collected in a previously published randomised controlled trial. Participants were randomized to either physical training, exercises and pain education combined or pain education only. Participants were tested on the clinical tests at baseline and at 4-month follow-up. An anchor-based approach using Receiver Operator Characteristics (ROC) curves was used to evaluate responsiveness of the clinical tests. The Neck Disability Index was used to discriminate between those who had improved and those who were unchanged at the 4-month follow-up. Minimum Clinically Important Difference (MCID), together with sensitivity, specificity, positive and negative predictive values, in addition to positive and negative likelihood ratios were calculated. In total, 164 participants completed the 4 month follow up. One-hundred forty four participants were classified as unchanged whereas 20 patients were considered to be improved. Twenty-six participants didn't complete all of the clinical tests, leaving a total of 138 to be included for analyses. Area Under Curve (AUC) ranged from 0.50-0.62 for the clinical tests, and were all below an acceptable level. MCID was generally large, and the corresponding sensitivity and specificity was low with sensitivity ranging from 20 to 60%, and specificity from 54 to 86%. LR+ (0.8-2.07) and LR- (0.7-1.1) showed low diagnostic value for all variables, with PPV ranging from 12.1 to 26.1 and NPV ranging from 84.7 to 89.2. Responsiveness of the included clinical tests was generally low when using change in NDI score as the anchor from baseline to the 4-month follow up. Further investigations of responsiveness are warranted, possibly using other anchors, which to a higher degree resemble similar dimensions as the clinical tests.

Sleep Fragmentation Exacerbates Mechanical Hypersensitivity and Alters Subsequent Sleep-Wake Behavior in a Mouse Model of Musculoskeletal Sensitization

PubMed Central

Sutton, Blair C.; Opp, Mark R.

2014-01-01

Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization. Conclusions: Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved. Citation: Sutton BC; Opp MR. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization. SLEEP 2014;37(3):515-524. PMID:24587574

An observational study of the impact of genetic testing for pain perception in the clinical management of chronic non-cancer pain.

PubMed

Sharma, Maneesh; Kantorovich, Svetlana; Lee, Chee; Anand, Natasha; Blanchard, John; Fung, Eric T; Meshkin, Brian; Brenton, Ashley; Richeimer, Steven

2017-06-01

Pain levels are a key metric in clinical care. However, the assessment of pain is limited to basic questionnaires and physician interpretation, which yield subjective data. Genetic markers of pain sensitivity, such as single nucleotide polymorphisms in the catechol-O-methyltransferase gene, have been shown to be associated with pain perception and have been used to provide objective information about a patient's pain. The goal of this study was to determine if physician treatment adjustments based on genetic tests of pain perception resulted in improved outcomes for patients. A prospective, longitudinal study was conducted with 134 chronic non-cancer pain patients genotyped for pain perception-related catechol-O-methyltransferase haplotypes. Physicians were provided with patients' results and asked to document 1) their assessment of benefit of the genetic test; 2) treatment changes made based on the genetic test; and 3) patient clinical responses to changes implemented. Based on genetic testing results, physicians adjusted treatment plans for 40% of patients. When medication changes were made based on genetic testing results, 72% of patients showed improvement in clinical status. When non-pharmacological actions were performed, 69% of physicians felt their patients' clinical status improved. Moreover, physicians believed the genetic test results were consistent with patient pain levels in 85% of cases. These results demonstrate that providing personalized medicine with genetic information related to pain perception affected physician clinical decision-making for a substantial proportion of patients in this study, and that the availability and utilization of this information was a contributing factor in clinical improvement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Food sensitivity in reflux esophagitis.

PubMed

Price, S F; Smithson, K W; Castell, D O

1978-08-01

We examined 66 patients with pain of possible esophageal origin for sensitivity to intraesophageal infusions of coffee, orange juice, spicy tomato drink, or HCl of varying concentrations as an addendum to their acid infusion (Bernstein) tests. Compared to Berstein-negative subjects, acid-sensitive patients were sensitive to infusion of coffee (P less than 0.01), orange juice (P less than 0.001), and tomato drink (P less than 0.001). Patients were largely insensitive to HCl solutions with a titratable acidity of 1 mEq per liter or less, less than the least acidic food solution tested. However, Berstein-positive patients were still highly sensitive to infusions of coffee, orange juice, and tomato drink adjusted to pH 7 (P less than 0.001). Patients were unable to differentiate symptoms caused by acid or food infusions, and solutions did not differ in the duration of infusion needed either to cause symptoms or to relieve them by saline. We conclude that the pain of esophagitis is nonspecific and can be precipitated by variety of seemingly unrelated substances.

Neuroimaging, Pain Sensitivity, and Neuropsychological Functioning in School-Age Neonatal Extracorporeal Membrane Oxygenation Survivors Exposed to Opioids and Sedatives.

PubMed

van den Bosch, Gerbrich E; IJsselstijn, Hanneke; van der Lugt, Aad; Tibboel, Dick; van Dijk, Monique; White, Tonya

2015-09-01

Animal studies found negative long-term effects of exposure to sedatives and opioids in early life, especially when administered in the absence of pain. Around the world, children who require extracorporeal membrane oxygenation receive opioids and sedatives for extended periods, generally in the absence of major pain as extracorporeal membrane oxygenation cannulation is considered minor surgery. Therefore, our objective was to determine the long-term effects of extracorporeal membrane oxygenation treatment with respect to pain sensitivity, brain functioning during pain, brain morphology, and neuropsychological functioning in humans. Prospective follow-up study. Level III university hospital. Thirty-six extracorporeal membrane oxygenation survivors (8.1-15.5 yr) and 64 healthy controls (8.2-15.3 yr). We measured detection and pain thresholds, brain activity during pain (functional MRI), brain morphology (high-resolution structural MRI), and neuropsychological functioning and collected information regarding the subject's experience of chronic pain. We found a significant difference in the detection threshold for cold measured in a reaction time-dependent fashion (extracorporeal membrane oxygenation group, 29.9°C [SD, 1.4]; control group, 30.6°C [SD, 0.8]; p < 0.01), but no differences in other modalities or in pain sensitivity between groups. Furthermore, no differences in brain activation during pain, brain morphology, or in the occurrence of chronic pain were observed. However, extracorporeal membrane oxygenation survivors performed significantly worse on a verbal memory test compared with controls (p = 0.001). While the most critically ill newborns receive extracorporeal membrane oxygenation and, relatedly, large doses of opioids and sedatives for extended periods, global measures of pain sensitivity and neurobiological and neuropsychological development appear to have minor long-term consequences. Possible memory deficits in extracorporeal membrane oxygenation survivors require additional study, but neonatal extracorporeal membrane oxygenation treatment and associated exposure to opioids and sedatives seem less harmful to humans than expected from animal studies.

An evaluation of the hemiplegic subject based on the Bobath approach. Part III. A validation study.

PubMed

Arsenault, A B; Dutil, E; Lambert, J; Corriveau, H; Guarna, F; Drouin, G

1988-01-01

Sixty-two hemiplegic subjects were treated with the Bobath approach for a period of three months. During this time they were evaluated on three occasions. The testing battery consisted of a Bobath evaluation, the Brunnstrom scale, the Fugl-Meyer test, the Upper Extremity Functional Test (UEFT) and the Present Pain Intensity (PPI) of the McGill pain questionnaire. A Friedman analysis of variance showed that, except for pain, all the protocols used disclosed significant progress (p less than 0.001) over time in terms of motor recovery. Except for pain, the results of the Bobath evaluation were significantly correlated (Spearman's Rho, p less than 0.001) with the results of the other testing procedures. It is concluded that the new Bobath evaluation proposed in a previous paper is as sensitive in depicting progress in motor recovery over time as are the other testing procedures used. Furthermore, this new evaluation seems to be measuring similar properties to the other tests. However, pain (PPI) appears not to be an important dependent variable.

Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses.

PubMed

Matre, Dagfinn; Hu, Li; Viken, Leif A; Hjelle, Ingri B; Wigemyr, Monica; Knardahl, Stein; Sand, Trond; Nilsen, Kristian Bernhard

2015-10-01

Sleep restriction (SR) has been hypothesized to sensitize the pain system. The current study determined whether experimental sleep restriction had an effect on experimentally induced pain and pain-elicited electroencephalographic (EEG) responses. A paired crossover study. Pain testing was performed after 2 nights of 50% SR and after 2 nights with habitual sleep (HS). Laboratory experiment at research center. Self-reported healthy volunteers (n = 21, age range: 18-31 y). Brief high-density electrical stimuli to the forearm skin produced pinprick-like pain. Subjective pain ratings increased after SR, but only in response to the highest stimulus intensity (P = 0.018). SR increased the magnitude of the pain-elicited EEG response analyzed in the time-frequency domain (P = 0.021). Habituation across blocks did not differ between HS and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039). Pressure pain threshold of the trapezius muscle region also decreased after SR (P = 0.017). Sleep restriction (SR) increased the sensitivity to pressure pain and to electrically induced pain of moderate, but not low, intensity. The increased electrical pain could not be explained by a difference in habituation. Increased response magnitude is possibly related to reduced processing within the somatosensory cortex after partial SR. © 2015 Associated Professional Sleep Societies, LLC.

Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study

PubMed Central

Sturgeon, John A.; Johnson, Kevin A.

2017-01-01

Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period). All participants underwent a baseline round of several quantitative sensory testing (QST) tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain. PMID:28348505

Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study.

PubMed

Taub, Chloe J; Sturgeon, John A; Johnson, Kevin A; Mackey, Sean C; Darnall, Beth D

2017-01-01

Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period). All participants underwent a baseline round of several quantitative sensory testing (QST) tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain.

Effect of intrathecal baclofen on evoked pain perception: an evoked potentials and quantitative thermal testing study.

PubMed

Kumru, H; Kofler, M; Flores, M C; Portell, E; Robles, V; Leon, N; Vidal, J

2013-08-01

Somatic antinociceptive effects of baclofen have been demonstrated in animal models. We hypothesized that if enhanced thermal or pain sensitivity is produced by loss of gamma-aminobutyric acid (GABA)-ergic tone in the central nervous system, spinal administration of GABA agonists might be predicted to be effective in thermal and/or pain perception changes and pain-related evoked potentials in candidates for intrathecal baclofen (ITB) treatment. Eleven patients with severe spinal cord injury (SCI) who suffered from severe spasticity were evaluated during a 50-μg ITB bolus test. Warm and heat pain thresholds, evoked heat pain perception, and contact heat-evoked potentials (CHEPs) were determined above SCI level from the right and left sides. Nine age- and gender-matched healthy volunteers undergoing repeat testing without any placebo injection served as control group. In patients, heat pain perception threshold increased, and evoked pain perception and amplitude of CHEPs decreased significantly after ITB bolus application in comparison with baseline (p < 0.005), with no change in warm perception threshold. In controls, no significant changes were observed in repeat testing over time. Our findings indicate that ITB modulates heat pain perception threshold, evoked heat pain perception and heat pain-related evoked potentials without inducing warm perception threshold changes in SCI patients. This phenomenon should be taken into account in the clinical evaluation and management of pain in patients receiving baclofen. © 2012 European Federation of International Association for the Study of Pain Chapters.

Evoked Pressure Pain Sensitivity Is Associated with Differential Analgesic Response to Verum and Sham Acupuncture in Fibromyalgia.

PubMed

Zucker, Noah A; Tsodikov, Alex; Mist, Scott D; Cina, Stephen; Napadow, Vitaly; Harris, Richard E

2017-08-01

Fibromyalgia is a chronic pain condition with few effective treatments. Many fibromyalgia patients seek acupuncture for analgesia; however, its efficacy is limited and not fully understood. This may be due to heterogeneous pathologies among participants in acupuncture clinical trials. We hypothesized that pressure pain tenderness would differentially classify treatment response to verum and sham acupuncture in fibromyalgia patients. Baseline pressure pain sensitivity at the thumbnail at baseline was used in linear mixed models as a modifier of differential treatment response to sham versus verum acupuncture. Similarly, needle-induced sensation was also analyzed to determine its differential effect of treatment on clinical pain. A cohort of 114 fibromyalgia patients received baseline pressure pain testing and were randomized to either verum (N = 59) or sham (N = 55) acupuncture. Participants received treatments from once a week to three times a week, increasing in three-week blocks for a total of 18 treatments. Clinical pain was measured on a 101-point visual analog scale, and needle sensation was measured by questionnaire throughout the trial. Participants who had higher pain pressure thresholds had greater reduction in clinical pain following verum acupuncture while participants who had lower pain pressure thresholds showed better analgesic response to sham acupuncture. Moreover, patients with lower pressure pain thresholds had exacerbated clinical pain following verum acupuncture. Similar relationships were observed for sensitivity to acupuncture needling. These findings suggest that acupuncture efficacy in fibromyalgia may be underestimated and a more personalized treatment for fibromyalgia may also be possible. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Dynamic Pain Phenotypes are Associated with Spinal Cord Stimulation-Induced Reduction in Pain: A Repeated Measures Observational Pilot Study.

PubMed

Campbell, Claudia M; Buenaver, Luis F; Raja, Srinivasa N; Kiley, Kasey B; Swedberg, Lauren J; Wacnik, Paul W; Cohen, Steven P; Erdek, Michael A; Williams, Kayode A; Christo, Paul J

2015-07-01

Spinal cord stimulation (SCS) has become a widely used treatment option for a variety of pain conditions. Substantial variability exists in the degree of benefit obtained from SCS and patient selection is a topic of expanding interest and importance. However, few studies have examined the potential benefits of dynamic quantitative sensory testing (QST) to develop objective measures of SCS outcomes or as a predictive tool to help patient selection. Psychological characteristics have been shown to play an important role in shaping individual differences in the pain experience and may aid in predicting responses to SCS. Static laboratory pain-induction measures have also been examined in their capacity for predicting SCS outcomes. The current study evaluated clinical, psychological and laboratory pain measures at baseline, during trial SCS lead placement, as well as 1 month and 3 months following permanent SCS implantation in chronic pain patients who received SCS treatment. Several QST measures were conducted, with specific focus on examination of dynamic models (central sensitization and conditioned pain modulation [CPM]) and their association with pain outcomes 3 months post SCS implantation. Results suggest few changes in QST over time. However, central sensitization and CPM at baseline were significantly associated with clinical pain at 3 months following SCS implantation, controlling for psycho/behavioral factors and pain at baseline. Specifically, enhanced central sensitization and reduced CPM were associated with less self-reported pain 3 months following SCS implantation. These findings suggest a potentially important role for dynamic pain assessment in individuals undergoing SCS, and hint at potential mechanisms through which SCS may impart its benefit. Wiley Periodicals, Inc.

Centralization as a predictor of provocation discography results in chronic low back pain, and the influence of disability and distress on diagnostic power.

PubMed

Laslett, Mark; Oberg, Birgitta; Aprill, Charles N; McDonald, Barry

2005-01-01

The "centralization phenomenon" (CP) is the progressive retreat of referred pain towards the spinal midline in response to repeated movement testing (a McKenzie evaluation). A previous study suggested that it may have utility in the clinical diagnosis of discogenic pain and may assist patient selection for discography and specific treatments for disc pain. Estimation of the diagnostic predictive power of centralization and the influence of disability and patient distress on diagnostic performance, using provocation discography as a criterion standard for diagnosis, in chronic low back pain patients. This study was a prospective, blinded, concurrent, reference standard-related validity design carried out in a private radiology clinic specializing in diagnosis of chronic spinal pain. Consecutive patients with persistent low back pain were referred to the study clinic by orthopedists and other medical specialists for interventional radiological diagnostic procedures. Patients were typically disabled and displayed high levels of psychosocial distress. The sample included patients with previous lumbar surgery, and most had unsuccessful conservative therapies previously. results of provocation discography. The CP. Psychometric evaluation: Roland-Morris, Zung, Modified Somatic Perception questionnaires, Distress Risk Assessment Method, and 100-mm visual analog scales for pain intensity. Patients received a single physical therapy examination, followed by lumbar provocation discography. Sensitivity, specificity, and likelihood ratios of the CP were estimated in the group as a whole and in subgroups defined by psychometric measures. A total of 107 patients received the clinical examination and discography at two or more levels and post-discography computed tomography. Thirty-eight could not tolerate a full physical examination and were excluded from the main analysis. Disability and pain intensity ratings were high, and distress was common. Sensitivity, specificity, and positive likelihood ratios for centralization observed during repeated movement testing for pain distribution and intensity changes were 40%, 94%, and 6.9 respectively. In the presence of severe disability, sensitivity, specificity, and positive likelihood ratios were 46%, 80%, 3.2 and for distress, 45%, 89%, 4.1. In the subgroups with moderate, minimal, or no disability, sensitivity and specificity were 37%, 100% and for no or minimal distress 35%, 100%. Centralization is highly specific to positive discography but specificity is reduced in the presence of severe disability or psychosocial distress.

Anxiety sensitivity, fear of pain and pain-related disability in children and adolescents with chronic pain

PubMed Central

Martin, Andrea L; McGrath, Patricia A; Brown, Stephen C; Katz, Joel

2007-01-01

BACKGROUND: Converging lines of evidence suggest that anxiety sensitivity and fear of pain may be important vulnerability factors in the development of avoidance behaviours and disability in adults with chronic pain. However, these factors have not been evaluated in children with chronic pain. OBJECTIVES: To examine the relationships among anxiety sensitivity, fear of pain and pain-related disability in children and adolescents with chronic pain. METHODS: An interview and five questionnaires (Childhood Anxiety Sensitivity Index, Pain Anxiety Symptoms Scale, Functional Disability Inventory, Multidimensional Anxiety Scale for Children, and Reynolds Child or Adolescent Depression Scale) were administered to 21 children and adolescents eight to 17 years of age (mean ± SD 14.24±2.21 years) who continued to experience pain an average of three years after discharge from a specialized pain clinic for children. RESULTS: Anxiety sensitivity accounted for 38.6% of the variance in fear of pain (F[1,20]=11.30; P=0.003) and fear of pain accounted for 39.9% of the variance in pain-related disability (F[1,20]=11.95; P=0.003), but anxiety sensitivity was not significantly related to pain disability (R2=0.09; P>0.05). CONCLUSIONS: These findings indicate that children with high levels of anxiety sensitivity had a higher fear of pain, which, in turn, was linked to increased pain disability. The results of this study suggest that anxiety sensitivity and fear of pain may play important and distinct roles in the processes that maintain chronic pain and pain-related disability in children. PMID:18080045

Diagnostic accuracy: sensitivity and specificity of the ScreenAssist Lumbar Questionnaire in comparison with primary care provider tests and measures of low back pain: a pilot study

PubMed Central

Cunningham, Shala

2013-01-01

Objective: The purpose of this study was to estimate the diagnostic accuracy of the ScreenAssist Lumbar Questionnaire (SALQ) to determine the presence of non-musculoskeletal pain or emergent musculoskeletal pain, in terms of its sensitivity and specificity, when compared with the assessment and diagnosis made by primary care providers. Methods: Subjects were patients presenting to a primary care physician’s office with the main complaint of low back pain. SALQ data were collected within 24 hours of the appointment. A 2-month post-visit chart review was performed in order to compare scores and recommendations made by the questionnaire with the assessment and diagnosis made by the physician. Results: The SALQ demonstrated a sensitivity of 100% (95% CI = 0.445–1.0) and specificity of 92% (95% CI = 0.831–0.920). The negative likelihood ratio was 0.11 (95% CI = 0.01–1.54) and the positive likelihood ratio was 9.36 (95% CI = 2.78–32). If the SALQ was positive, the post-test probability was 0.60. If the SALQ was negative, the post-test probability was 0.017. Discussion: Results from this study suggest that the SALQ can be used as an adjunct to the subjective history taking in a physical therapy evaluation to assist in the recognition of non-musculoskeletal or emergent musculoskeletal conditions requiring referral. PMID:24421613

Pain referral and regional deep tissue hyperalgesia in experimental human hip pain models.

PubMed

Izumi, Masashi; Petersen, Kristian Kjær; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

2014-04-01

Hip disorder patients typically present with extensive pain referral and hyperalgesia. To better understand underlying mechanisms, an experimental hip pain model was established in which pain referrals and hyperalgesia could be studied under standardized conditions. In 16 healthy subjects, pain was induced by hypertonic saline injection into the gluteus medius tendon (GMT), adductor longus tendon (ALT), or gluteus medius muscle (GMM). Isotonic saline was injected contralaterally as control. Pain intensity was assessed on a visual analogue scale (VAS), and subjects mapped the pain distribution. Before, during, and after injections, passive hip joint pain provocation tests were completed, together with quantitative sensory testing as follows: pressure pain thresholds (PPTs), cuff algometry pain thresholds (cuff PPTs), cutaneous pin-prick sensitivity, and thermal pain thresholds. Hypertonic saline injected into the GMT resulted in higher VAS scores than hypertonic injections into the ALT and GMM (P<.05). Referred pain areas spread to larger parts of the leg after GMT and GMM injections compared with more regionalized pain pattern after ALT injections (P<.05). PPTs at the injection site were decreased after hypertonic saline injections into GMT and GMM compared with baseline, ALT injections, and isotonic saline. Cuff PPTs from the thigh were decreased after hypertonic saline injections into the ALT compared with baseline, GMT injections, and isotonic saline (P<.05). More subjects had positive joint pain provocation tests after hypertonic compared with isotonic saline injections (P<.05), indicating that this provocation test also assessed hyperalgesia in extra-articular soft tissues. The experimental models may open for better understanding of pain mechanisms associated with painful hip disorders. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Characterization of peripheral and central sensitization after dorsal root ganglion intervention in patients with unilateral lumbosacral radicular pain: a prospective pilot study.

PubMed

Mehta, V; Snidvongs, S; Ghai, B; Langford, R; Wodehouse, T

2017-06-01

Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG. Questionnaires and QST scores were measured before the DRG blocks and at 1 week and 3 months after their procedure. Those who received PRF also answered questionnaires and underwent QST measurements at 1 week and 3 months after their procedure. There was a significant increase in pressure pain threshold scores after DRG blocks. A reduced conditioned pain modulation response was seen before DRG, which increased after the procedure. Ten out of 23 patients underwent PRF to the DRG, and an increase in pressure pain threshold scores after PRF was observed. The conditioned pain modulation response was maintained in this group and increased after PRF. The study demonstrates that patients with unilateral radicular low back pain who receive dorsal root ganglion interventions show changes in pressure pain thresholds and conditioned pain modulation that are consistent with a 'normalization' of peripheral and central sensitization. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Evidence of Nervous System Sensitization in Commonly Presenting and Persistent Painful Tendinopathies: A Systematic Review.

PubMed

Plinsinga, Melanie L; Brink, Michel S; Vicenzino, Bill; van Wilgen, C Paul

2015-11-01

Study Design Systematic review. Objectives To elucidate if there is sensitization of the nervous system in those with persistent rotator cuff (shoulder), lateral elbow, patellar, and Achilles tendinopathies. Background Tendinopathy can be difficult to treat, and persistent intractable pain and dysfunction are frequent. It is hypothesized that induction or maintenance of persistent pain in tendinopathy may be, at least in part, based on changes in the nervous system. Methods The PRISMA guidelines were followed. Relevant articles were identified through a computerized search in Embase, PubMed, and Web of Science, followed by a manual search of reference lists of retained articles. To be eligible, studies had to include quantitative sensory testing and evaluate individuals diagnosed with a persistent tendinopathy of the rotator cuff (shoulder), lateral elbow, patella, or Achilles tendon. Methodological quality assessment was evaluated with the Newcastle-Ottawa Scale. Results In total, 16 full-text articles met the criteria for inclusion, of which the majority were case-control studies with heterogeneous methodological quality. No studies on Achilles tendinopathy were found. Mechanical algometry was the predominant quantitative sensory testing used. Lowered pressure pain threshold was observed across different tendinopathies at the site of tendinopathy, as well as at other sites, the latter being suggestive of central sensitization. Conclusion Although more research on sensory abnormalities is warranted, it appears likely that there is an association between persistent tendon pain and sensitization of the nervous system. This evidence is primarily from studies of upper-limb tendinopathy, and caution should be exercised with inference to lower-limb tendinopathy. J Orthop Sports Phys Ther 2015;45(11):864-875. Epub 21 Sep 2015. doi:10.2519/jospt.2015.5895.

Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B–induced local skin hypersensitization in healthy subjects: a machine-learned analysis

PubMed Central

Lötsch, Jörn; Geisslinger, Gerd; Heinemann, Sarah; Lerch, Florian; Oertel, Bruno G.; Ultsch, Alfred

2018-01-01

Abstract The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models. PMID:28700537

Low back related leg pain: an investigation of construct validity of a new classification system.

PubMed

Schäfer, Axel G M; Hall, Toby M; Rolke, Roman; Treede, Rolf-Detlef; Lüdtke, Kerstin; Mallwitz, Joachim; Briffa, Kathryn N

2014-01-01

Leg pain is associated with back pain in 25-65% of all cases and classified as somatic referred pain or radicular pain. However, distinction between the two may be difficult as different pathomechanisms may cause similar patterns of pain. Therefore a pathomechanism based classification system was proposed, with four distinct hierarchical and mutually exclusive categories: Neuropathic Sensitization (NS) comprising major features of neuropathic pain with sensory sensitization; Denervation (D) arising from significant axonal compromise; Peripheral Nerve Sensitization (PNS) with marked nerve trunk mechanosensitivity; and Musculoskeletal (M) with pain referred from musculoskeletal structures. To investigate construct validity of the classification system. Construct validity was investigated by determining the relationship of nerve functioning with subgroups of patients and asymptomatic controls. Thus somatosensory profiles of subgroups of patients with low back related leg pain (LBRLP) and healthy controls were determined by a comprehensive quantitative sensory test (QST) protocol. It was hypothesized that subgroups of patients and healthy controls would show differences in QST profiles relating to underlying pathomechanisms. 77 subjects with LBRLP were recruited and classified in one of the four groups. Additionally, 18 age and gender matched asymptomatic controls were measured. QST revealed signs of pain hypersensitivity in group NS and sensory deficits in group D whereas Groups PNS and M showed no significant differences when compared to the asymptomatic group. These findings support construct validity for two of the categories of the new classification system, however further research is warranted to achieve construct validation of the classification system as a whole.

Exercise increases pressure pain tolerance but not pressure and heat pain thresholds in healthy young men.

PubMed

Vaegter, H B; Hoeger Bement, M; Madsen, A B; Fridriksson, J; Dasa, M; Graven-Nielsen, T

2017-01-01

Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. On three different days, 20 healthy young men performed two submaximal isometric knee extensions (30% maximal voluntary contraction in 3 min) and a control condition (quiet rest). Before and immediately after exercise and rest, the sensitivity to heat pain and pressure pain was assessed in randomized and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. Cuff pressure pain tolerance was significantly increased after exercise compared with baseline and rest (p < 0.05). Compared with rest, cPPT and HPT were not significantly increased by exercise. No significant correlation between exercise-induced changes in HPT and cPPT was found. Test-retest reliability before and after the rest condition was better for cPPT and CPTT (intraclass correlation > 0.77) compared with HPT (intraclass correlation = 0.54). The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. The effect of isometric exercise on pain tolerance may be relevant for patients in chronic musculoskeletal pain as a pain-coping strategy. WHAT DOES THIS STUDY ADD?: The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the heat and pressure pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. © 2016 European Pain Federation - EFIC®.

Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation.

PubMed

Andersen, Hjalte H; Lo Vecchio, Silvia; Gazerani, Parisa; Arendt-Nielsen, Lars

2017-09-01

Despite being a ubiquitous animal pain model, the natural TRPA1-agonist allyl isothiocyanate (AITC, also known as "mustard oil") has only been sparsely investigated as a potential human surrogate model of pain, sensitization, and neurogenic inflammation. Its dose-response as an algogenic, sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, and 90%) and vehicle (paraffin) were applied for 5 minutes to 3 × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed. In addition, a comprehensive battery of quantitative sensory tests was conducted, including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was quantified using full-field laser perfusion imaging. Erythema and hyperpigmentation were assessed before, immediately after, and ≈64 hours after AITC exposure. AITC induced significant dose-dependent, moderate-to-severe spontaneous burning pain, mechanical and heat hyperalgesia, and dynamic mechanical allodynia (P < 0.05). No significant differences in induced pain hypersensitivity were observed between the 50% and 90% AITC concentrations. Acute and prolonged inflammation was evoked by all concentrations, and assessments by full-field laser perfusion imaging demonstrated a significant dose-dependent increase with a ceiling effect from 50% to 90%. Topical AITC application produces pain and somatosensory sensitization in a dose-dependent manner with optimal concentrations recommended to be >10% and ≤50%. The model is translatable to humans and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics, and anti-inflammatory compounds or for exploratory clinical purposes, eg, loss- or gain-of-function in peripheral neuropathies.

Deep pain sensitivity is correlated with oral-health-related quality of life but not with prosthetic factors in complete denture wearers

PubMed Central

COSTA, Yuri Martins; PORPORATTI, André Luís; HILGENBERG-SYDNEY, Priscila Brenner; BONJARDIM, Leonardo Rigoldi; CONTI, Paulo César Rodrigues

2015-01-01

ABSTRACT Low pressure Pain Threshold (PPT) is considered a risk factor for Temporomandibular Disorders (TMD) and is influenced by psychological variables. Objectives To correlate deep pain sensitivity of masticatory muscles with prosthetic factors and Oral-Health-Related Quality of Life (OHRQoL) in completely edentulous subjects. Material and Methods A total of 29 complete denture wearers were recruited. The variables were: a) Pressure Pain Threshold (PPT) of the masseter and temporalis; b) retention, stability, and tooth wear of dentures; c) Vertical Dimension of Occlusion (VDO); d) Oral Health Impact Profile (OHIP) adapted to orofacial pain. The Kolmogorov-Smirnov test, the Pearson Product-Moment correlation coefficient, the Spearman Rank correlation coefficient, the Point-Biserial correlation coefficient, and the Bonferroni correction (α=1%) were applied to the data. Results The mean age (standard deviation) of the participants was of 70.1 years (9.5) and 82% of them were females. There were no significant correlations with prosthetic factors, but significant negative correlations were found between the OHIP and the PPT of the anterior temporalis (r=-0.50, 95% CI-0.73 to 0.17, p=0.005). Discussion The deep pain sensitivity of masticatory muscles in complete dentures wearers is associated with OHRQoL, but not with prosthetic factors. PMID:26814457

Perplexing purpura in two females: Rare case of autoerythrocyte sensitization syndrome

PubMed Central

Tainwala, Ram R.; Phiske, Meghna; Raghuwanshi, Abhijith; Mathapati, Sukesh; Manjare, Ashwini K.; Jerajani, Hemangi R.

2013-01-01

Autoerythrocyte sensitization syndrome is a psychologically induced painful bruising condition. Two female, 19 and 30-year-old presented with recurrent episodes of painful ecchymotic bruising over accessible areas of body. In the younger female, episodes were since 3 years and were precipitated by stress and trivial trauma. The elder female presented with similar lesions since 3 months which were spontaneous in presentation. There were no obvious psychiatric manifestations in either. Clinically, ecchymotic changes in various stages of development were seen. Routine hemogram and coagulation profile were normal. Histopathology showed extravasated erythrocytes, perivascular neutrophils and fibrinoid deposition. Intradermal injection of autologous whole blood produced a painful ecchymotic reaction after 2 h similar to the presenting lesions. Psychiatric evaluation revealed mild mixed depression – anxiety disorder in the younger female while the latter revealed no abnormalities. The diagnosis of autoerythrocyte sensitization syndrome was made based on clinical history and findings, positive autoerythrocyte sensitization test, psychiatric evaluation and absence of any other clinical or laboratory pathology. PMID:24350012

Musical Agency during Physical Exercise Decreases Pain.

PubMed

Fritz, Thomas H; Bowling, Daniel L; Contier, Oliver; Grant, Joshua; Schneider, Lydia; Lederer, Annette; Höer, Felicia; Busch, Eric; Villringer, Arno

2017-01-01

Objectives: When physical exercise is systematically coupled to music production, exercisers experience improvements in mood, reductions in perceived effort, and enhanced muscular efficiency. The physiology underlying these positive effects remains unknown. Here we approached the investigation of how such musical agency may stimulate the release of endogenous opioids indirectly with a pain threshold paradigm. Design: In a cross-over design we tested the opioid-hypothesis with an indirect measure, comparing the pain tolerance of 22 participants following exercise with or without musical agency. Method: Physical exercise was coupled to music by integrating weight-training machines with sensors that control music-synthesis in real time. Pain tolerance was measured as withdrawal time in a cold pressor test. Results: On average, participants tolerated cold pain for ~5 s longer following exercise sessions with musical agency. Musical agency explained 25% of the variance in cold pressor test withdrawal times after factoring out individual differences in general pain sensitivity. Conclusions: This result demonstrates a substantial pain reducing effect of musical agency in combination with physical exercise, probably due to stimulation of endogenous opioid mechanisms. This has implications for exercise endurance, both in sports and a multitude of rehabilitative therapies in which physical exercise is effective but painful.

Musical Agency during Physical Exercise Decreases Pain

PubMed Central

Fritz, Thomas H.; Bowling, Daniel L.; Contier, Oliver; Grant, Joshua; Schneider, Lydia; Lederer, Annette; Höer, Felicia; Busch, Eric; Villringer, Arno

2018-01-01

Objectives: When physical exercise is systematically coupled to music production, exercisers experience improvements in mood, reductions in perceived effort, and enhanced muscular efficiency. The physiology underlying these positive effects remains unknown. Here we approached the investigation of how such musical agency may stimulate the release of endogenous opioids indirectly with a pain threshold paradigm. Design: In a cross-over design we tested the opioid-hypothesis with an indirect measure, comparing the pain tolerance of 22 participants following exercise with or without musical agency. Method: Physical exercise was coupled to music by integrating weight-training machines with sensors that control music-synthesis in real time. Pain tolerance was measured as withdrawal time in a cold pressor test. Results: On average, participants tolerated cold pain for ~5 s longer following exercise sessions with musical agency. Musical agency explained 25% of the variance in cold pressor test withdrawal times after factoring out individual differences in general pain sensitivity. Conclusions: This result demonstrates a substantial pain reducing effect of musical agency in combination with physical exercise, probably due to stimulation of endogenous opioid mechanisms. This has implications for exercise endurance, both in sports and a multitude of rehabilitative therapies in which physical exercise is effective but painful. PMID:29387030

Comparative effects of Rauwolfia vomitoria and chlorpromazine on social behaviour and pain

PubMed Central

Bisong, Sunday; Brown, Richard; Osim, Eme

2011-01-01

Background: Rauwolfia vomitoria has been used in Nigeria to manage psychiatric disorders despite orthodox medicine. Aims: This research was therefore aimed at comparing the effects of R. vomitoria, chlorpromazine and reserpine on social behaviour and pain in mice. Materials and Methods: Ninety male CD-1 mice (32 – 38g body weight) were grouped into 3 with 5 subgroups (n=6) each. Mice were given chlorpromazine (0.0, 0.25, 1.0, 2.0, 4.0 mg/kg i.p.), 30 minutes before testing and R. vomitoria (0.0, 0.25, 1.0, 2.0, 4.0 mg/kg, i.p.) and reserpine (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p) 24 hours before testing. Nesting score assessed social behaviour while the tail flick and hot plate analgesiometers assessed pain. Results: Chlorpromazine dose-dependently decreased nesting score (F4,25 = 5.5660; p< 0.01), indicating decreased social behaviour (social loss) in the mice. Although R. vomitoria did not affect nesting score, reserpine decreased the nesting score (social loss). In the pain test, chlorpromazine did not alter tail flick latency but decreased hind paw lick latency in the hot plate at 2.0 and 4.0 mg/kg (p< 0.01), indicating increased pain sensitivity at these doses which may indirectly increase social withdrawal and thus aggravating depression. R. vomitoria however, increased tail flick and hind paw lick latencies in the hot plate test (p< 0.05) indicating decreased pain sensitivity. Reserpine, like R. vomitoria, increased latency of hind paw lick in the hot plate. Conclusion: R. vomitoria has a high potential as an antipsychotic and may have advantage over chlorpromazine; it is not necessary to isolate active components from this herb. PMID:22540065

Non-Acute Coronary Syndrome Anginal Chest Pain

PubMed Central

Agarwal, Megha; Mehta, Puja K.; Merz, C. Noel Bairey

2010-01-01

Anginal chest pain is one of the most common complaints in the outpatient setting. While much of the focus has been on identifying obstructive atherosclerotic coronary artery disease (CAD) as the cause of anginal chest pain, it is clear that microvascular coronary dysfunction (MCD) can also cause anginal chest pain as a manifestation of ischemic heart disease (IHD), and carries an increased cardiovascular risk. Epicardial coronary vasospasm, aortic stenosis, left ventricular hypertrophy, congenital coronary anomalies, mitral valve prolapse and abnormal cardiac nociception can also present as angina of cardiac origin. For non-acute coronary syndrome (ACS) stable chest pain, exercise treadmill testing (ETT) remains the primary tool for diagnosis of ischemia and cardiac risk stratification; however, in certain subsets of patients, such as women, ETT has a lower sensitivity and specificity for identifying obstructive CAD. When combined with an imaging modality, such as nuclear perfusion or echocardiography testing, the sensitivity and specificity of stress testing for detection of obstructive CAD improves significantly. Advancements in stress cardiac magnetic resonance imaging (MRI) enables detection of perfusion abnormalities in a specific coronary artery territory, as well as subendocardial ischemia associated with MCD. Coronary computed tomography angiography (CCTA) enables visual assessment of obstructive CAD, albeit with a higher radiation dose. Invasive coronary angiography (CA) remains the gold standard for diagnosis and treatment of obstructive lesions that cause medically refractory stable angina. Furthermore, in patients with normal coronary angiograms, the addition of coronary reactivity testing (CRT) can help diagnose endothelial dependent and independent microvascular dysfunction. Life-style modification and pharmacologic intervention remains the cornerstone of therapy to reduce morbidity and mortality in patients with stable angina. This review focuses on the pathophysiology, diagnosis, and treatment of stable, non-ACS anginal chest pain. PMID:20380951

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

PubMed Central

Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

Sex differences in thermal detection and thermal pain threshold and the thermal grill illusion: a psychophysical study in young volunteers.

PubMed

Averbeck, Beate; Seitz, Lena; Kolb, Florian P; Kutz, Dieter F

2017-09-01

Sex-related differences in human thermal and pain sensitivity are the subject of controversial discussion. The goal of this study in a large number of subjects was to investigate sex differences in thermal and thermal pain perception and the thermal grill illusion (TGI) as a phenomenon reflecting crosstalk between the thermoreceptive and nociceptive systems. The thermal grill illusion is a sensation of strong, but not necessarily painful, heat often preceded by transient cold upon skin contact with spatially interlaced innocuous warm and cool stimuli. The TGI was studied in a group of 78 female and 58 male undergraduate students and was evoked by placing the palm of the right hand on the thermal grill (20/40 °C interleaved stimulus). Sex-related thermal perception was investigated by a retrospective analysis of thermal detection and thermal pain threshold data that had been measured in student laboratory courses over 5 years (776 female and 476 male undergraduate students) using the method of quantitative sensory testing (QST). To analyse correlations between thermal pain sensitivity and the TGI, thermal pain threshold and the TGI were determined in a group of 20 female and 20 male undergraduate students. The TGI was more pronounced in females than males. Females were more sensitive with respect to thermal detection and thermal pain thresholds. Independent of sex, thermal detection thresholds were dependent on the baseline temperature with a specific progression of an optimum curve for cold detection threshold versus baseline temperature. The distribution of cold pain thresholds was multi-modal and sex-dependent. The more pronounced TGI in females correlated with higher cold sensitivity and cold pain sensitivity in females than in males. Our finding that thermal detection threshold not only differs between the sexes but is also dependent on the baseline temperature reveals a complex processing of "cold" and "warm" inputs in thermal perception. The results of the TGI experiment support the assumption that sex differences in cold-related thermoreception are responsible for sex differences in the TGI.

Central mechanisms of stress-induced headache.

PubMed

Cathcart, S; Petkov, J; Winefield, A H; Lushington, K; Rolan, P

2010-03-01

Stress is the most commonly reported trigger of an episode of chronic tension-type headache (CTTH); however, the causal significance has not been experimentally demonstrated to date. Stress may trigger CTTH through hyperalgesic effects on already sensitized pain pathways in CTTH sufferers. This hypothesis could be partially tested by examining pain sensitivity in an experimental model of stress-induced headache in CTTH sufferers. Such examinations have not been reported to date. We measured pericranial muscle tenderness and pain thresholds at the finger, head and shoulder in 23 CTTH sufferers (CTH-S) and 25 healthy control subjects (CNT) exposed to an hour-long stressful mental task, and in 23 CTTH sufferers exposed to an hour-long neutral condition (CTH-N). Headache developed in 91% of CTH-S, 4% of CNT, and 17% of CTH-N subjects. Headache sufferers had increased muscle tenderness and reduced pain thresholds compared with healthy controls. During the task, muscle tenderness increased and pain thresholds decreased in the CTH-S group compared with CTH-N and CNT groups. Pre-task muscle tenderness and reduction in pain threshold during task were predictive of the development and intensity of headache following task. The main findings are that stress induced a headache in CTTH sufferers, and this was associated with pre-task muscle tenderness and stress-induced reduction in pain thresholds. The results support the hypothesis that stress triggers CTTH through hyperalgesic effects on already increased pain sensitivity in CTTH sufferers, reducing the threshold to noxious input from pericranial structures.

Pain neurophysiology education improves cognitions, pain thresholds, and movement performance in people with chronic whiplash: a pilot study.

PubMed

Van Oosterwijck, Jessica; Nijs, Jo; Meeus, Mira; Truijen, Steven; Craps, Julie; Van den Keybus, Nick; Paul, Lorna

2011-01-01

Chronic whiplash is a debilitating condition characterized by increased sensitivity to painful stimuli, maladaptive illness beliefs, inappropriate attitudes, and movement dysfunctions. Previous work in people with chronic low back pain and chronic fatigue syndrome indicates that pain neurophysiology education is able to improve illness beliefs and attitudes as well as movement performance. This single-case study (A-B-C design) with six patients with chronic whiplash associated disorders (WAD) was aimed at examining whether education about the neurophysiology of pain is accompanied by changes in symptoms, daily functioning, pain beliefs, and behavior. Periods A and C represented assessment periods, while period B consisted of the intervention (pain neurophysiology education). Results showed a significant decrease in kinesiophobia (Tampa Scale for Kinesiophobia), the passive coping strategy of resting (Pain Coping Inventory), self-rated disability (Neck Disability Index), and photophobia (WAD Symptom List). At the same time, significantly increased pain pressure thresholds and improved pain-free movement performance (visual analog scale on Neck Extension Test and Brachial Plexus Provocation Test) were established. Although the current results need to be verified in a randomized, controlled trial, they suggest that education about the physiology of pain is able to increase pain thresholds and improve pain behavior and pain-free movement performance in patients with chronic WAD.

Diagnostic utility of patient history and physical examination data to detect spondylolysis and spondylolisthesis in athletes with low back pain: A systematic review.

PubMed

Grødahl, Linn Helen J; Fawcett, Louise; Nazareth, Madeleine; Smith, Richard; Spencer, Simon; Heneghan, Nicola; Rushton, Alison

2016-08-01

In adolescent athletes, low back pain has a 1-year prevalence of 57% and causes include spondylolysis and spondylolisthesis. An accurate diagnosis enables healing, prevention of progression and return to sport. To evaluate the diagnostic utility of patient history and physical examination data to identify spondylolysis and/or spondylolisthesis in athletes. Systematic review was undertaken according to published guidelines, and reported in line with PRISMA. Key databases were searched up to 13/11/15. athletic population with LBP, patient history and/or physical examination accuracy data for spondylolysis and/or spondylolisthesis, any study design including raw data. Two reviewers independently assessed risk of bias (ROB) using QUADAS-2. A data extraction sheet was pre-designed. Pooling of data and investigation for heterogeneity enabled a qualitative synthesis of data across studies. Of the eight included studies, two were assessed as low ROB, one of which also had no concerns regarding applicability. Age (<20 years) demonstrated 81% sensitivity and 44% specificity and gender (male) 73% sensitivity and 57% specificity for spondylolysis. Difficulty falling asleep, waking up because of pain, pain worse with sitting and walking all have sensitivity >75% for spondylolisthesis. Step-deformity palpation demonstrated 60-88% sensitivity and 87-100% specificity for spondylolisthesis. The one-legged hyperextension test was not supported for spondylolysis (sensitivity 50-73%, specificity 0-87%). No recommendations can be made utilising patient history data. Based on one low ROB study, step deformity palpation may be useful in diagnosing spondylolisthesis. No physical tests demonstrated diagnostic utility for spondylolysis. Further research is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dental attrition models predicting temporomandibular joint disease or masticatory muscle pain versus asymptomatic controls.

PubMed

Seligman, D A; Pullinger, A G

2006-11-01

To determine whether patients with temporomandibular joint disease or masticatory muscle pain can be usefully differentiated from asymptomatic controls using multifactorial classification tree models of attrition severity and/or rates. Measures of attrition severity and rates in patients diagnosed with disc displacement (n = 52), osteoarthrosis (n = 74), or masticatory muscle pain only (n = 43) were compared against those in asymptomatic controls (n = 132). Cross-validated classification tree models were tested for fit with sensitivity, specificity, accuracy and log likelihood accountability. The model for identifying asymptomatic controls only required the three measures of attrition severity (anterior, mediotrusive and laterotrusive posterior) to be differentiated from the patients with a 74.2 +/- 3.8% cross-validation accuracy. This compared with cross-validation accuracies of 69.7 +/- 3.7% for differentiating disc displacement using anterior and laterotrusive attrition severity, 68.7 +/- 3.9% for differentiating disc displacement using anterior and laterotrusive attrition rates, 70.9 +/- 3.3% for differentiating osteoarthrosis using anterior attrition severity and rates, 94.6 +/- 2.1% for differentiating myofascial pain using mediotrusive and laterotrusive attrition severity, and 92.0 +/- 2.1% for differentiating myofascial pain using mediotrusive and anterior attrition rates. The myofascial pain models exceeded the > or =75% sensitivity and > or =90% specificity thresholds recommended for diagnostic tests, and the asymptomatic control model approached these thresholds. Multifactorial models using attrition severity and rates may differentiate masticatory muscle pain patients from asymptomatic controls, and have some predictive value for differentiating intracapsular temporomandibular disorder patients as well.

The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.

PubMed

Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi

2017-10-01

Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.

Ethnic differences in oro-facial somatosensory profiles-quantitative sensory testing in Chinese and Danes.

PubMed

Yang, G; Luo, Y; Baad-Hansen, L; Wang, K; Arendt-Nielsen, L; Xie, Q-F; Svensson, P

2013-11-01

Ethnic differences in pain experiences have been widely assessed in various pathological and experimental conditions. However, limited sensory modalities have been described in previous research, and the affective-motivational factors have so far been estimated to be the main mediator for the ethnic differences. This study aimed to detect the ethnic differences of oro-facial somatosensory profiles related to the sensory-discriminative dimension in healthy volunteers. The standardised quantitative sensory testing battery developed by the German Research Network on Neuropathic Pain was performed bilaterally in the infraorbital and mental regions on age- and gender-matched healthy Chinese and Danes, 29 participants each group. The influences of ethnicity, gender and test site on the somatosensory profile were evaluated by three-way anova. The ethnic disparities were also presented by Z-scores. Compared to Danes, Chinese were more sensitive to thermal detection, thermal pain, mechanical deep pain and mechanical pain rating parameters (P < 0·002) related to small fibre functions. However, the inverse results were observed for mechanical tactile modality related to large fibre function (P < 0·001) and wind-up ratio (P = 0·006). Women presented higher sensitivity compared to men. The mean Z-scores of all the parameters from Chinese group were in the normal zone created by Danish Caucasians' means and SDs. The ethnic disparities in somatosensory profile illustrated the necessity of establishing the reference data for different ethnic groups and possibly individual pain management strategies for the different ethnic groups. © 2013 John Wiley & Sons Ltd.

Thermal and mechanical quantitative sensory testing in Chinese patients with burning mouth syndrome--a probable neuropathic pain condition?

PubMed

Mo, Xueyin; Zhang, Jinglu; Fan, Yuan; Svensson, Peter; Wang, Kelun

2015-01-01

To explore the hypothesis that burning mouth syndrome (BMS) probably is a neuropathic pain condition, thermal and mechanical sensory and pain thresholds were tested and compared with age- and gender-matched control participants using a standardized battery of psychophysical techniques. Twenty-five BMS patients (men: 8, women: 17, age: 49.5 ± 11.4 years) and 19 age- and gender-matched healthy control participants were included. The cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT), in accordance with the German Network of Neuropathic Pain guidelines, were measured at the following four sites: the dorsum of the left hand (hand), the skin at the mental foramen (chin), on the tip of the tongue (tongue), and the mucosa of the lower lip (lip). Statistical analysis was performed using ANOVA with repeated measures to compare the means within and between groups. Furthermore, Z-score profiles were generated, and exploratory correlation analyses between QST and clinical variables were performed. Two-tailed tests with a significance level of 5 % were used throughout. CDTs (P < 0.02) were significantly lower (less sensitivity) and HPTs (P < 0.001) were significantly higher (less sensitivity) at the tongue and lip in BMS patients compared to control participants. WDT (P = 0.007) was also significantly higher at the tongue in BMS patients compared to control subjects . There were no significant differences in MDT and MPT between the BMS patients and healthy subjects at any of the four test sites. Z-scores showed that significant loss of function can be identified for CDT (Z-scores = -0.9±1.1) and HPT (Z-scores = 1.5±0.4). There were no significant correlations between QST and clinical variables (pain intensity, duration, depressions scores). BMS patients had a significant loss of thermal function but not mechanical function, supporting the hypothesis that BMS may be a probable neuropathic pain condition. Further studies including e.g. electrophysiological or imaging techniques are needed to clarify the underlying mechanisms of BMS.

Experimental Psychological Stress on Quantitative Sensory Testing Response in Patients with Temporomandibular Disorders.

PubMed

Araújo Oliveira Ferreira, Dyna Mara; Costa, Yuri Martins; de Quevedo, Henrique Müller; Bonjardim, Leonardo Rigoldi; Rodrigues Conti, Paulo César

2018-05-15

To assess the modulatory effects of experimental psychological stress on the somatosensory evaluation of myofascial temporomandibular disorder (TMD) patients. A total of 20 women with myofascial TMD and 20 age-matched healthy women were assessed by means of a standardized battery of quantitative sensory testing. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR), and pressure pain threshold (PPT) were performed on the facial skin overlying the masseter muscle. The variables were measured in three sessions: before (baseline) and immediately after the Paced Auditory Serial Addition Task (PASAT) (stress) and then after a washout period of 20 to 30 minutes (poststress). Mixed analysis of variance (ANOVA) was applied to the data, and the significance level was set at P = .050. A significant main effect of the experimental session on all thermal tests was found (ANOVA: F > 4.10, P < .017), where detection tests presented an increase in thresholds in the poststress session compared to baseline (CDT, P = .012; WDT, P = .040) and pain thresholds were reduced in the stress (CPT, P < .001; HPT, P = .001) and poststress sessions (CPT, P = .005; HPT, P = .006) compared to baseline. In addition, a significant main effect of the study group on all mechanical tests (MPT, WUR, and PPT) was found (ANOVA: F > 4.65, P < .037), where TMD patients were more sensitive than healthy volunteers. Acute mental stress conditioning can modulate thermal sensitivity of the skin overlying the masseter in myofascial TMD patients and healthy volunteers. Therefore, psychological stress should be considered in order to perform an unbiased somatosensory assessment of TMD patients.

Functional Abdominal Pain Patient Subtypes in Childhood Predict Functional Gastrointestinal Disorders with Chronic Pain and Psychiatric Comorbidities in Adolescence and Adulthood

PubMed Central

Walker, Lynn S.; Sherman, Amanda L.; Bruehl, Stephen; Garber, Judy; Smith, Craig A.

2012-01-01

Although pediatric functional abdominal pain (FAP) has been linked to abdominal pain later in life, childhood predictors of long-term outcomes have not been identified. This study evaluated whether distinct FAP profiles based on patterns of pain and adaptation in childhood could be identified and whether these profiles predicted differences in clinical outcomes and central sensitization (wind-up) on average 9 years later. In 843 pediatric FAP patients, cluster analysis was used to identify subgroups at initial FAP evaluation based on profiles of pain severity, gastrointestinal (GI) and non-GI symptoms, pain threat appraisal, pain coping efficacy, catastrophizing, negative affect, and activity impairment. Three profiles were identified: High Pain Dysfunctional, High Pain Adaptive, and Low Pain Adaptive. Logistic regression analyses controlling for age and sex showed that, compared to pediatric patients with the Low Pain Adaptive profile, those with the High Pain Dysfunctional profile were significantly more likely at long-term follow-up to meet criteria for pain-related functional gastrointestinal disorder (FGID) (OR: 3.45; CI: 1.95–6.11), FGID with comorbid non-abdominal chronic pain (OR: 2.6; CI:1.45–4.66), and FGID with comorbid anxiety or depressive psychiatric disorder (OR: 2.84; CI: 1.35–6.00). Pediatric patients with the High Pain Adaptive profile had baseline pain severity comparable to the High Pain Dysfunctional profile, but had outcomes as favorable as the Low Pain Adaptive profile. In laboratory pain testing at follow-up, High Pain Dysfunctional patients exhibited significantly greater thermal wind-up than Low Pain Adaptive patients, suggesting that a subgroup of FAP patients has outcomes consistent with widespread effects of heightened central sensitization. PMID:22721910

Reduced Modulation of Pain in Older Adults After Isometric and Aerobic Exercise.

PubMed

Naugle, Kelly M; Naugle, Keith E; Riley, Joseph L

2016-06-01

Laboratory-based studies show that acute aerobic and isometric exercise reduces sensitivity to painful stimuli in young healthy individuals, indicative of a hypoalgesic response. However, little is known regarding the effect of aging on exercise-induced hypoalgesia (EIH). The purpose of this study was to examine age differences in EIH after submaximal isometric exercise and moderate and vigorous aerobic exercise. Healthy older and younger adults completed 1 training session and 4 testing sessions consisting of a submaximal isometric handgrip exercise, vigorous or moderate intensity stationary cycling, or quiet rest (control). The following measures were taken before and after exercise/quiet rest: 1) pressure pain thresholds, 2) suprathreshold pressure pain ratings, 3) pain ratings during 30 seconds of prolonged noxious heat stimulation, and 4) temporal summation of heat pain. The results revealed age differences in EIH after isometric and aerobic exercise, with younger adults experiencing greater EIH compared with older adults. The age differences in EIH varied across pain induction techniques and exercise type. These results provide evidence for abnormal pain modulation after acute exercise in older adults. This article enhances our understanding of the influence of a single bout of exercise on pain sensitivity and perception in healthy older compared with younger adults. This knowledge could help clinicians optimize exercise as a method of pain management. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Translation and validation of the German version of the Bournemouth Questionnaire for Neck Pain.

PubMed

Soklic, Marina; Peterson, Cynthia; Humphreys, B Kim

2012-01-25

Clinical outcome measures are important tools to monitor patient improvement during treatment as well as to document changes for research purposes. The short-form Bournemouth questionnaire for neck pain patients (BQN) was developed from the biopsychosocial model and measures pain, disability, cognitive and affective domains. It has been shown to be a valid and reliable outcome measure in English, French and Dutch and more sensitive to change compared to other questionnaires. The purpose of this study was to translate and validate a German version of the Bournemouth questionnaire for neck pain patients. German translation and back translation into English of the BQN was done independently by four persons and overseen by an expert committee. Face validity of the German BQN was tested on 30 neck pain patients in a single chiropractic practice. Test-retest reliability was evaluated on 31 medical students and chiropractors before and after a lecture. The German BQN was then assessed on 102 first time neck pain patients at two chiropractic practices for internal consistency, external construct validity, external longitudinal construct validity and sensitivity to change compared to the German versions of the Neck Disability Index (NDI) and the Neck Pain and Disability Scale (NPAD). Face validity testing lead to minor changes to the German BQN. The Intraclass Correlation Coefficient for the test-retest reliability was 0.99. The internal consistency was strong for all 7 items of the BQN with Cronbach α's of .79 and .80 for the pre and post-treatment total scores. External construct validity and external longitudinal construct validity using Pearson's correlation coefficient showed statistically significant correlations for all 7 scales of the BQN with the other questionnaires. The German BQN showed greater responsiveness compared to the other questionnaires for all scales. The German BQN is a valid and reliable outcome measure that has been successfully translated and culturally adapted. It is shorter, easier to use, and more responsive to change than the NDI and NPAD.

Postoperative pain assessment using four behavioral scales in Pakistani children undergoing elective surgery

PubMed Central

Shamim, Faisal; Ullah, Hameed; Khan, Fauzia A.

2015-01-01

Background: Several measurement tools have been used for assessment of postoperative pain in pediatric patients. Self-report methods have limitations in younger children and parent, nurse or physician assessment can be used as a surrogate measure. These tools should be tested in different cultures as pain can be influenced by sociocultural factors. The objective was to assess the inter-rater agreement on four different behavioral pain assessment scales in our local population. Materials and Methods: This prospective, descriptive, observational study was conducted in Pakistan. American Society of Anesthesiologists I and II children, 3-7 years of age, undergoing elective surgery were enrolled. Four pain assessment scales were used, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), Toddler Preschool Postoperative Pain Scale (TPPPS), objective pain scale (OPS), and Face, Legs, Activity, Cry, Consolability (FLACC). After 15 and 60 min of arrival in the postanesthesia care unit (PACU), each child evaluated his/her postoperative pain by self-reporting and was also independently assessed by the PACU nurse, PACU anesthetist and the parent. The sensitivity and specificity of the responses of the four pain assessment scales were compared to the response of the child. Results: At 15 min, sensitivity and specificity were >60% for doctors and nurses on FLACC, OPS, and CHEOPS scales and for FLACC and CHEOPS scale for the parents. Parents showed poor agreement on OPS and TPPS. At 60 min, sensitivity was poor on the OPS scale by all three observers. Nurses showed a lower specificity on FLACC tool. Parents had poor specificity on CHEOPS and rate of false negatives was high with TPPS. Conclusions: We recommend the use of FLACC scale for assessment by parents, nurses, and doctors in Pakistani children aged between 3 and 7. PMID:25829906

Survey of Musculoskeletal Disorders Among Indian Dancers in Mumbai and Mangalore.

PubMed

Nair, Shruti Prabhakaran; Kotian, Shruti; Hiller, Claire; Mullerpatan, Rajani

2018-06-15

Classical Indian dance has earned recognition across the globe; however, the health of dancers who are carrying forth this heritage has not received due attention. Therefore, this study aimed to explore musculoskeletal pain and injury prevailing among Indian dancers in Mumbai and Mangalore. A secondary aim was to compare pain tolerance levels between dancers and non-dancers. Fifty-one dancers trained in different traditional Indian and Western dance forms and 164 recreational dancers were recruited as participants. An indigenous questionnaire was designed and validated by physical therapists across various levels of experience and dancers across various training levels. The questionnaire recorded dance, pain, and injury profiles. Additionally, pain tolerance was evaluated using the Pain Sensitivity Questionnaire among dancers and healthy age- and gender-matched controls (N = 200). Descriptive statistical analysis was performed to present results of the site of current pain, site of past injury, perceived causes of injury, and exercise routine. The Student's t-test was used to compare Pain Sensitivity Questionnaire scores between dancers and non-dancers, and independent one-way ANOVA was used to compare scores among dancers practicing different dance forms. For both current pain and past injury, dancers reported the back (42.5%) followed by the knee (28.3%) and ankle (18.6%) as the most common sites. Stress was the most commonly perceived cause of injury (34.4%), followed by over work (24.7%), tiredness (17.2%), and falls (13.5%). Warm-up exercises were always performed by 43.30% of dancers, whereas only 20% performed stretching after dance. Almost 60% of dancers participated in forms of exercise other than dance, e.g., swimming, yoga, and aerobics. Pain sensitivity was not significantly different between dancers and non-dancers (p = 0.159). Level of training and gender did not influence pain.

Peripheral input and its importance for central sensitization.

PubMed

Baron, Ralf; Hans, Guy; Dickenson, Anthony H

2013-11-01

Many pain states begin with damage to tissue and/or nerves in the periphery, leading to enhanced transmitter release within the spinal cord and central sensitization. Manifestations of this central sensitization are windup and long-term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater evoked responses, increased receptive field sizes, and ongoing stimulus-independent activity; these changes probably underlie the allodynia, hyperalgesia, and spontaneous pain seen in patients. Central sensitization is maintained by continuing input from the periphery, but also modulated by descending controls, both inhibitory and facilitatory, from the midbrain and brainstem. The projections of sensitized spinal neurons to the brain, in turn, alter the processing of painful messages by higher centers. Several mechanisms contribute to central sensitization. Repetitive activation of primary afferent C fibers leads to a synaptic strengthening of nociceptive transmission. It may also induce facilitation of non-nociceptive Aβ fibers and nociceptive Aδ fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia. In postherpetic neuralgia and complex regional pain syndrome, for example, these symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing central sensitization can be particularly difficult. In addition to the medical history, quantitative sensory testing and functional magnetic resonance imaging may be useful, but diagnostic criteria that include both subjective and objective measures of central augmentation are needed. Mounting evidence indicates that treatment strategies that desensitize the peripheral and central nervous systems are required. These should generally involve a multimodal approach, so that therapies may target the peripheral drivers of central sensitization and/or the central consequences. © 2013 American Neurological Association.

Pain sensitivity and tactile spatial acuity are altered in healthy musicians as in chronic pain patients

PubMed Central

Zamorano, Anna M.; Riquelme, Inmaculada; Kleber, Boris; Altenmüller, Eckart; Hatem, Samar M.; Montoya, Pedro

2015-01-01

Extensive training of repetitive and highly skilled movements, as it occurs in professional classical musicians, may lead to changes in tactile sensitivity and corresponding cortical reorganization of somatosensory cortices. It is also known that professional musicians frequently experience musculoskeletal pain and pain-related symptoms during their careers. The present study aimed at understanding the complex interaction between chronic pain and music training with respect to somatosensory processing. For this purpose, tactile thresholds (mechanical detection, grating orientation, two-point discrimination) and subjective ratings to thermal and pressure pain stimuli were assessed in 17 professional musicians with chronic pain, 30 pain-free musicians, 20 non-musicians with chronic pain, and 18 pain-free non-musicians. We found that pain-free musicians displayed greater touch sensitivity (i.e., lower mechanical detection thresholds), lower tactile spatial acuity (i.e., higher grating orientation thresholds) and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. Moreover, we also found that musicians and non-musicians with chronic pain presented lower tactile spatial acuity and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. The significant increment of pain sensitivity together with decreased spatial discrimination in pain-free musicians and the similarity of results found in chronic pain patients, suggests that the extensive training of repetitive and highly skilled movements in classical musicians could be considered as a risk factor for developing chronic pain, probably due to use-dependent plastic changes elicited in somatosensory pathways. PMID:25610384

Neuro magnetic resonance spectroscopy using wavelet decomposition and statistical testing identifies biochemical changes in people with spinal cord injury and pain.

PubMed

Stanwell, Peter; Siddall, Philip; Keshava, Nirmal; Cocuzzo, Daniel; Ramadan, Saadallah; Lin, Alexander; Herbert, David; Craig, Ashley; Tran, Yvonne; Middleton, James; Gautam, Shiva; Cousins, Michael; Mountford, Carolyn

2010-11-01

Spinal cord injury (SCI) can be accompanied by chronic pain, the mechanisms for which are poorly understood. Here we report that magnetic resonance spectroscopy measurements from the brain, collected at 3T, and processed using wavelet-based feature extraction and classification algorithms, can identify biochemical changes that distinguish control subjects from subjects with SCI as well as subdividing the SCI group into those with and without chronic pain. The results from control subjects (n=10) were compared to those with SCI (n=10). The SCI cohort was made up of subjects with chronic neuropathic pain (n=5) and those without chronic pain (n=5). The wavelet-based decomposition of frequency domain MRS signals employs statistical significance testing to identify features best suited to discriminate different classes. Moreover, the features benefit from careful attention to the post-processing of the spectroscopy data prior to the comparison of the three cohorts. The spectroscopy data, from the thalamus, best distinguished control subjects without SCI from those with SCI with a sensitivity and specificity of 0.9 (Percentage of Correct Classification). The spectroscopy data obtained from the prefrontal cortex and anterior cingulate cortex both distinguished between SCI subjects with chronic neuropathic pain and those without pain with a sensitivity and specificity of 1.0. In this study, where two underlying mechanisms co-exist (i.e. SCI and pain), the thalamic changes appear to be linked more strongly to SCI, while the anterior cingulate cortex and prefrontal cortex changes appear to be specifically linked to the presence of pain. Copyright 2010 Elsevier Inc. All rights reserved.

Nitroxyl inhibits overt pain-like behavior in mice: role of cGMP/PKG/ATP-sensitive potassium channel signaling pathway

PubMed Central

Staurengo-Ferrari, Larissa; Zarpelon, Ana C.; Longhi-Balbinot, Daniela T.; Marchesi, Mario; Cunha, Thiago M.; Alves-Filho, José C.; Cunha, Fernando Q.; Ferreira, Sergio H.; Casagrande, Rubia; Miranda, Katrina M.; Verri, Waldiceu A.

2014-01-01

Background Several lines of evidence have indicated that nitric oxide (NO) plays complex and diverse roles in modulation of pain/analgesia. However, the roles of charged and uncharged congeners of NO are less well understood. In the present study, the antinociceptive effect of the nitroxyl (HNO) donor, Angeli’s salt (Na2N2O3; AS) was investigated in models of overt pain-like behavior. Moreover, whether the antinociceptive effect of nitroxyl was dependent on the activation of cGMP (cyclic guanosine monophosphate)/PKG (protein kinase G)/ATP-sensitive potassium channels was addressed. Methods The antinociceptive effect of AS was evaluated on phenyl-p-benzoquinone (PBQ)- and acetic acid-induced writhings and via the formalin test. In addition, pharmacological treatments targeting guanylate cyclase (ODQ), PKG (KT5923) and ATP-sensitive potassium channel (glybenclamide) were used. Results PBQ and acetic acid induced significant writhing responses over 20 min. The nociceptive response in these models were significantly reduced in a dose-dependent manner by subcutaneous pre-treatment with AS. Furthermore, AS also inhibited both phases of the formalin test. Subsequently, the inhibitory effect of AS in writhing and flinching responses were prevented by ODQ, KT5823 and glybenclamide, although these inhibitors alone did not alter the writhing score. Furthermore, pretreatment with L-cysteine, an HNO scavenger, confirmed that the antinociceptive effect of AS depends on HNO. Conclusion The present study demonstrates the efficacy of a nitroxyl donor and its analgesic mechanisms in overt pain-like behavior by activating the cGMP/PKG/ATP-sensitive potassium channel (K+) signaling pathway. PMID:24948073

Anti-polymer antibodies are correlated with pain and fatigue severity in patients with fibromyalgia syndrome.

PubMed

Sarzi-Puttini, Piercarlo; Atzeni, Fabiola; Di Franco, Manuela; Lama, Nicola; Batticciotto, Alberto; Iannuccelli, Cristina; Dell'Acqua, Donata; de Portu, Simona; Riccieri, Valeria; Carrabba, Mario; Buskila, Dan; Doria, Andrea; Valesini, Guido

2008-02-01

To investigate the prevalence of antipolymer antibody (APA) in patients with fibromyalgia (FM) and to examine its association with FM severity symptoms. The study population consisted of 79 FM patients and 75 controls: 32 with psoriatic arthritis and 43 with rheumatoid arthritis APA levels were indirectly assayed using a commercial ELISA kit from Corgenix (Westmister, Colorado, USA). Optical density (OD) values were recorded on duplicates of each of the reference and patient samples. Among clinical variables we investigated pain, measured according to visual analog scales (VAS: 0-100), fatigue, stiffness, anxiety, depression, all measured by VAS (0-100), and health status measured by Fibromyalgia Impact Questionnaire (FIQ). Sixteen of the 79 FM patients (20.3%) and 12/78 controls (15.4%) were positive for APAs (P = 0.536). Following ROC analysis, area under curve (AUC) was 0.49 (95% CI: 0.40, 0.58). Focusing on FM patients, we observed a correlation between APA titre and pain (tau: - 0.221; P = 0.020) and fatigue (tau: - 0.205; P = 0.032) at univariate analysis. Binomial regression analysis, controlling for clinical and demographic variables, showed that pain (PPR: 0.923; P = 0.007) and fatigue (PPR: 0.948; P = 0.024) were significantly associated with APA test sensitivity. APA test exhibited a low sensitivity in FM patients and it did not distinguish this group of patients from the controls enrolled in this study. Interestingly, positive APA test prevalence increased with less severe pain or fatigue.

Internal and external factors affecting the development of neuropathic pain in rodents. Is it all about pain?

PubMed

Vissers, K; De Jongh, R; Hoffmann, V; Heylen, R; Crul, B; Meert, T

2003-12-01

It is important to know the factors that will influence animal models of neuropathic pain. A good reproducibility and predictability in different strains of animals for a given test increases the clinical relevance and possible targeting. An obligatory requirement for enabling comparisons of results of different origin is a meticulous definition of the specific sensitivities of a model for neuropathic pain and a description of the test conditions. Factors influencing neuropathic pain behavior can be subdivided in external and internal factors. The most important external factors are; timing of the measurement of pain after induction of neuropathy, circadian rhythms, seasonal influences, air humidity, influence of order of testing, diet, social variables, housing and manipulation, cage density, sexual activity, external stress factors, and influences of the experimenter. The internal factors are related to the type of animal, its genetic background, gender, age, and the presence of homeostatic adaptation mechanisms to specific situations or stress. In practice, the behavioral presentations to pain depend on the combination of genetic and environmental factors such as accepted social behavior. It also depends on the use of genetic manipulation of the animals such as in transgenic animals. These make the interpretation of data even more difficult. Differences of pain behavior between in- and outbred animals will be better understood by using modern analysis techniques. Substrains of animals with a high likelihood for developing neuropathic pain make the unraveling of specific pathophysiological mechanisms possible. Concerning the effect of stress on pain, it is important to differentiate between external and internal stress such as social coping behavior. The individual dealing with this stress is species sensitive, and depends on the genotype and the social learning. In the future, histo-immunological and genetic analysis will highlight similarities of the different pathophysiological mechanisms of pain between different species and human subjects. The final objective for the study of pain is to describe the genetics of the eliciting pain mechanisms in humans and to look for correlations with the knowledge from basic research. Therefore, it is necessary to know the genetic evolution of the different mechanisms in chronic pain. In order to be able to control the clinical predictability of a putative treatment the evolutionary pharmacogenomic structure of specific transmitters and receptors must be clarified.

Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses

PubMed Central

Matre, Dagfinn; Hu, Li; Viken, Leif A.; Hjelle, Ingri B.; Wigemyr, Monica; Knardahl, Stein; Sand, Trond; Nilsen, Kristian Bernhard

2015-01-01

Study Objectives: Sleep restriction (SR) has been hypothesized to sensitize the pain system. The current study determined whether experimental sleep restriction had an effect on experimentally induced pain and pain-elicited electroencephalographic (EEG) responses. Design: A paired crossover study. Intervention: Pain testing was performed after 2 nights of 50% SR and after 2 nights with habitual sleep (HS). Setting: Laboratory experiment at research center. Participants: Self-reported healthy volunteers (n = 21, age range: 18–31 y). Measurements and Results: Brief high-density electrical stimuli to the forearm skin produced pinprick-like pain. Subjective pain ratings increased after SR, but only in response to the highest stimulus intensity (P = 0.018). SR increased the magnitude of the pain-elicited EEG response analyzed in the time-frequency domain (P = 0.021). Habituation across blocks did not differ between HS and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039). Pressure pain threshold of the trapezius muscle region also decreased after SR (P = 0.017). Conclusion: Sleep restriction (SR) increased the sensitivity to pressure pain and to electrically induced pain of moderate, but not low, intensity. The increased electrical pain could not be explained by a difference in habituation. Increased response magnitude is possibly related to reduced processing within the somatosensory cortex after partial SR. Citation: Matre D, Hu L, Viken LA, Hjelle IB, Wigemyr M, Knardahl S, Sand T, Nilsen KB. Experimental sleep restriction facilitates pain and electrically induced cortical responses. SLEEP 2015;38(10):1607–1617. PMID:26194577

Evidence for a central mode of action for etoricoxib (COX-2 inhibitor) in patients with painful knee osteoarthritis.

PubMed

Arendt-Nielsen, Lars; Egsgaard, Line Lindhardt; Petersen, Kristian Kjær

2016-08-01

The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in patients with pain. This randomized, double-blind, placebo-controlled, 2-way crossover, 4-week treatment study investigated the pain mechanisms modulated by etoricoxib in patients with painful knee osteoarthritis. Patients were randomized to group A (60 mg/d etoricoxib followed by placebo) or B (placebo followed by 60 mg/d etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds, temporal summation (TS), and conditioning pain modulation. Clinical readouts were Brief Pain Inventory, WOMAC, painDETECT questionnaire (PD-Q), and time and pain intensity during walking and stair climbing. Etoricoxib as compared with placebo significantly modulated the pressure pain thresholds (P = 0.012, localized sensitization) at the knee and leg (control site) (P = 0.025, spreading sensitization) and TS assessed from the knee (P = 0.038) and leg (P = 0.045). Conditioning pain modulation was not modulated. The Brief Pain Inventory (pain scores), PD-Q, WOMAC, and walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0-day 28), responders and nonresponders were defined. The nonresponders showed a significant association between increased facilitation of TS and increased pain alleviation. None of the other parameters predicted the degree of pain alleviation. Generally, a responder to etoricoxib has the most facilitated TS. In conclusion, etoricoxib (1) modulated central pain modulatory mechanisms and (2) improved pain and function in painful osteoarthritis. Stronger facilitation of TS may indicate a better response to etoricoxib, supporting the central mode-of-action of the drug.

Responsiveness of the cervical Northern American Spine Society questionnaire (NASS) and the Short Form 36 (SF-36) in chronic whiplash.

PubMed

Angst, Felix; Verra, Martin L; Lehmann, Susanne; Gysi, Françoise; Benz, Thomas; Aeschlimann, André

2012-02-01

To determine and compare the sensitivity to change of the condition-specific cervical Northern American Spine Society (NASS) and the generic Short Form 36 (SF-36). Prospective cohort study. One hundred and seventy five patients after whiplash injury. Four-week inpatient interdisciplinary pain management programme. MAIN MEASURES, ANALYSIS: Responsiveness of the NASS and the SF-36 was quantified by effect size and standardized response mean and compared within the same construct by the modified Jacknife test. Ability to detect improvement was compared using sensitivities determined from receiver operating characteristics curves. In pain, the NASS was comparable responsive to the SF-36 at the one-month follow-up (n = 175): effect sizes: 0.62 (NASS) versus 0.61 (SF-36), P = 0.914. The NASS was less responsive than the SF-36 in function: 0.23 versus 0.63, P < 0.001 and in pain+function: 0.35 versus 0.58 (P = 0.001). These relationships remained consistent using standardized response means, at the six-month follow-up (n = 103), and in the comparison of the sensitivities. Sensitivities at one month, pain: 70% (NASS) versus 62% (SF-36), P = 0.234; function: 65% versus 80%, P = 0.002; pain+function: 68% versus 78%, P = 0.035. The six-month data were similar. The generic SF-36 was more responsive in function and equally responsive in pain when compared to the condition-specific NASS. The SF-36 can be recommended as a responsive instrument for measurement of pain and function in chronic whiplash syndrome.

A preclinical physiological assay to test modulation of knee joint pain in the spinal cord: effects of oxycodone and naproxen.

PubMed

Miranda, Jason A; Stanley, Phil; Gore, Katrina; Turner, Jamie; Dias, Rebecca; Rees, Huw

2014-01-01

Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain.

A Preclinical Physiological Assay to Test Modulation of Knee Joint Pain in the Spinal Cord: Effects of Oxycodone and Naproxen

PubMed Central

Miranda, Jason A.; Stanley, Phil; Gore, Katrina; Turner, Jamie; Dias, Rebecca; Rees, Huw

2014-01-01

Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain. PMID:25157947

A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology

PubMed Central

Hess, Erik P; Wells, George A; Jaffe, Allan; Stiell, Ian G

2008-01-01

Background Chest pain is the second most common chief complaint in North American emergency departments. Data from the U.S. suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed, with slightly higher rates reported in a recent Canadian study (4.6% and 6.4%, respectively). Information obtained from the history, 12-lead ECG, and a single set of cardiac enzymes is unable to identify patients who are safe for early discharge with sufficient sensitivity. The 2007 ACC/AHA guidelines for UA/NSTEMI do not identify patients at low risk for adverse cardiac events who can be safely discharged without provocative testing. As a result large numbers of low risk patients are triaged to chest pain observation units and undergo provocative testing, at significant cost to the healthcare system. Clinical decision rules use clinical findings (history, physical exam, test results) to suggest a diagnostic or therapeutic course of action. Currently no methodologically robust clinical decision rule identifies patients safe for early discharge. Methods/design The goal of this study is to derive a clinical decision rule which will allow emergency physicians to accurately identify patients with chest pain who are safe for early discharge. The study will utilize a prospective cohort design. Standardized clinical variables will be collected on all patients at least 25 years of age complaining of chest pain prior to provocative testing. Variables strongly associated with the composite outcome acute myocardial infarction, revascularization, or death will be further analyzed with multivariable analysis to derive the clinical rule. Specific aims are to: i) apply standardized clinical assessments to patients with chest pain, incorporating results of early cardiac testing; ii) determine the inter-observer reliability of the clinical information; iii) determine the statistical association between the clinical findings and the composite outcome; and iv) use multivariable analysis to derive a highly sensitive clinical decision rule to guide triage decisions. Discussion The study will derive a highly sensitive clinical decision rule to identify low risk patients safe for early discharge. This will improve patient care, lower healthcare costs, and enhance flow in our busy and overcrowded emergency departments. PMID:18254973

Can brief measures effectively screen for pain and somatic malingering? Examination of the Modified Somatic Perception Questionnaire and Pain Disability Index.

PubMed

Crighton, Adam H; Wygant, Dustin B; Applegate, Kathryn C; Umlauf, Robert L; Granacher, Robert P

2014-09-01

Recent rise in fraudulent disability claims in the United States has resulted in psychologists being increasingly called upon to use psychological tests to determine whether disability claims based on psychological or somatic/pain complaints are legitimate. To examine two brief measures, Modified Somatic Perception Questionnaire (MSPQ) and the Pain Disability Index (PDI), and their ability to screen for malingering in relation to the Bianchini et al. criteria for malingered pain-related disability published in The Spine Journal (2005). Examined brief self-report measures between litigating and nonlitigating pain samples. We compared 144 disability litigants, predominantly presenting a history of musculoskeletal injuries with psychiatric overlay, with 167 nonlitigating pain patients who were predominantly in treatment for chronic back pain issues and other musculoskeletal conditions. Modified Somatic Perception Questionnaire, Pain Disability Index, Minnesota Multiphasic Personality Inventory-2 Restructured Form, Test of Memory Malingering, Letter Memory Test, Victoria Symptom Validity Test, Structured Interview of Reported Symptoms-second edition, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders somatoform disorders module. We examined a sample of 144 individuals undergoing compensation-seeking evaluations in relation to 167 nonlitigating pain patients. Group differences on both the MSPQ and PDI were calculated, as well as sensitivities, specificities, and positive and negative predictive powers for both measures at selected cutoffs. The results suggest that both the MSPQ and PDI are useful to screen for pain malingering in forensic evaluations, especially the MSPQ, which performed the best in differentiating between the groups. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone scan features in spontaneous knee pain.

PubMed

Vattimo, A; Merlo, F; Bertelli, P; Burroni, L

1992-01-01

In 21 patients with "spontaneous" knee pain, 99mTc-MDP bone scan was found to be more sensitive than clinical and radiographic examination in detecting alterations of the joint components. These alterations were shown by increased radionuclide uptake in the compartments where pain was present, which was most commonly the medial femorotibial compartment, although the femoropatellar compartment was also frequently affected. The authors conclude that bone scan should be the first imaging study performed on the knee in order to establish if further tests are necessary.

Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

PubMed

Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

2016-04-01

Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

Effects of Transcutaneous Electrical Nerve Stimulation on Pain, Pain Sensitivity, and Function in People With Knee Osteoarthritis: A Randomized Controlled Trial

PubMed Central

Vance, Carol Grace T.; Rakel, Barbara A.; Blodgett, Nicole P.; DeSantana, Josimari Melo; Amendola, Annunziato; Zimmerman, Miriam Bridget; Walsh, Deirdre M.

2012-01-01

Background Transcutaneous electrical nerve stimulation (TENS) is commonly used for the management of pain; however, its effects on several pain and function measures are unclear. Objective The purpose of this study was to determine the effects of high-frequency TENS (HF-TENS) and low-frequency TENS (LF-TENS) on several outcome measures (pain at rest, movement-evoked pain, and pain sensitivity) in people with knee osteoarthritis. Design The study was a double-blind, randomized clinical trial. Setting The setting was a tertiary care center. Participants Seventy-five participants with knee osteoarthritis (29 men and 46 women; 31–94 years of age) were assessed. Intervention Participants were randomly assigned to receive HF-TENS (100 Hz) (n=25), LF-TENS (4 Hz) (n=25), or placebo TENS (n=25) (pulse duration=100 microseconds; intensity=10% below motor threshold). Measurements The following measures were assessed before and after a single TENS treatment: cutaneous mechanical pain threshold, pressure pain threshold (PPT), heat pain threshold, heat temporal summation, Timed “Up & Go” Test (TUG), and pain intensity at rest and during the TUG. A linear mixed-model analysis of variance was used to compare differences before and after TENS and among groups (HF-TENS, LF-TENS, and placebo TENS). Results Compared with placebo TENS, HF-TENS and LF-TENS increased PPT at the knee; HF-TENS also increased PPT over the tibialis anterior muscle. There was no effect on the cutaneous mechanical pain threshold, heat pain threshold, or heat temporal summation. Pain at rest and during the TUG was significantly reduced by HF-TENS, LF-TENS, and placebo TENS. Limitations This study tested only a single TENS treatment. Conclusions Both HF-TENS and LF-TENS increased PPT in people with knee osteoarthritis; placebo TENS had no significant effect on PPT. Cutaneous pain measures were unaffected by TENS. Subjective pain ratings at rest and during movement were similarly reduced by active TENS and placebo TENS, suggesting a strong placebo component of the effect of TENS. PMID:22466027

Perceived Pain Extent is Not Associated With Widespread Pressure Pain Sensitivity, Clinical Features, Related Disability, Anxiety, or Depression in Women With Episodic Migraine.

PubMed

Fernández-de-Las-Peñas, Cesar; Falla, Deborah; Palacios-Ceña, María; Fuensalida-Novo, Stella; Arias-Buría, Jose L; Schneebeli, Alessandro; Arend-Nielsen, Lars; Barbero, Marco

2018-03-01

People with migraine present with varying pain extent and an expanded distribution of perceived pain may reflect central sensitization. The relationship between pain extent and clinical features, psychological outcomes, related disability, and pressure pain sensitivity in migraine has been poorly investigated. Our aim was to investigate whether the perceived pain extent, assessed from pain drawings, relates to measures of pressure pain sensitivity, clinical, psychological outcomes, and related disability in women with episodic migraine. A total of 72 women with episodic migraine completed pain drawings, which were subsequently digitized allowing pain extent to be calculated utilising novel software. Pressure pain thresholds were assessed bilaterally over the temporalis muscle (trigeminal area), the cervical spine (extratrigeminal area), and tibialis anterior muscle (distant pain-free area). Clinical features of migraine, migraine-related disability (migraine disability assessment questionnaire [MIDAS]), and anxiety and depression (Hospital Anxiety-Depression Scale [HADS]) were also assessed. Spearman ρ correlation coefficients were computed to reveal correlations between pain extent and the remaining outcomes. No significant associations were observed between pain extent and pressure pain thresholds in trigeminal, extratrigeminal or distant pain-free areas, migraine pain features, or psychological variables including anxiety or depression, and migraine-related disability. Pain extent within the trigeminocervical area was not associated with any of the measured clinical outcomes and not related to the degree of pressure pain sensitization in women with episodic migraine. Further research is needed to determine if the presence of expanded pain areas outside of the trigeminal area can play a relevant role in the sensitization processes in migraine.

Combining presentation high-sensitivity cardiac troponin I and glucose measurements to rule-out an acute myocardial infarction in patients presenting to emergency department with chest pain.

PubMed

Greenslade, J H; Kavsak, P; Parsonage, W; Shortt, C; Than, M; Pickering, J W; Aldous, S; Cullen, L

2015-03-01

The use of high sensitivity troponin (hs-Tn) may enable early rule out of acute myocardial infarction (AMI) for patients presenting to the emergency department (ED) with chest pain. This study evaluated two approaches to the early rule out of AMI; a combination of a presentation hs-Tn <4ng/L and normal glucose at presentation (dual testing) and a presentation hs-Tn troponin below the limit of detection (LoD). We utilised prospectively collected data on adult patients presenting with suspected ACS in two EDs in Australia and New Zealand. Blood samples were taken on presentation and tested for glucose and high sensitivity troponin I. The primary endpoint was index AMI and the secondary endpoint was 30-day acute coronary syndrome (ACS). Sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic accuracy of the dual testing and LoD approaches. Of the 1412 participants, 182 (12.9%) had index AMI. The LoD and the dual testing approach were 100% sensitive for index AMI. The specificity of the dual testing approach (25.2%) was slightly higher than that of the LoD (20.4%). Sensitivity for ACS was similar for the two approaches (96.5% for dual testing and 98.1% for the LoD). The dual testing and LoD approach identified all patients with index AMI and could be used to reduce the proportion of patients requiring lengthy assessment and inpatient admission. Further investigation is still required to rule out unstable angina pectoris in patients identified as low risk. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Cold hypersensitivity increases with age in mice with sickle cell disease.

PubMed

Zappia, Katherine J; Garrison, Sheldon R; Hillery, Cheryl A; Stucky, Cheryl L

2014-12-01

Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. In addition, both humans and mice with SCD experience heightened cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization or its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Furthermore, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the transient receptor potential melastatin 8 (Trpm8) and transient receptor potential ankyrin 1 (Trpa1) channels, as well as the 2-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk10), and TRAAK (Kcnk4). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes, and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Mechanical sensitivity and psychological factors in patients with burning mouth syndrome.

PubMed

Honda, Mika; Iida, Takashi; Kamiyama, Hirona; Masuda, Manabu; Kawara, Misao; Svensson, Peter; Komiyama, Osamu

2018-05-18

The aim of this study was to compare mechanical sensitivity on the tongue using quantitative sensory testing (QST) and psychological factors using the General Health Questionnaire (GHQ) between burning mouth syndrome (BMS) patients and healthy participants. Participants comprised 20 female BMS patients (68.1 ± 7.4 years) and 20 healthy females (65.4 ± 4.6 years). Psychological factors were evaluated with GHQ. Tactile detection thresholds (TDT) and filament-prick pain detection thresholds (FPT) were used to evaluate mechanical sensitivity on the tongue in all participants. TDT and FPT were measured on the tongue within both the painful area and the non-painful area in BMS patients, and on the tongue on both sides in healthy participants. As controls, TDT and FPT were measured with Semmes-Weinstein monofilaments on the skin of the mentum and palm in all participants. GHQ scores were significantly higher in BMS patients than in healthy participants (P = 0.024). No significant differences in TDT or FPT on the tongue, mentum, or palm were seen between BMS patients and healthy participants (P > 0.05). BMS patients showed no significant differences in TDT or FPT between the painful and non-painful areas on the tongue (P > 0.05). There were no significant correlations among TDT/FPT and GHQ score in BMS patients (P > 0.05). These findings could indicate a more important role for psychological factors than mechanical sensitivity in BMS pathophysiology. Pain on the tongue in elderly female patients with BMS may be more related to psychological factors.

Physical performance measurement in persons with patellofemoral osteoarthritis: A pilot study.

PubMed

Hoglund, Lisa T; Lockard, Margery A; Barbe, Mary F; Hillstrom, Howard J; Song, Jinsup; Reinus, William R; Barr-Gillespie, Ann E

2015-01-01

Patellofemoral osteoarthritis (PFOA) is associated with pain and decreased self-reported function. The impact of PFOA on actual physical performance is currently unknown. To investigate the impact of PFOA on physical performance and pain. Eight participants aged 40-65 years with bilateral, symptomatic, radiographic PFOA and 7 age- and gender-matched pain-free control participants without radiographic PFOA were studied. Physical performance was measured with the Timed-Up-and-Go (TUG) and 50-foot Fast-Paced-Walk (FPW) tests. Dependent variables included time to complete the TUG and FPW; pretest-posttest change in pain intensity (TUG and FPW); and self-reports of perceived knee pain, stiffness, and physical function. Data were analyzed with nonparametric statistics. The PFOA group TUG time was longer than the control group (p=0.01). No difference between groups was found for FPW time. Pretest-posttest pain increased for the TUG and FPW in PFOA participants (p< 0.05). The PFOA group reported greater knee pain, stiffness, and less physical function than controls (previous 48 hours) (p < 0.01). Symptomatic, radiographic PFOA is associated with increased pain during the TUG and FPW tests and longer time required to complete the TUG. The TUG may be a more sensitive test of physical performance in PFOA.

Sex-dependent effects of cannabis-induced analgesia.

PubMed

Cooper, Ziva D; Haney, Margaret

2016-10-01

Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans. This retrospective analysis compared the analgesic, subjective and physiological effects of active cannabis (3.56-5.60% THC) and inactive cannabis (0.00% THC) in male (N=21) and female (N=21) cannabis smokers under double-blind, placebo-controlled conditions. Pain response was measured using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4°C); times to report pain (pain sensitivity) and withdraw the hand (pain tolerance) were recorded. Subjective drug ratings were also measured. Among men, active cannabis significantly decreased pain sensitivity relative to inactive cannabis (p<0.01). In women, active cannabis failed to decrease pain sensitivity relative to inactive. Active cannabis increased pain tolerance in both men women immediately after smoking (p<0.001); a trend was observed for differences between men and women (p<0.10). Active cannabis also increased subjective ratings of cannabis associated with abuse liability ('Take again,' 'Liking,' 'Good drug effect'), drug strength, and 'High' relative to inactive in both men and women (p<0.01). These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women. These sex-dependent differences are independent of cannabis-elicited subjective effects associated with abuse-liability, which were consistent between men and women. As such, sex-dependent differences in cannabis's analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sex-Dependent Effects Of Cannabis-Induced Analgesia

PubMed Central

Cooper, Ziva D.; Haney, Margaret

2016-01-01

Background Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans. Methods This retrospective analysis compared the analgesic, subjective and physiological effects of active cannabis (3.56 - 5.60% THC) and inactive cannabis (0.00% THC) in male (N = 21) and female (N = 21) cannabis smokers under double-blind, placebo-controlled conditions. Pain response was measured using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4°C); times to report pain (pain sensitivity) and withdraw the hand (pain tolerance) were recorded. Subjective drug ratings were also measured. Results Among men, active cannabis significantly decreased pain sensitivity relative to inactive cannabis (p < 0.01). In women, active cannabis failed to decrease pain sensitivity relative to inactive. Active cannabis increased pain tolerance in both men women immediately after smoking (p < 0.001); a trend was observed for differences between men and women (p < 0.10). Active cannabis also increased subjective ratings of cannabis associated with abuse liability (‘Take again,’ ‘Liking,’ ‘Good drug effect’), drug strength, and ‘High’ relative to inactive in both men and women (p < 0.01). Conclusions These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women. These sex-dependent differences are independent of cannabis-elicited subjective effects associated with abuse-liability, which were consistent between men and women. As such, sex-dependent differences in cannabis's analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief. PMID:27522535

Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model.

PubMed

Chaloner, Aaron; Greenwood-Van Meerveld, Beverley

2013-03-01

Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal disorder, which is more commonly diagnosed in women. Female IBS patients frequently report a history of early life adversity (ELA); however, sex differences in ELA-induced visceral pain and the role of ovarian hormones have yet to be investigated. Therefore, we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were exposed to different pairings of an odor and shock to control for trauma predictability. In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal distension. Following ovariectomy and estradiol replacement in a separate group of rats, the visceral sensitivity was quantified. We found that females that received unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast, visceral sensitivity was not significantly different following ELA in adult males. Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas estradiol replacement reestablished visceral hypersensitivity in the unpredictable group. This study is the first to show sex-related differences in visceral sensitivity following unpredictable ELA. Our data highlight the activational effect of estradiol as a pivotal mechanism in maintaining visceral hypersensitivity. This article directly implicates a critical role for ovarian hormones in maintaining visceral hypersensitivity following ELA, specifically identifying the activational effect of estradiol as a key modulator of visceral sensitivity. These data suggest that ELA induces persistent functional abdominal pain in female IBS patients through an estrogen-dependent mechanism. Copyright © 2013 American Pain Society. All rights reserved.

Content validity of manual spinal palpatory exams - A systematic review

PubMed Central

Najm, Wadie I; Seffinger, Michael A; Mishra, Shiraz I; Dickerson, Vivian M; Adams, Alan; Reinsch, Sibylle; Murphy, Linda S; Goodman, Arnold F

2003-01-01

Background Many health care professionals use spinal palpatory exams as a primary and well-accepted part of the evaluation of spinal pathology. However, few studies have explored the validity of spinal palpatory exams. To evaluate the status of the current scientific evidence, we conducted a systematic review to assess the content validity of spinal palpatory tests used to identify spinal neuro-musculoskeletal dysfunction. Methods Review of eleven databases and a hand search of peer-reviewed literature, published between 1965–2002, was undertaken. Two blinded reviewers abstracted pertinent data from the retrieved papers, using a specially developed quality-scoring instrument. Five papers met the inclusion/exclusion criteria. Results Three of the five papers included in the review explored the content validity of motion tests. Two of these papers focused on identifying the level of fixation (decreased mobility) and one focused on range of motion. All three studies used a mechanical model as a reference standard. Two of the five papers included in the review explored the validity of pain assessment using the visual analogue scale or the subjects' own report as reference standards. Overall the sensitivity of studies looking at range of motion tests and pain varied greatly. Poor sensitivity was reported for range of motion studies regardless of the examiner's experience. A slightly better sensitivity (82%) was reported in one study that examined cervical pain. Conclusions The lack of acceptable reference standards may have contributed to the weak sensitivity findings. Given the importance of spinal palpatory tests as part of the spinal evaluation and treatment plan, effort is required by all involved disciplines to create well-designed and implemented studies in this area. PMID:12734016

Translation and Validation of the Arabic Version of the Fear-Avoidance Beliefs Questionnaire in Patients With Low Back Pain.

PubMed

Alanazi, Fahad; Gleeson, Peggy; Olson, Sharon; Roddey, Toni

2017-04-01

Prospective cohort study of a cross-cultural low back pain (LBP) questionnaire OBJECTIVE.: The objectives of the present study were to translate and cross-culturally adapt the Fear-Avoidance Beliefs Questionnaire (FABQ) to create a version in Arabic and to test its psychometric properties. The FABQ measures the effects that fear and avoidance beliefs have on work and on physical activity. An FABQ cross-culturally adapted for Arabic readers and speakers was created by forward translation, translation synthesis, and backward translation. Forty patients in Riyadh, Saudi Arabia, with LBP evaluated use of the questionnaire, and 70 patients from the same hospital participated in reliability, validity, and sensitivity studies. To determine test-retest reliability of the Arabic FABQ, patients completed it twice within 48 hours without receiving any active treatment between these two sessions. Patients completed the Arabic FABQ (and three other scales) at baseline and 14 days later to determine its validity and sensitivity. Test-retest reliability was good (FABQ-work: intraclass coefficient [ICC] = 0.74; FABQ-physical activity: ICC = 0.90; FABQ overall: ICC = 0.76). Correlations between the FABQ and three other instruments for measuring pain and disability were weak. The strongest correlation was found at the follow-up session with the Arabic Oswestry Questionnaire (r = 0.283; P ≤ 0.05). Sensitivity to change was low. The translation and adaptation of the Arabic version of the FABQ was successful. Overall, the Arabic FABQ had good test-retest reliability, acceptable construct validity, and low sensitivity to change. The Arabic version of the FABQ shows promise in the assessment of fear-avoidance beliefs among patients with LBP who speak and read Arabic. 3.

The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors.

PubMed

Tomić, Maja A; Pecikoza, Uroš B; Micov, Ana M; Stepanović-Petrović, Radica M

2015-12-01

Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action. The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain. ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P ≤ 0.011), in the tail-flick test in diabetic mice (P ≤ 0.013), and in the writhing test (P ≤ 0.003). GR 127935 (P ≤ 0.038) and AM251 and AM630 (P ≤ 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner. ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.

Neck Flexor and Extensor Muscle Endurance in Subclinical Neck Pain: Intrarater Reliability, Standard Error of Measurement, Minimal Detectable Change, and Comparison With Asymptomatic Participants in a University Student Population.

PubMed

Lourenço, Ana S; Lameiras, Carina; Silva, Anabela G

2016-01-01

The aims of this study were to assess intrarater reliability and to calculate the standard error of measurement (SEM) and minimal detectable change (MDC) for deep neck flexor and neck extensor muscle endurance tests, and compare the results between individuals with and without subclinical neck pain. Participants were students of the University of Aveiro reporting subclinical neck pain and asymptomatic participants matched for sex and age to the neck pain group. Data on endurance capacity of the deep neck flexors and neck extensors were collected by a blinded assessor using the deep neck flexor endurance test and the extensor endurance test, respectively. Intraclass correlation coefficients (ICCs), SEM, and MDC were calculated for measurements taken within a session by the same assessor. Differences between groups for endurance capacity were investigated using a Mann-Whitney U test. The deep neck flexor endurance test (ICC = 0.71; SEM = 6.91 seconds; MDC = 19.15 seconds) and neck extensor endurance test (ICC = 0.73; SEM = 9.84 minutes; MDC = 2.34 minutes) are reliable. No significant differences were found between participants with and without neck pain for both tests of muscle endurance (P > .05). The endurance capacity of the deep neck flexors and neck extensors can be reliably measured in participants with subclinical neck pain. However, the wide SEM and MDC might limit the sensitivity of these tests. Copyright © 2016. Published by Elsevier Inc.

Decreased pain sensitivity due to trimethylbenzene exposure ...

EPA Pesticide Factsheets

Traditionally, human health risk assessments have relied on qualitative approaches for hazard identification, often using the Hill criteria and weight of evidence determinations to integrate data from multiple studies. Recently, the National Research Council has recommended the development of quantitative approaches for evidence integration, including the application of meta-analyses. The following hazard identification case study applies qualitative as well as meta-analytic approaches to trimethylbenzene (TMB) isomers exposure and the potential neurotoxic effects on pain sensitivity. In the meta-analytic approach, a pooled effect size is calculated, after consideration of multiple confounding factors, in order to determine whether the entire database under consideration indicates that TMBs are likely to be a neurotoxic hazard. The pain sensitivity studies included in the present analyses initially seem discordant in their results: effects on pain sensitivity are seen immediately after termination of exposure, appear to resolve 24 hours after exposure, and then reappear 50 days later following foot-shock. Qualitative consideration of toxicological and toxicokinetic characteristics of the TMB isomers suggests that the observed differences between studies are due to testing time and can be explained through a complete consideration of the underlying biology of the effect and the nervous system as a whole. Meta-analyses and –regressions support this conclus

Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation.

PubMed

Jääskeläinen, Satu K; Lindholm, Pauliina; Valmunen, Tanja; Pesonen, Ullamari; Taiminen, Tero; Virtanen, Arja; Lamusuo, Salla; Forssell, Heli; Hagelberg, Nora; Hietala, Jarmo; Pertovaara, Antti

2014-10-01

We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. In healthy subjects, 957C>T influenced both innocuous and noxious thermal detection thresholds that were lowest in 957TT homozygotes (P values from .0277 to .0462). rTMS to S1 cortex had analgesic effect only in 957TT homozygote genotype (P=.0086). In patients, prevalence of 957TT homozygote genotype was higher than in a healthy Finnish population (50% vs 27%; P=.0191). Patients with 957TT genotype reported more severe pain than patients with other genotypes (P=.0351). COMT Val158Met polymorphism was not independently associated with the studied variables. Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain.

PubMed

Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

2005-09-01

Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (degrees C), as well as suprathreshold tonic heat pain intensity (46.5 degrees C for 1 min) measured by 0-10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI -8.8, 42.8), P = 0.19), pressure (2.2 mmHg (-28.7, 33.2), P = 0.89) and heat (-0.3 degrees C (-1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities -0.4 NPS units (95% CI -1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the 'weak' opioid-treated subgroup and the 'strong' opioid-treated subgroup again revealed insignificant results. These results suggest that the administration of 'commonly used' dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients receiving non-opioid analgesia.

Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.

PubMed

Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K

2017-08-30

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a sensitized state. These findings are consistent with the observation that BMP receptor hyperactivation correlates with bone abnormalities and pain sensitization in fibrodysplasia ossificans progressiva (Kitterman et al., 2012). Because nociceptive sensitization is associated with chronic pain, these findings indicate that human BMP pathway components may represent targets for novel pain-relieving drugs. Copyright © 2017 the authors 0270-6474/17/378524-10$15.00/0.

Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway

PubMed Central

Follansbee, Taylor L.; Gjelsvik, Kayla J.; Brann, Courtney L.; McParland, Aidan L.

2017-01-01

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a sensitized state. These findings are consistent with the observation that BMP receptor hyperactivation correlates with bone abnormalities and pain sensitization in fibrodysplasia ossificans progressiva (Kitterman et al., 2012). Because nociceptive sensitization is associated with chronic pain, these findings indicate that human BMP pathway components may represent targets for novel pain-relieving drugs. PMID:28855331

Clinical Spectrum of Autoerythrocyte Sensitization Syndrome: A Series of Five Cases

PubMed Central

Thokchom, Nandakishore Singh; Pradeepa, D.; Hafi, N. A. Bishurul; Verma, Kapila

2018-01-01

Autoerythrocyte sensitization syndrome (Gardner Diamond syndrome or GDS) is a rare syndrome characterized by painful and spontaneous purpura commonly affecting adult women, and is mostly associated with psychiatric illness. Diagnosis is mainly based on clinical presentation, exclusion of other simulating diseases, and psychiatric evaluation. Only few cases have been reported till date. We report five cases of spontaneous purpura with a normal investigation profile, except for iron deficiency anemia in 1 patient, of which three had associated underlying psychiatric illness. Autoerythrocyte sensitization test was positive in all our cases. Patients presenting with painful bruises without significant medical history such as underlying bleeding disorder or drug history or history of trauma should be considered for autoerythrocyte sensitization syndrome, and managed accordingly. The present study is a case series of patients with characteristic features of autoerythrocyte sensitization syndrome, considering the rarity of the reports on its clinical spectra. PMID:29644197

Endogenous Opioid Antagonism in Physiological Experimental Pain Models: A Systematic Review

PubMed Central

Werner, Mads U.; Pereira, Manuel P.; Andersen, Lars Peter H.; Dahl, Jørgen B.

2015-01-01

Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double-blind studies using ʻinhibitoryʼ or ʻsensitizingʼ, physiological test paradigms in healthy human subjects. The databases PubMed and Embase were searched according to predefined criteria. Out of a total of 2,142 records, 63 studies (1,477 subjects [male/female ratio = 1.5]) were considered relevant. Twenty-five studies utilized ʻinhibitoryʼ test paradigms (ITP) and 38 studies utilized ʻsensitizingʼ test paradigms (STP). The ITP-studies were characterized as conditioning modulation models (22 studies) and repetitive transcranial magnetic stimulation models (rTMS; 3 studies), and, the STP-studies as secondary hyperalgesia models (6 studies), ʻpainʼ models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and rTMS. In the remaining 14 conditioning modulation studies either absence of effects or ambiguous effects by MOR-antagonists, were observed. In the STP-studies, no effect of the opioid-blockade could be demonstrated in 5 out of 6 secondary hyperalgesia studies. The direction of MOR-antagonist dependent effects upon pain ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 ʻpainʼ model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect, presumably mediated by an EOS-dependent mechanisms of analgesia and hyperalgesia. PMID:26029906

Effects of a Worksite Supervised Adapted Physical Activity Program on Trunk Muscle Endurance, Flexibility, and Pain Sensitivity Among Vineyard Workers.

PubMed

Balaguier, Romain; Madeleine, Pascal; Rose-Dulcina, Kévin; Vuillerme, Nicolas

2017-01-01

In viticulture, the prevalence of low back pain is particularly high among vineyard workers exposed to sustained and awkward postures. One promising setting for low back pain prevention resides in the implementation of workplace physical activity. This nonrandomized pilot study aims at evaluating the effects of a worksite supervised adapted physical activity program among 17 vineyard workers volunteered to enter either an intervention group (n = 10) or a control group (n = 7).The intervention group followed a physical activity program for 8 weeks involving (1) 15 minutes of warm-up every working day and (2) two weekly 1-hour adapted physical activity sessions targeting trunk muscle endurance and flexibility. The control group was advised to continue normal physical activity. Evaluations were carried out at weeks 0, 4, 8, and 12. Physical capacity was assessed using flexibility tests for the trunk, along with trunk muscle flexor and extensor endurance tests. Finally, pain sensitivity was evaluated by assessing pressure pain thresholds over 14 anatomical locations in the low back region. For the intervention group, the endurance of the trunk extensor and flexor significantly increased from baseline to week 8 as well as the pressure pain thresholds. No change was observed for the control group over the same period. These encouraging results in combination with the high adherence rate set interesting foundations for the promotion of worksite supervised adapted physical activity and, most likely, offer a new promising approach to prevent low back pain among vineyard workers.

Effects of cocoa-enriched diet on orofacial pain in a murine model.

PubMed

Bowden, L N; Rohrs, E L; Omoto, K; Durham, P L; Holliday, L S; Morris, A D; Allen, K D; Caudle, R M; Neubert, J K

2017-06-01

To investigate and discuss the effects of cocoa on orofacial pain. The Department of Orthodontics at the University of Florida (UF). Male and female hairless rats (N=20/group) were tested. Rats were tested using the Orofacial Pain Assessment Device (OPAD) before and after changing their food from the standard chow to a cocoa-enriched or control-equivalent diet. Male rats fed the cocoa diet had a significantly higher operant pain index when tested at 37°C as compared to control diet-fed animals. Female rats on the cocoa diet had a significantly higher pain index when tested at 18°C and 44°C, as compared to animals fed the control diet. Capsaicin-induced pain was inhibited, with cocoa-diet male rats having a significantly higher pain index than control-diet male rats and cocoa-diet female rats at both 37°C and 44°C. Cocoa-diet female rats had a significantly higher pain index at 44°C than control-diet females. Mechanical sensitivity was affected following capsaicin cream, with a significantly decreased tolerated bottle distance in both cocoa- and control-diet animals, but there was no difference between cocoa- and control-diet groups. Using the OPAD operant system, we demonstrated that a diet rich in cocoa was effective in inhibiting neurogenic inflammatory pain in rats. This has implications for the use of novel alternative therapies such as diet modification for pain control. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of Pain Assessment Techniques and Analgesia Efficacy in a Female Guinea Pig (Cavia porcellus) Model of Surgical Pain

PubMed Central

Oliver, Vanessa L; Athavale, Stephanie; Simon, Katherine E; Kendall, Lon V; Nemzek, Jean A; Lofgren, Jennifer L

2017-01-01

Guinea pigs (Cavia porcellus) are a frequently used species in research, often involving potentially painful procedures. Therefore, evidence-based recommendations regarding analgesia are critically needed to optimize their wellbeing. Our laboratory examined the efficacy of carprofen and extended-release (ER) buprenorphine, alone and as a multimodal combination, for relieving postsurgical pain in guinea pigs. Animals were assessed by using evoked (mechanical hypersensitivity), nonevoked (video ethogram, cageside ethogram, time-to-consumption test), and clinical (weight loss) measurements for 96 h during baseline, anesthesia–analgesia, and hysterectomy conditions. In addition, ER buprenorphine was evaluated pharmacologically. Guinea pigs treated with a single analgesic showed increased mechanical sensitivity for at least 96 h and indices of pain according to the video ethogram for as long as 8 h, compared with levels recorded during anesthesia–analgesia. In contrast, animals given both analgesics demonstrated increased mechanical sensitivity and behavioral evidence of pain for only 2 h after surgery compared with anesthesia–analgesia. The cageside ethogram and time-to-consumption tests failed to identify differences between conditions or treatment groups, highlighting the difficulty of identifying pain in guinea pigs without remote observation. Guinea pigs treated with multimodal analgesia or ER buprenorphine lost at least 10% of their baseline weights, whereas weight loss in carprofen animals was significantly lower (3%). Plasma levels for ER buprenorphine exceeded 0.9 ng/mL from 8 to 96 h after injection. Of the 3 analgesia regimens evaluated, multimodal analgesia provided the most effective pain control in guinea pigs. However the weight loss in the ER buprenorphine–treated animals may need to be considered during analgesia selection. PMID:28724492

The Key Role of Pain Catastrophizing in the Disability of Patients with Acute Back Pain.

PubMed

Ramírez-Maestre, C; Esteve, R; Ruiz-Párraga, G; Gómez-Pérez, L; López-Martínez, A E

2017-04-01

This study investigated the role of anxiety sensitivity, resilience, pain catastrophizing, depression, pain fear-avoidance beliefs, and pain intensity in patients with acute back pain-related disability. Two hundred and thirty-two patients with acute back pain completed questionnaires on anxiety sensitivity, resilience, pain catastrophizing, fear-avoidance beliefs, depression, pain intensity, and disability. A structural equation modelling analysis revealed that anxiety sensitivity was associated with pain catastrophizing, and resilience was associated with lower levels of depression. Pain catastrophizing was positively associated with fear-avoidance beliefs and pain intensity. Depression was associated with fear-avoidance beliefs, but was not associated with pain intensity. Finally, catastrophizing, fear-avoidance beliefs, and pain intensity were positively and significantly associated with acute back pain-related disability. Although fear-avoidance beliefs and pain intensity were associated with disability, the results showed that pain catastrophizing was a central variable in the pain experience and had significant direct associations with disability when pain was acute. Anxiety sensitivity appeared to be an important antecedent of catastrophizing, whereas the influence of resilience on the acute back pain experience was limited to its relationship with depression.

Altered Pain Sensitivity in Elderly Women with Chronic Neck Pain

PubMed Central

Uthaikhup, Sureeporn; Prasert, Romchat; Paungmali, Aatit; Boontha, Kritsana

2015-01-01

Background Age-related changes occur in both the peripheral and central nervous system, yet little is known about the influence of chronic pain on pain sensitivity in older persons. The aim of this study was to investigate pain sensitivity in elders with chronic neck pain compared to healthy elders. Methods Thirty elderly women with chronic neck pain and 30 controls were recruited. Measures of pain sensitivity included pressure pain thresholds, heat/cold pain thresholds and suprathreshold heat pain responses. The pain measures were assessed over the cervical spine and at a remote site, the tibialis anterior muscle. Results Elders with chronic neck pain had lower pressure pain threshold over the articular pillar of C5-C6 and decreased cold pain thresholds over the cervical spine and tibialis anterior muscle when compared with controls (p < 0.05). There were no between group differences in heat pain thresholds and suprathreshold heat pain responses (p > 0.05). Conclusion The presence of pain hypersensitivity in elderly women with chronic neck pain appears to be dependent on types of painful stimuli. This may reflect changes in the peripheral and central nervous system with age. PMID:26039149

The lambda sign: a new radiographic indicator of latent syndesmosis instability.

PubMed

Ryan, Ltc Paul; Hills, Maj Chad; Chang, James; Wilson, Cpt David

2014-09-01

Latent syndesmotic instability is a common cause of chronic ankle pain. The diagnosis is not readily apparent on static imaging as the fibula remains reduced. The hypothesis of this study was that a previously undescribed novel finding on coronal MRI (lambda sign) is an independent indicator of latent syndesmosis instability. We also report on the utility of classic radiographic and physical exam findings. A total of 23 patients with latent syndesmotic instability diagnosed via arthroscopy (group I) were compared to a cohort of 40 patients who were found to have a stable syndesmosis during arthroscopy for unrelated conditions (group II). A retrospective chart review was performed evaluating their clinical history, preoperative physical examination, and radiologic findings. The lambda sign is a high intensity signal seen on coronal MR imaging that resembles the Greek letter lambda. All of the physical exam findings tested were statistically significant. Pain at the syndesmosis had the highest sensitivity (83%), while pain reproduced with the proximal squeeze test resulted in the highest specificity (89%). The external rotation stress test had the highest positive predictive value (75%). Of the radiographic examinations performed, only the lambda sign was found to have statistical significance with a sensitivity of 75% and a specificity of 63%. The presence of a lambda sign on the MRI of patients with physical exam findings suggestive of syndesmotic pain was highly sensitive (75%) and specific (85%). The lambda sign noted on the coronal MRI was both sensitive and specific for injuries involving greater than 2 mm of diastasis on arthroscopic stress examination of the syndesmosis. While neither the lambda sign nor any other finding on physical or radiographic examination represented an independent predictor of syndesmotic instability, the presence of a lambda sign in concert with positive physical exam findings might help health care providers determine which patients might benefit from operative intervention or referral. Level III, case control study. © The Author(s) 2014.

Electrodermal responses to words in chronic low back pain patients: a comparison between pain descriptors, other emotional words, and neutral words.

PubMed

Bonnet, Adeline; Naveteur, Janick

2006-10-01

This study examines the electrodermal reactivity of chronic sufferers to emotional words. The hypothesis that patients are over-sensitive to pain descriptors is tested. Electrodermal activity was recorded in 12 chronic low back pain patients and 12 healthy controls during passive viewing of words on a video monitor. These words were pain descriptors, other emotional words, and neutral words, in a pseudo-randomized order. A jingle was associated with the word occurrence. In chronic low back pain patients, skin conductance responses (SCRs) induced by pain descriptors or other emotional words were larger than SCRs induced by neutral words but they did not differ from each other. Patients presented SCRs, which were both larger and faster than those of controls, including following neutral words. There was no significant effect of word type in controls. Skin conductance level and the number of nonspecific fluctuations were larger in patients as compared with controls. The present electrodermal study suggests that chronic pain is linked to an increased reactivity to a wide range of stimuli. Emotional load amplifies the effect. This leads to recommend broad therapeutic management in chronic sufferers. Contrary to expectation derived from classical conditioning, patients did not prove over-sensitive to pain descriptors. This negative finding is discussed at methodologic, physiologic, and psychologic levels.

Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B-induced local skin hypersensitization in healthy subjects: a machine-learned analysis.

PubMed

Lötsch, Jörn; Geisslinger, Gerd; Heinemann, Sarah; Lerch, Florian; Oertel, Bruno G; Ultsch, Alfred

2017-08-16

The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Heart rate variability and pain: associations of two interrelated homeostatic processes.

PubMed

Appelhans, Bradley M; Luecken, Linda J

2008-02-01

Between-person variability in pain sensitivity remains poorly understood. Given a conceptualization of pain as a homeostatic emotion, we hypothesized inverse associations between measures of resting heart rate variability (HRV), an index of autonomic regulation of heart rate that has been linked to emotionality, and sensitivity to subsequently administered thermal pain. Resting electrocardiography was collected, and frequency-domain measures of HRV were derived through spectral analysis. Fifty-nine right-handed participants provided ratings of pain intensity and unpleasantness following exposure to 4 degrees C thermal pain stimulation, and indicated their thresholds for barely noticeable and moderate pain during three exposures to decreasing temperature. Greater low-frequency HRV was associated with lower ratings of 4 degrees C pain unpleasantness and higher thresholds for barely noticeable and moderate pain. High-frequency HRV was unrelated to measures of pain sensitivity. Findings suggest pain sensitivity is influenced by characteristics of a central homeostatic system also involved in emotion.

Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization.

PubMed

Simpson, Norah S; Scott-Sutherland, Jennifer; Gautam, Shiva; Sethna, Navil; Haack, Monika

2017-09-01

Chronic pain conditions are highly co-morbid with insufficient sleep. While the mechanistic relationships between the two are not understood, chronic insufficient sleep may be one pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of three weeks of restricted sleep with limited recovery (five nights of 4-hour sleep/night followed by two nights of 8-hour sleep/night) was compared to three weeks of 8-hour sleep/night (control protocol). Seventeen healthy adults participated, with fourteen completing both three-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared to the control protocol, participants in the sleep-restriction/recovery protocol experienced mild increases in spontaneous pain (p<0.05). Heat-pain thresholds decreased following the first week of sleep restriction (p<0.05), but normalized with longer exposure to sleep restriction. In contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both p<0.05), although only in the last two weeks of the sleep restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

Posttraumatic stress symptoms and the diathesis-stress model of chronic pain and disability in patients undergoing major surgery.

PubMed

Martin, Andrea L; Halket, Eileen; Asmundson, Gordon J G; Flora, David B; Katz, Joel

2010-01-01

To (1) use structural equation modeling (SEM) to examine relationships proposed in Turk's diathesis-stress model of chronic pain and disability as well as (2) investigate what role, if any, posttraumatic stress symptoms (PTSS) play in predicting pain disability, relative to some of the other factors in the model. The study sample consisted of 208 patients scheduled for general surgery, 21 to 60 years of age (mean age=47.18 y, SD=9.72 y), who reported experiencing persistent pain for an average of 5.56 years (SD=7.90 y). At their preadmission hospital visit, patients completed the Anxiety Sensitivity Index, Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale-20, Pain Disability Index, posttraumatic stress disorder Checklist, and rated the average intensity of their pain (0 to 10 numeric rating scale). SEM was used to test a model of chronic pain disability and to explore potential relationships between PTSS and factors in the diathesis-stress model. SEM results provided support for a model in which anxiety sensitivity predicted fear of pain and catastrophizing, fear of pain predicted escape/avoidance, and escape/avoidance predicted pain disability. Results also provided support for a feedback loop between disability and fear of pain. SEM analyses provided preliminary support for the inclusion of PTSS in the diathesis-stress model, with PTSS accounting for a significant proportion of the variance in pain disability. Results provide empirical support for aspects of Turk's diathesis-stress model in a sample of patients with persistent pain. Findings also offer preliminary support for the role of PTSS in fear-avoidance models of chronic pain.

Central sensitization: Implications for the diagnosis and treatment of pain

PubMed Central

Woolf, Clifford J

2010-01-01

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and postsurgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk both of developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity. PMID:20961685

Relationship of Pain and Ancestry in African American Women

PubMed Central

Robbins, John A.; Qi, Lihong; Garcia, Lorena; Younger, Jarred W.; Seldin, Michael F.

2015-01-01

Background African Americans are reported to be more sensitive to pain than European Americans. Pain sensitivity has been shown to be genetically linked in animal models and is likely to be in humans. Methods 11,239 self-identified African American post menopausal women enrolled in the Women’s Health Initiative had percentage African ancestry determined by ancestry informative markers, “Pain Construct” measurements and covariate information. They answered 5 questions about specific types and location of pain, such as joint, neck, low back, headache, and urinary. They also answered 2 questions which were used to derive a “Pain Construct”, a measure of general pain scored on a scale of 1 to 100. Associations were tested in linear regression models adjusting for age, self-reported medical conditions, neighborhood socio-economic status, education, and depression. Results In the unadjusted model of the 5 specific types of pain measures, greater pain perception was associated with a higher proportion of African ancestry. However, some of the specific types of pain measures were no longer associated with African ancestry after adjustment for other study covariates. The Pain Construct was statistically significantly associated with African ancestry in both the unadjusted [Beta = −0.132, 95% confidence interval (C I) = −099 – −0.164; r = −0.075, 95% CI −0.056 – −0.093] and the adjusted models (Beta = −0.069 95% CI = −0.04 – 0.10). Conclusions Greater African ancestry was associated with higher levels of self-reported pain although this accounted for only a minor fraction of the overall variation in the Pain Construct. PMID:25752262

The role of circulating sex hormones in menstrual cycle dependent modulation of pain-related brain activation

PubMed Central

Veldhuijzen, Dieuwke S.; Keaser, Michael L.; Traub, Deborah S.; Zhuo, Jiachen; Gullapalli, Rao P.; Greenspan, Joel D.

2013-01-01

Sex differences in pain sensitivity have been consistently found but the basis for these differences is incompletely understood. The present study assessed how pain-related neural processing varies across the menstrual cycle in normally cycling, healthy females, and whether menstrual cycle effects are based on fluctuating sex hormone levels. Fifteen subjects participated in four test sessions during their menstrual, mid-follicular, ovulatory, and midluteal phases. Brain activity was measured while nonpainful and painful stimuli were applied with a pressure algometer. Serum hormone levels confirmed that scans were performed at appropriate cycle phases in 14 subjects. No significant cycle phase differences were found for pain intensity or unpleasantness ratings of stimuli applied during fMRI scans. However, lower pressure pain thresholds were found for follicular compared to other phases. Pain-specific brain activation was found in several regions traditionally associated with pain processing, including the medial thalamus, anterior and mid-insula, mid-cingulate, primary and secondary somatosensory cortices, cerebellum, and frontal regions. The inferior parietal lobule, occipital gyrus, cerebellum and several frontal regions demonstrated interaction effects between stimulus level and cycle phase, indicating differential processing of pain-related responses across menstrual cycle phases. Correlational analyses indicated that cycle-related changes in pain sensitivity measures and brain activation were only partly explained by varying sex hormone levels. These results show that pain-related cerebral activation varies significantly across the menstrual cycle, even when perceived pain intensity and unpleasantness remain constant. The involved brain regions suggest that cognitive pain or more general bodily awareness systems are most susceptible to menstrual cycle effects. PMID:23528204

Fibromyalgia interacts with age to change the brain☆☆☆

PubMed Central

Ceko, Marta; Bushnell, M. Catherine; Fitzcharles, Mary-Ann; Schweinhardt, Petra

2013-01-01

Although brain plasticity in the form of gray matter increases and decreases has been observed in chronic pain, factors determining the patterns of directionality are largely unknown. Here we tested the hypothesis that fibromyalgia interacts with age to produce distinct patterns of gray matter differences, specifically increases in younger and decreases in older patients, when compared to age-matched healthy controls. The relative contribution of pain duration was also investigated. Regional gray matter was measured in younger (n = 14, mean age 43, range 29–49) and older (n = 14; mean age 55, range 51–60) female fibromyalgia patients and matched controls using voxel-based morphometry and cortical thickness analysis of T1-weighted magnetic resonance images. To examine their functional significance, gray matter differences were compared with experimental pain sensitivity. Diffusion-tensor imaging was used to assess whether white matter changed in parallel with gray matter, and resting-state fMRI was acquired to examine whether pain-related gray matter changes are associated with altered functional connectivity. Older patients showed exclusively decreased gray matter, accompanied by compromised white matter integrity. In contrast, younger patients showed exclusively gray matter increases, namely in the basal ganglia and insula, which were independent of pain duration. Associated white matter changes in younger patients were compatible with gray matter hypertrophy. In both age groups, structural brain alterations were associated with experimental pain sensitivity, which was increased in older patients but normal in younger patients. Whereas more pronounced gray matter decreases in the posterior cingulate cortex were related to increased experimental pain sensitivity in older patients, insular gray matter increases in younger patients correlated with lower pain sensitivity, possibly indicating the recruitment of endogenous pain modulatory mechanisms. This is supported by the finding that the insula in younger patients showed functional decoupling from an important pain-processing region, the dorsal anterior cingulate cortex. These results suggest that brain structure and function shift from being adaptive in younger to being maladaptive in older patients, which might have important treatment implications. PMID:24273710

Perinatal maternal stress and serotonin signaling: effects on pain sensitivity in offspring.

PubMed

Knaepen, Liesbeth; Pawluski, Jodi L; Patijn, Jacob; van Kleef, Maarten; Tibboel, Dick; Joosten, Elbert A

2014-07-01

It has been estimated that 20% of pregnant women are facing perinatal stress and depression. Perinatal maternal stress has been shown to increase pain sensitivity in offspring. For the treatment of their depressive symptoms, pregnant women are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). Since the descending pain inhibitory circuit matures perinatally, perinatal SSRI exposure has been shown to affect pain sensitivity in offspring. In the present review, we summarize experimental and clinical evidence for the effect of perinatal maternal stress and SSRI exposure on pain sensitivity in offspring. Both experimental and clinical studies show the effect of perinatal maternal stress on regulation of the hypothalamic-pituitary-adrenal (HPA) system and the serotonin pain inhibitory system. Alterations in these two systems likely underlie long-term alterations in the development of pain sensitivity. This review sheds light on the effect of perinatal maternal stress and treatment with SSRIs on offspring pain sensitivity, in relation to the developing HPA system and 5-HT signaling. © 2013 Wiley Periodicals, Inc.

Pain sensitivity and temperament in extremely low-birth-weight premature toddlers and preterm and full-term controls.

PubMed

Grunau, R V; Whitfield, M F; Petrie, J H

1994-09-01

High-technology medical care of extremely low-birth-weight (ELBW) infants (< 1001 g) involves repeated medical interventions which are potentially painful and may later affect reaction to pain. At 18 months corrected age (CCA), we examined parent ratings of pain sensitivity and how pain sensitivity ratings related to child temperament and parenting style in 2 groups of ELBW children (49 with a birth weight of 480-800 g and 75 with a birth weight of 801-1000 g) and 2 control groups (42 heavier preterm (1500-2499 g) and 29 full-birth-weight (FBW) children (> 2500 g). Both groups of ELBW toddlers were rated by parents as significantly lower in pain sensitivity compared with both control groups. The relationships between child temperament and pain sensitivity rating varied systematically across the groups. Temperament was strongly related to rated pain sensitivity in the FBW group, moderately related in the heavier preterm and ELBW 801-1000 g groups, and not related in the lowest birth-weight group (< 801 g). Parental style did not mediate ratings of pain sensitivity. The results suggest that parents perceive differences in pain behavior of ELBW toddlers compared with heavier preterm and FBW toddlers, especially for those less than 801 g. Longitudinal research into the development of pain behavior for infants who experience lengthy hospitalization is warranted.

Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo

2014-01-01

Introduction Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. Method 120 individuals with chronic pain were recruited in 4 groups (n=30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M=121 weeks; SD=23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. Results A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (Log rank=15.50; p<.001) and tolerance (Log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p’s<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p’s<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns). Conclusion Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. PMID:25456326

Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

PubMed

Wachholtz, Amy; Gonzalez, Gerardo

2014-12-01

Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p < .001) and tolerance (log rank = 20.11; p < .001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's < .01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p < .05), with the highest tolerance found among opioid naïve control group participants (p's < .001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R = .37; p < .05); but duration of abstinence did not alter sensitivity (ns). Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cluster subgroups based on overall pressure pain sensitivity and psychosocial factors in chronic musculoskeletal pain: Differences in clinical outcomes.

PubMed

Almeida, Suzana C; George, Steven Z; Leite, Raquel D V; Oliveira, Anamaria S; Chaves, Thais C

2018-05-17

We aimed to empirically derive psychosocial and pain sensitivity subgroups using cluster analysis within a sample of individuals with chronic musculoskeletal pain (CMP) and to investigate derived subgroups for differences in pain and disability outcomes. Eighty female participants with CMP answered psychosocial and disability scales and were assessed for pressure pain sensitivity. A cluster analysis was used to derive subgroups, and analysis of variance (ANOVA) was used to investigate differences between subgroups. Psychosocial factors (kinesiophobia, pain catastrophizing, anxiety, and depression) and overall pressure pain threshold (PPT) were entered into the cluster analysis. Three subgroups were empirically derived: cluster 1 (high pain sensitivity and high psychosocial distress; n = 12) characterized by low overall PPT and high psychosocial scores; cluster 2 (high pain sensitivity and intermediate psychosocial distress; n = 39) characterized by low overall PPT and intermediate psychosocial scores; and cluster 3 (low pain sensitivity and low psychosocial distress; n = 29) characterized by high overall PPT and low psychosocial scores compared to the other subgroups. Cluster 1 showed higher values for mean pain intensity (F (2,77)  = 10.58, p < 0.001) compared with cluster 3, and cluster 1 showed higher values for disability (F (2,77)  = 3.81, p = 0.03) compared with both clusters 2 and 3. Only cluster 1 was distinct from cluster 3 according to both pain and disability outcomes. Pain catastrophizing, depression, and anxiety were the psychosocial variables that best differentiated the subgroups. Overall, these results call attention to the importance of considering pain sensitivity and psychosocial variables to obtain a more comprehensive characterization of CMP patients' subtypes.

Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice.

PubMed

Nijs, Jo; Van Houdenhove, Boudewijn; Oostendorp, Rob A B

2010-04-01

Central sensitization plays an important role in the pathophysiology of numerous musculoskeletal pain disorders, yet it remains unclear how manual therapists can recognize this condition. Therefore, mechanism based clinical guidelines for the recognition of central sensitization in patients with musculoskeletal pain are provided. By using our current understanding of central sensitization during the clinical assessment of patients with musculoskeletal pain, manual therapists can apply the science of nociceptive and pain processing neurophysiology to the practice of manual therapy. The diagnosis/assessment of central sensitization in individual patients with musculoskeletal pain is not straightforward, however manual therapists can use information obtained from the medical diagnosis, combined with the medical history of the patient, as well as the clinical examination and the analysis of the treatment response in order to recognize central sensitization. The clinical examination used to recognize central sensitization entails the distinction between primary and secondary hyperalgesia. Copyright 2009 Elsevier Ltd. All rights reserved.

Sensitive Troponin I and Stress Testing in the Emergency Department for the Early Management of Chest Pain Using 2-Hour Protocol.

PubMed

Dadkhah, Shahriar; Almuwaqqat, Zakaria; Sulaiman, Samian; Husein, Husein; Nguyen, Quang; Ali, Saad; Taskesen, Tuncay

2017-09-01

Despite improvements in identifying high-risk patients with non-ST segment ACS (acute coronary syndrome), low risk patients presenting with atypical chest pain and non-diagnostic Electrocardiogram (ECG) continued to undergo unnecessary admissions and testing. Since 1992, our chest pain protocol included using 4-hour serial biomarkers from ED admission in combination with stress testing to evaluate these patients. Our study aimed at determining whether a new accelerated diagnostic protocol using sensitive cardiac troponin I (cTnI) 2 hours after admission to the ED followed by stress testing is safe and effective in emergency settings, allowing for appropriate triage, earlier discharge and reducing costs. We conducted a single center randomized trial at Presence St. Francis Hospital Chest pain center in Evanston, Illinois enrolling sixty-four consecutive patients with atypical chest pain and non-diagnostic ECG, participants were randomized to accelerated 2 hrs protocol or our pre-existing 4-hrs protocol. Sixty patients completed the protocol and were randomized to either a 2-hour (29 patients) or 4-hour protocol using both I-STAT and PATHFAST cTnI (31 Patients). Troponin I was evaluated at 0 and at 2 hours from ED presentation with and additional draw for patients in the 4-hour rule out-group. Patients with normal serial biomarkers were then evaluated with stress testing and qualified for earlier discharge if the stress test was negative, while those with a positive biomarker at any time were admitted. Thirty-six patients had exercise treadmill stress test and 24 patients had either nuclear or Echo stress test. Fifty-three patients had a normal stress test and were discharged home. One patient in the 4-hour group with normal serial troponins developed ventricular tachycardia/fibrillation during the recovery period of a regular stress test. Six patients had a positive PATHFAST cTnI and a normal I-STAT cTnI at 2-hours. Two out of these six patients evaluated by coronary angiography. One patient had severe tortuous coronaries but no significant obstructive lesion and one had a severe CAD who needed Coronary artery bypass grafting (CABG). Three of the six patients had a normal stress test and one patient decided to leave without further testing. None of the patients with a normal stress test had a major cardiac event or adverse cardiac outcome at six-month follow up. This study demonstrates that the 2 hours accelerated protocol using high sensitivity Troponin assay at 0 and 2 hours with comprehensive clinical evaluation and ECG followed by stress testing might be successful in identifying low-risk patient population who may benefit from early discharge from ED reducing associated costs and length of stay.

Continuous positive airway pressure in severe obstructive sleep apnea reduces pain sensitivity.

PubMed

Khalid, Imran; Roehrs, Timothy A; Hudgel, David W; Roth, Thomas

2011-12-01

To evaluate effects of CPAP on pain sensitivity in severe OSA patients. Within-subject treatment study. Hospital-based sleep disorders center. Twelve severe OSA patients (7 men, 5 women), 50.2 ± 12.5 years, with no pain. The morning after a diagnostic nocturnal polysomnogram (NPSG), patients underwent a training session of finger withdrawal latency (FWL) testing to a radiant heat stimulus, a validated human behavioral model of thermal nociception. Baseline FWL in seconds was obtained after the training session. CPAP pressure was titrated on a second night in the laboratory. Two nights after titration, patients returned to sleep in the laboratory on CPAP. FWL was tested in the morning after awakening, after 6-8 wks of CPAP use, and finally (within 6-8 weeks) after 2 nights of discontinuation of CPAP. Mean FWL in seconds (sec) was compared using MANOVAs with nights as the within subject variable. Apnea-hypopnea index (AHI) decreased from 50.9 ± 14.5 to 1.4 ± 1.0 with CPAP, and sleep continuity improved. In parallel, FWL increased significantly from a mean baseline of 9.8 ± 1.3 sec to 13.7 ± 5.1 sec (P = 0.01) and with continued CPAP use (5.1 ± 2.3 h nightly) for 6-8 weeks FWL remained elevated (21.1 ± 16.2 sec). After the 2-night CPAP discontinuation, apnea/hypopneas returned and sleep was fragmented (AHI = 32.6 ± 19.8). FWL decreased to 11.6 ± 5.9 sec relative to intermediate-term CPAP use (P = 0.03). CPAP treatment reduces pain sensitivity in OSA patients. Future studies will focus on patients with OSA and chronic pain and identify mediating mechanisms.

Racial and ethnic differences in experimental pain sensitivity: systematic review and meta-analysis.

PubMed

Kim, Hee Jun; Yang, Gee Su; Greenspan, Joel D; Downton, Katherine D; Griffith, Kathleen A; Renn, Cynthia L; Johantgen, Meg; Dorsey, Susan G

2017-02-01

Our objective was to describe the racial and ethnic differences in experimental pain sensitivity. Four databases (PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO) were searched for studies examining racial/ethnic differences in experimental pain sensitivity. Thermal-heat, cold-pressor, pressure, ischemic, mechanical cutaneous, electrical, and chemical experimental pain modalities were assessed. Risk of bias was assessed using the Agency for Healthcare Research and Quality guideline. Meta-analysis was used to calculate standardized mean differences (SMDs) by pain sensitivity measures. Studies comparing African Americans (AAs) and non-Hispanic whites (NHWs) were included for meta-analyses because of high heterogeneity in other racial/ethnic group comparisons. Statistical heterogeneity was assessed by subgroup analyses by sex, sample size, sample characteristics, and pain modalities. A total of 41 studies met the review criteria. Overall, AAs, Asians, and Hispanics had higher pain sensitivity compared with NHWs, particularly lower pain tolerance, higher pain ratings, and greater temporal summation of pain. Meta-analyses revealed that AAs had lower pain tolerance (SMD: -0.90, 95% confidence intervals [CIs]: -1.10 to -0.70) and higher pain ratings (SMD: 0.50, 95% CI: 0.30-0.69) but no significant differences in pain threshold (SMD: -0.06, 95% CI: -0.23 to 0.10) compared with NHWs. Estimates did not vary by pain modalities, nor by other demographic factors; however, SMDs were significantly different based on the sample size. Racial/ethnic differences in experimental pain sensitivity were more pronounced with suprathreshold than with threshold stimuli, which is important in clinical pain treatment. Additional studies examining mechanisms to explain such differences in pain tolerance and pain ratings are needed.

Detection of exercise-induced myocardial ischemia from symptomatology experienced during testing in men and women

PubMed Central

D’Antono, Bianca; Dupuis, Gilles; Fortin, Christophe; Arsenault, André; Burelle, Denis

2006-01-01

BACKGROUND AND OBJECTIVES To examine the capacity of angina and related symptoms experienced during exercise-stress testing to detect the presence of ischemia, controlling for other clinical factors. METHOD The authors undertook a prospective study of 482 women and 425 men (mean age 58 years) undergoing exercise stress testing with myocardial perfusion imaging. One hundred forty-six women and 127 men reported chest pain, and of these, 25% of women and 66% of men had myocardial perfusion imaging evidence of ischemia during testing. The present article focuses on patients with chest pain during testing. MAIN OUTCOME MEASURES Outcome measures included chest pain localization, extension, intensity and quality, as well as the presence of various nonpain-related symptoms. Backward logistical regression analyses were performed separately on men and women who had experienced chest pain during testing. RESULTS Men who described their chest pain as ‘heavy’ were 4.6 times more likely to experience ischemia during testing (P=0.039) compared with other men, but this pain descriptor only slightly improved accuracy of prediction beyond that provided by control variables. In women, several symptoms added to the sensitivity of the prediction, such as a numb feeling in the face or neck region (OR 4.5; P=0.048), a numb feeling in the chest area (OR 14.6; P=0.003), muscle tension (OR 5.2; P=0.013), and chest pain that was described as hot or burning (OR 4.3; P=0.014). CONCLUSIONS A more refined evaluation of symptoms experienced during testing was particularly helpful in improving detection of ischemia in women, but not in men. Attention to these symptoms may favour timely diagnosis of myocardial perfusion defects in women. PMID:16639477

Pain catastrophizing mediates the relationship between self-reported strenuous exercise involvement and pain ratings: moderating role of anxiety sensitivity.

PubMed

Goodin, Burel R; McGuire, Lynanne M; Stapleton, Laura M; Quinn, Noel B; Fabian, Lacy A; Haythornthwaite, Jennifer A; Edwards, Robert R

2009-11-01

To investigate the cross-sectional associations among self-reported weekly strenuous exercise bouts, anxiety sensitivity, and their interaction with pain catastrophizing and pain responses to the cold pressor task (CPT) in healthy, ethnically diverse young adults (n = 79). Exercise involvement has been shown to have hypoalgesic effects and cognitive factors may partially explain this effect. Particularly, alterations in pain catastrophizing have been found to mediate the positive pain outcomes of multidisciplinary treatments incorporating exercise. Further, recent evidence suggests that exercise involvement and anxiety sensitivity may act together, as interacting factors, to exert an effect on catastrophizing and pain outcomes; however, further research is needed to clarify the nature of this interaction. Before the CPT, participants were asked to complete the Godin Leisure-Time Exercise Questionnaire, the Beck Depression Inventory, and the Anxiety Sensitivity Index. After the CPT, participants completed a modified version of the Pain Catastrophizing Scale and the Short Form-McGill Pain Questionnaire. At a high level of anxiety sensitivity, controlling for depressive symptoms, CPT immersion time, and sex differences, a bias-corrected (BC), bootstrapped confidence interval revealed that pain catastrophizing significantly mediated the relationship between self-reported weekly strenuous exercise bouts and pain response (95% BC Confidence Interval = -9.558, -0.800 with 1000 resamples). At intermediate and low levels of anxiety sensitivity, no significant mediation effects were found. These findings support that, for pain catastrophizing to mediate the strenuous exercise-pain response relation, individuals must possess a high level of anxiety sensitivity.

The influence of working memory capacity on experimental heat pain.

PubMed

Nakae, Aya; Endo, Kaori; Adachi, Tomonori; Ikeda, Takashi; Hagihira, Satoshi; Mashimo, Takashi; Osaka, Mariko

2013-10-01

Pain processing and attention have a bidirectional interaction that depends upon one's relative ability to use limited-capacity resources. However, correlations between the size of limited-capacity resources and pain have not been evaluated. Working memory capacity, which is a cognitive resource, can be measured using the reading span task (RST). In this study, we hypothesized that an individual's potential working memory capacity and subjective pain intensity are related. To test this hypothesis, we evaluated 31 healthy participants' potential working memory capacity using the RST, and then applied continuous experimental heat stimulation using the listening span test (LST), which is a modified version of the RST. Subjective pain intensities were significantly lower during the challenging parts of the RST. The pain intensity under conditions where memorizing tasks were performed was compared with that under the control condition, and it showed a correlation with potential working memory capacity. These results indicate that working memory capacity reflects the ability to process information, including precise evaluations of changes in pain perception. In this work, we present data suggesting that changes in subjective pain intensity are related, depending upon individual potential working memory capacities. Individual working memory capacity may be a phenotype that reflects sensitivity to changes in pain perception. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Influence of headache frequency on clinical signs and symptoms of TMD in subjects with temple headache and TMD pain

PubMed Central

Anderson, Gary C.; John, Mike T.; Ohrbach, Richard; Nixdorf, Donald R.; Schiffman, Eric L.; Truelove, Edmond S.; List, Thomas

2011-01-01

The relationship of the frequency of temple headache to signs and symptoms of temporomandibular disorders (TMD) was investigated in a subset of a larger convenience sample of community TMD cases. The study sample included: 86 painful TMD, non-headache subjects; 309 painful TMD subjects with varied frequency of temple headaches; and 149 subjects without painful TMD or headache for descriptive comparison. Painful TMD included Research Diagnostic Criteria (RDC) diagnoses of myofascial pain, TMJ arthralgia and TMJ osteoarthritis. Mild to moderate intensity temple headaches were classified by frequency using criteria based on the ICHD-II classification of TTH. Outcomes included TMD signs and symptoms (pain duration, pain intensity, number of painful masticatory sites on palpation, mandibular range of motion), PPTs and temple headache resulting from masticatory provocation tests. Trend analyses across the painful TMD groups showed a substantial trend for aggravation of all of the TMD signs and symptoms associated with increased frequency of the temple headaches. In addition, increased headache frequency showed significant trends associated with reduced PPTs and reported temple headache with masticatory provocation tests. In conclusion, these findings suggest that these headaches may be TMD-related, as well as a possible role for peripheral and central sensitization in TMD patients. PMID:21196079

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Quantitative validation of sensory mapping in persistent postherniorrhaphy inguinal pain patients undergoing triple neurectomy.

PubMed

Bjurström, M F; Álvarez, R; Nicol, A L; Olmstead, R; Amid, P K; Chen, D C

2017-04-01

Neurectomy of the inguinal nerves may be considered for selected refractory cases of chronic postherniorrhaphy inguinal pain (CPIP). There is to date a paucity of easily applicable clinical tools to identify neuropathic pain and examine the neurosensory effects of remedial surgery. The present quantitative sensory testing (QST) pilot study evaluates a sensory mapping technique. Longitudinal (preoperative, immediate postoperative, and late postoperative) dermatomal sensory mapping and a comprehensive QST protocol were conducted in CPIP patients with unilateral, predominantly neuropathic inguinodynia presenting for triple neurectomy (n = 13). QST was conducted in four areas on the affected, painful side and in one contralateral comparison site. QST variables were compared according to sensory mapping outcomes: (o)/normal sensation, (+)/pain, and (-)/numbness. Diagnostic ability of the sensory mapping outcomes to detect QST-assessed allodynia or hypoesthesia was estimated through calculation of specificity and sensitivity values. Preoperatively, patients exhibited mechanical hypoesthesia and allodynia and pressure allodynia and hyperalgesia in painful areas mapped (+) (p < .05); sensory mapping outcome (+) demonstrated high ability to detect mechanical allodynia [sensitivity 0.74 (95% CI 0.61-0.86), specificity 0.94 (0.84-1.00)] and pressure allodynia [sensitivity 0.96 (0.89-1.00), specificity 1.00 (1.00-1.00)], but not thermal allodynia. Postoperatively, mapped areas of numbness (-) were associated with mechanical and thermal hypoesthesia (p < .05); (-) showed high sensitivity and specificity to detect mechanical and cold hypoesthesia. Sensory mapping provides an accurate clinical neuropathic assessment with strong correlation to QST findings of preoperative mechanical and pressure allodynia, and postoperative mechanical and thermal hypoesthesia in CPIP patients undergoing neurectomy.

Association of Chronic Pelvic Pain and Endometriosis With Signs of Sensitization and Myofascial Pain

PubMed Central

Stratton, Pamela; Khachikyan, Izabella; Sinaii, Ninet; Ortiz, Robin; Shah, Jay

2014-01-01

Objective To evaluate sensitization, myofascial trigger points, and quality of life in women with chronic pelvic pain with and without endometriosis. Methods A cross-sectional prospective study of women aged 18 to 50 with pain suggestive of endometriosis and healthy, pain-free volunteers without history of endometriosis. Patients underwent a physiatric neuro-musculoskeletal assessment of clinical signs of sensitization and myofascial trigger points in the abdominopelvic region. Pain symptoms, psychosocial, and quality-of-life measures were also assessed. All pain participants underwent laparoscopic excision of suspicious lesions to confirm endometriosis diagnosis by histologic evaluation. Results Patients included 18 with current, biopsy-proven endometriosis, 11 with pain only, and 20 healthy volunteers. The prevalence of sensitization as measured by regional allodynia and hyperalgesia was similar in both pain groups (83% and 82%) but much lower among healthy volunteers (15%, p<0.001). Nearly all women with pain had myofascial trigger points (94% and 91%). Adjusting for study group, those with high anxiety (OR=1.05, 95% CI:1.004–1.099; p=0.031) and depression (OR=1.06, 95% CI:1.005–1.113; p=0.032) scores were more likely to have sensitization. Pain patients with any history of endometriosis had the highest proportion of sensitization compared to the others (87% v 67% v 15%; p<0.001). Adjusting for any history of endometriosis, those with myofascial trigger points were most likely sensitized (OR=9.41, 95% CI:1.77–50.08, p=0.009). Conclusions Sensitization and myofascial trigger points were common in women with pain regardless of whether they had endometriosis at surgery. Those with any history of endometriosis were most likely to have sensitization. Traditional methods of classifying endometriosis-associated pain based on disease, duration, and anatomy are inadequate and should be replaced by a mechanism-based evaluation, as our study illustrates. PMID:25730237

Does catastrophic thinking enhance oesophageal pain sensitivity? An experimental investigation.

PubMed

Martel, M O; Olesen, A E; Jørgensen, D; Nielsen, L M; Brock, C; Edwards, R R; Drewes, A M

2016-09-01

Gastro-oesophageal reflux disease (GORD) is a major health problem that is frequently accompanied by debilitating oesophageal pain symptoms. The first objective of the study was to examine the association between catastrophizing and oesophageal pain sensitivity. The second objective was to examine whether catastrophizing was associated with the magnitude of acid-induced oesophageal sensitization. Twenty-five healthy volunteers (median age: 24.0 years; range: 22-31) were recruited and were asked to complete the Pain Catastrophizing Scale (PCS). During two subsequent study visits, mechanical, thermal, and electrical pain sensitivity in the oesophagus was assessed before and after inducing oesophageal sensitization using a 30-min intraluminal oesophageal acid perfusion procedure. Analyses were conducted based on data averaged across the two study visits. At baseline, catastrophizing was significantly associated with mechanical (r = -0.42, p < 0.05) and electrical (r = -0.60, p < 0.01) pain thresholds. After acid perfusion, catastrophizing was also significantly associated with mechanical (r = -0.58, p < 0.01) and electrical (r = -0.50, p < 0.05) pain thresholds. Catastrophizing was not significantly associated with thermal pain thresholds. Subsequent analyses revealed that catastrophizing was not significantly associated with the magnitude of acid-induced oesophageal sensitization. Taken together, findings from the present study suggest that catastrophic thinking exerts an influence on oesophageal pain sensitivity, but not necessarily on the magnitude of acid-induced oesophageal sensitization. WHAT DOES THIS STUDY ADD?: Catastrophizing is associated with heightened pain sensitivity in the oesophagus. This was substantiated by assessing responses to noxious stimulation of the oesophagus using an experimental paradigm mimicking features and symptoms experienced by patients with gastro-oesophageal reflux disease (GORD). © 2016 European Pain Federation - EFIC®

Development of Short-Form Versions of the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R): A Proof-of-Principle Study.

PubMed

Finkelman, Matthew D; Smits, Niels; Kulich, Ronald J; Zacharoff, Kevin L; Magnuson, Britta E; Chang, Hong; Dong, Jinghui; Butler, Stephen F

2017-07-01

The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item questionnaire designed to assess risk of aberrant medication-related behaviors in chronic pain patients. The introduction of short forms of the SOAPP-R may save time and increase utilization by practitioners. To develop and evaluate candidate SOAPP-R short forms. Retrospective study. Pain centers. Four hundred and twenty-eight patients with chronic noncancer pain. Subjects had previously been administered the full-length version of the SOAPP-R and been categorized as positive or negative for aberrant medication-related behaviors via the Aberrant Drug Behavior Index (ADBI). Short forms of the SOAPP-R were developed using lasso logistic regression. Sensitivity, specificity, and area under the curve (AUC) of all forms were calculated with respect to the ADBI using the complete data set, training-test analysis, and 10-fold cross-validation. The coefficient alpha of each form was also calculated. An external set of 12 pain practitioners reviewed the forms for content. In the complete data set analysis, a form of 12 items exhibited sensitivity, specificity, and AUC greater than or equal to those of the full-length SOAPP-R (which were 0.74, 0.67, and 0.76, respectively). The short form had a coefficient alpha of 0.76. In the training-test analysis and 10-fold cross-validation, it exhibited an AUC value within 0.01 of that of the full-length SOAPP-R. The majority of external practitioners reported a preference for this short form. The 12-item version of the SOAPP-R has potential as a short risk screener and should be tested prospectively. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Neonatal Sleep Restriction Increases Nociceptive Sensitivity in Adolescent Mice.

PubMed

Araujo, Paula; Coelho, Cesar A; Oliveira, Maria G; Tufik, Sergio; Andersen, Monica L

2018-03-01

Sleep loss in infants may have a negative effect on the functional and structural development of the nociceptive system. We tested the hypothesis that neonatal sleep restriction induces a long-term increase of pain-related behaviors in mice and that this hypersensitivity occurs due to changes in the neuronal activity of nociceptive pathways. We aim to investigate the effects of sleep loss in neonatal mice on pain behaviors of adolescent and adult mice in a sex-dependent manner. We also analyzed neuroanatomical and functional changes in pain pathways associated with behavioral changes. An experimental animal study. A basic sleep research laboratory at Universidade Federal de São Paulo in Brazil. Neonatal mice at postnatal day (PND) 12 were randomly assigned to either control (CTRL), maternal separation (MS), or sleep restriction (SR) groups. MS and SR were performed 2 hours a day for 10 days (PND 12 until PND 21). The gentle handling method was used to prevent sleep. At PND 21, PND 35, or PND 90, the mice were tested for pain-related behaviors. Their brains were harvested and immunohistochemically stained for c-Fos protein in the anterior cingulate cortex, primary somatosensory cortex, and periaqueductal gray (PAG). Neonatal SR significantly increased nociceptive sensitivity in the hot plate test in adolescent mice (-23.5% of pain threshold). This alteration in nociceptive response was accompanied by a decrease in c-Fos expression in PAG (-40% of c-Fos positive cells compared to the CTRL group). The hypersensitivity found in adolescent mice was not present in adult animals, and all mice showed a comparable nociceptive response. Even using a mild manipulation method, in which a minimal amount of handling was applied to maintain wakefulness, sleep deprivation was a stressful event evidenced by higher corticosterone levels. Repeated exposures to sleep loss during early life were able to induce changes in the nociceptive response associated with alterations in neural activity in descending control of pain. Brain maturation, hypersensitivity, neuronal activity, nociception, pain, periaqueductal gray, postnatal development, sleep, sleep deprivation.

Hypnosis as sole anaesthesia for skin tumour removal in a patient with multiple chemical sensitivity.

PubMed

Facco, E; Pasquali, S; Zanette, G; Casiglia, E

2013-09-01

A female patient with multiple chemical sensitivity and previous anaphylactoid reactions to local anaesthetics was admitted for removal of a thigh skin tumour under hypnosis as sole anaesthesia. The hypnotic protocol included hypnotic focused analgesia and a pre-operative pain threshold test. After inducing hypnosis, a wide excision was performed, preserving the deep fascia, and the tumour was removed; the patient's heart rate and blood pressure did not increase during the procedure. When the patient was de-hypnotised, she reported no pain and was discharged immediately. Our case confirms the efficacy of hypnosis and demonstrates that it may be valuable as a sole anaesthetic method in selected cases. Hypnosis can prevent pain perception and surgical stress as a whole, comparing well with anaesthetic drugs. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy

PubMed Central

Campbell, Claudia M.; Kipnes, Mark S.; Stouch, Bruce C.; Brady, Kerrie L.; Kelly, Margaret; Schmidt, William K.; Petersen, Karin L.; Rowbotham, Michael C.; Campbell, James N.

2012-01-01

A length-dependent neuropathy with pain in the feet is a common complication of diabetes (painful diabetic neuropathy, PDN). It was hypothesized that pain may arise from sensitized-hyperactive cutaneous nociceptors, and that this abnormal signaling may be reduced by topical administration of the α2-adrenergic agonist, clonidine, to the painful area. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-center trial. Nociceptor function was measured by determining the painfulness of 0.1% topical capsaicin applied to the pre-tibial area of each subject for 30 minutes during screening. Subjects were then randomized to receive 0.1% topical clonidine gel (n=89) or placebo gel (n=90) applied t.i.d. to their feet for 12 weeks. The difference in foot pain at week 12 in relation to baseline, rated on a 0-10 numerical pain rating scale (NPRS), was compared between groups. Baseline NPRS was imputed for missing data for subjects who terminated the study early. The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo-treated group (the primary endpoint; p=0.07). In subjects who felt any level of pain to capsaicin, clonidine was superior to placebo (p<0.05). In subjects with a capsaicin pain rating ≥2 (0-10, NPRS), the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo (p=0.01). Topical clonidine gel significantly reduces the level of foot pain in PDN subjects with functional (and possibly sensitized) nociceptors in the affected skin as revealed by testing with topical capsaicin. Screening for cutaneous nociceptor function may help distinguish candidates for topical therapy for neuropathic pain. PMID:22683276

The impact of extended electrodiagnostic studies in Ulnar Neuropathy at the elbow

PubMed Central

Todnem, Kari; Michler, Ralf Peter; Wader, Tony Eugen; Engstrøm, Morten; Sand, Trond

2009-01-01

Background This study aimed to explore the value of extended motor nerve conduction studies in patients with ulnar nerve entrapment at the elbow (UNE) in order to find the most sensitive and least time-consuming method. We wanted to evaluate the utility of examining both the sensory branch from the fifth finger and the dorsal branch of the ulnar nerve. Further we intended to study the clinical symptoms and findings, and a possible correlation between the neurophysiological findings and pain. Methods The study was prospective, and 127 UNE patients who were selected consecutively from the list of patients, had a clinical and electrodiagnostic examination. Data from the most symptomatic arm were analysed and compared to the department's reference limits. Student's t - test, chi-square tests and multiple regression models were used. Two-side p-values < 0.05 were considered as significant. Results Ulnar paresthesias (96%) were more common than pain (60%). Reduced ulnar sensitivity (86%) and muscle strength (48%) were the most common clinical findings. Adding a third stimulation site in the elbow mid-sulcus for motor conduction velocity (MCV) to abductor digiti minimi (ADM) increased the electrodiagnostic sensitivity from 80% to 96%. Additional recording of ulnar MCV to the first dorsal interosseus muscle (FDI) increased the sensitivity from 96% to 98%. The ulnar fifth finger and dorsal branch sensory studies were abnormal in 39% and 30% of patients, respectively. Abnormal electromyography in FDI was found in 49% of the patients. Patients with and without pain had generally similar conduction velocity parameter means. Conclusion We recommend three stimulation sites at the elbow for MCV to ADM. Recording from FDI is not routinely indicated. Sensory studies and electromyography do not contribute much to the sensitivity of the electrodiagnostic evaluation, but they are useful to document axonal degeneration. Most conduction parameters are unrelated to the presence of pain. PMID:19814833

Cold Pressor Pain Sensitivity in Twins Discordant for Chronic Fatigue Syndrome

PubMed Central

Ullrich, Phil; Afari, Niloofar; Jacobsen, Clemma; Goldberg, Jack; Buchwald, Dedra

2010-01-01

Objective Individuals with chronic fatigue syndrome (CFS) experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their cotwins without CFS. Design Cotwin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS. Patients and Setting Fifteen twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington. Results Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their cotwins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain (p = 0.003) and fatigue (p < 0.001) by their cotwins without CFS. Conclusions These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS. PMID:17371408

Ethnicity is associated with alterations in oxytocin relationships to pain sensitivity in women

PubMed Central

Grewen, Karen M.; Light, Kathleen C.; Mechlin, Beth; Girdler, Susan S.

2015-01-01

It is well established that African Americans (AA) experience greater pain associated with a variety of clinical conditions, and greater pain sensitivity to experimental pain tasks relative to non-Hispanic Whites (W). Notably, African Americans do not show the same relationships involving endogenous pain regulatory mechanisms and pain sensitivity documented in Caucasians, including positive associations between blood pressure, norepinephrine, cortisol and greater pain tolerance. Objectives The purpose of this study was to examine the relationship between plasma oxytocin (OT) and pain sensitivity and to explore the relation of OT to other factors known to influence pain perception. Design OT concentration and sensitivity to ischemic, cold pressor, and thermal pain tasks were assessed in African American (n=25) and non-Hispanic White (n=23) pre-menopausal women. Results African American women demonstrated significantly lower pain tolerance across tasks compared with Whites (F1,46 =6.31, p=0.0156) and also exhibited lower plasma OT levels (AA: 3.90, W: 7.05 pg/mL; p=0.0014). Greater OT levels were correlated with greater tolerance to ischemic pain (r=0.36, p=0.013) and accounted for a marginally significant portion of the ethnic difference in ischemic pain tolerance (B=+0.29, p=0.06). Greater OT was also correlated with greater tolerance of cold pressor pain (r=0.31, p=0.03); however, this association was no longer seen after the variance due to ethnicity was accounted for. Conclusion These data suggest that reduced oxytocinergic function may be one of multiple biological factors contributing to the greater sensitivity to experimental ischemic pain, and to the greater burden of some types of clinical pain experienced by African Americans compared with Whites. PMID:18568974

Point-of-care heart-type fatty acid binding protein versus high-sensitivity troponin T testing in emergency patients at high risk for acute coronary syndrome.

PubMed

Kellens, Sebastiaan; Verbrugge, Frederik H; Vanmechelen, Maxime; Grieten, Lars; Van Lierde, Johan; Dens, Joseph; Vrolix, Mathias; Vandervoort, Pieter

2016-04-01

High-sensitivity cardiac troponin testing is used to detect myocardial damage in patients with acute chest pain. Heart-type fatty acid binding protein (H-FABP) may be an alternative, available as point-of-care test. Patients (n=203) referred by general practitioners for suspected acute coronary syndrome or presenting with typical chest pain and one major cardiovascular risk factor at the emergency department were prospectively included in a single-centre cohort study. High-sensitivity cardiac troponin T (hs-TnT) and point-of-care H-FABP testing were concomitantly performed at admission and after 6h. Maximal hs-TnT levels above the 99th percentile were observed in 152 patients (75%) with 127 (63%) fulfilling criteria for myocardial infarction. Upon admission, hs-TnT and H-FABP were associated with an area under the curve (95% CI) of 0.83 (0.77-0.89) and 0.79 (0.73-0.85), respectively, to predict myocardial infarction, which increased to 0.93 (0.90-0.97) and 0.88 (0.84-0.93), respectively, after 6h. The diagnostic accuracy for non-ST-segment elevation myocardial infarction was somewhat lower with an area under the curve (95% CI) of 0.80 (0.72-0.87), 0.90 (0.84-0.96), 0.73 (0.64-0.81) and 0.77 (0.67-0.86), respectively. When assessment was performed within 3h of chest pain onset, diagnostic accuracy of H-FABP versus hs-TnT was similar. Each standard deviation increase in admission H-FABP was associated with a 68% relative risk increase of all-cause mortality (p-value=0.027) during 666 ± 155 days of follow-up. Point-of-care H-FABP testing has lower diagnostic accuracy compared with hs-TnT assessment in patients with high pre-test acute coronary syndrome probability, but might be of interest when assessment is possible early after chest pain onset. © The European Society of Cardiology 2015.

Subjective Sleep Quality Deteriorates Prior to Development of Painful Temporomandibular Disorder

PubMed Central

Sanders, Anne E.; Akinkugbe, Aderonke A.; Bair, Eric; Fillingim, Roger B.; Greenspan, Joel D.; Ohrbach, Richard; Dubner, Ronald; Maixner, William; Slade, Gary D.

2016-01-01

There is good evidence that poor sleep quality increases risk of painful temporomandibular disorder (TMD). However little is known about the course of sleep quality in the months preceding TMD onset, and whether the relationship is mediated by heightened sensitivity to pain. The Pittsburgh Sleep Quality Index was administered at enrollment into the OPPERA prospective cohort study. Thereafter the Sleep Quality Numeric Rating Scale was administered every three months to 2,453 participants. Sensitivity to experimental pressure pain and pinprick pain stimuli was measured at baseline and repeated during follow-up of incident TMD cases (n=220) and matched TMD-free controls (n=193). Subjective sleep quality deteriorated progressively, but only in those who subsequently developed TMD. A Cox proportional hazards model showed that risk of TMD was greater among participants whose sleep quality worsened during follow-up (adjusted hazard ratio=1.73, 95% confidence limits: 1.29, 2.32). This association was independent of baseline measures of sleep quality, psychological stress, somatic awareness, comorbid conditions, non-pain facial symptoms and demographics. Poor baseline sleep quality was not significantly associated with baseline pain sensitivity or with subsequent change in pain sensitivity. Furthermore the relationship between sleep quality and TMD incidence was not mediated via baseline pain sensitivity nor change in pain sensitivity. PMID:26902644

Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer disease compared to healthy control subjects.

PubMed

Jensen-Dahm, Christina; Werner, Mads U; Dahl, Jørgen B; Jensen, Troels Staehelin; Ballegaard, Martin; Hejl, Anne-Mette; Waldemar, Gunhild

2014-08-01

Patients with Alzheimer disease (AD) report pain less frequently than their cognitively intact peers. It has been hypothesized that pain processing is altered in AD. The aim of this study was to investigate agreement and reliability of 3 pain sensitivity tests and to examine pain threshold and tolerance in patients with AD. We examined 29 patients with mild to moderate AD and 29 age- and gender-matched healthy control subjects with quantitative sensory testing, ie, assessments of detection threshold (warmth detection threshold [WDT]) and pain threshold (heat pain threshold [HPT], pressure algometry, cold pressor test), and assessments of tolerance (pressure algometry, cold pressor test). All procedures were done twice on day 1, 1 hour apart, and repeated on day 2. We found no difference between groups for WDT (patient vs control subjects: mean [95% confidence interval]: 35.5°C [33.4°C to 37.6°C] vs 35.4°C [34.3°C to 36.5°C], P=.8) or HPT (41.2°C [40.0°C to 42.4°C] vs 42.3°C [41.1°C to 43.5°C], P=.24). We observed comparable thresholds for pressure algometry (median [25% to 75% interquartile range]: 120 kPa [100 to 142 kPa] vs 131 kPa [113 to 192 kPa], P=.10), but significantly lower tolerance in AD patients (213 kPa [188 to 306 kPa] vs 289 kPa [262 to 360 kPa], P=.008). No differences were found for the cold pressor test. The study demonstrated good replicability of the sensory testing data with comparable data variability, for both groups, which supports the use of these methods in studies of patients with mild to moderate AD. Contrary to previous studies, we observed a reduced pain tolerance in patients with mild to moderate AD, which suggests that the reduced report of pain cannot be explained by reduced processing of painful stimuli. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Relative and absolute test-retest reliabilities of pressure pain threshold in patients with knee osteoarthritis.

PubMed

Srimurugan Pratheep, Neeraja; Madeleine, Pascal; Arendt-Nielsen, Lars

2018-04-25

Pressure pain threshold (PPT) and PPT maps are commonly used to quantify and visualize mechanical pain sensitivity. Although PPT's have frequently been reported from patients with knee osteoarthritis (KOA), the absolute and relative reliability of PPT assessments remain to be determined. Thus, the purpose of this study was to evaluate the test-retest relative and absolute reliability of PPT in KOA. For that purpose, intra- and interclass correlation coefficient (ICC) as well as the standard error of measurement (SEM) and the minimal detectable change (MDC) values within eight anatomical locations covering the most painful knee of KOA patients was measured. Twenty KOA patients participated in two sessions with a period of 2 weeks±3 days apart. PPT's were assessed over eight anatomical locations covering the knee and two remote locations over tibialis anterior and brachioradialis. The patients rated their maximum pain intensity during the past 24 h and prior to the recordings on a visual analog scale (VAS), and completed The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and PainDetect surveys. The ICC, SEM and MDC between the sessions were assessed. The ICC for the individual variability was expressed with coefficient of variance (CV). Bland-Altman plots were used to assess potential bias in the dataset. The ICC ranged from 0.85 to 0.96 for all the anatomical locations which is considered "almost perfect". CV was lowest in session 1 and ranged from 44.2 to 57.6%. SEM for comparison ranged between 34 and 71 kPa and MDC ranged between 93 and 197 kPa with a mean PPT ranged from 273.5 to 367.7 kPa in session 1 and 268.1-331.3 kPa in session 2. The analysis of Bland-Altman plot showed no systematic bias. PPT maps showed that the patients had lower thresholds in session 2, but no significant difference was observed for the comparison between the sessions for PPT or VAS. No correlations were seen between PainDetect and PPT and PainDetect and WOMAC. Almost perfect relative and absolute reliabilities were found for the assessment of PPT's for KOA patients. The present investigation implicates that PPT's is reliable for assessing pain sensitivity and sensitization in KOA patients.

Operant conditioning of enhanced pain sensitivity by heat-pain titration.

PubMed

Becker, Susanne; Kleinböhl, Dieter; Klossika, Iris; Hölzl, Rupert

2008-11-15

Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.

Blood pressure and pain sensitivity in children and adolescents.

PubMed

Drouin, Sammantha; McGrath, Jennifer J

2013-06-01

Elevated blood pressure is associated with diminished pain sensitivity. While this finding is well established in adults, it is less clear when the relation between blood pressure and pain sensitivity emerges across the life course. Evidence suggests this phenomenon may exist during childhood. Children (N = 309; 56% boys) aged 10-15 years and their parents participated. Blood pressure readings were taken during a resting baseline. Maximum pain intensity was rated using a visual analogue scale (rated 0-10) in response to a finger prick pain induction. Parent-measured resting blood pressure was inversely associated with boys' pain ratings only. Cross-sectionally, lower pain ratings were related to higher SBP, univariately. Longitudinally, pain ratings predicted higher DBP, even after controlling for covariates. Determining when and how the relation between blood pressure and pain sensitivity emerges may elucidate the pathophysiology of hypertension. Copyright © 2013 Society for Psychophysiological Research.

Protecting Pain Patients. The Evaluation of a Chronic Pain Educational Intervention.

PubMed

Holliday, Simon; Hayes, Chris; Dunlop, Adrian; Morgan, Simon; Tapley, Amanda; Henderson, Kim; Larance, Briony; Magin, Parker

2017-12-01

Advocacy and commercially funded education successfully reduced barriers to the provision of long-term opioid analgesia. The subsequent escalation of opioid prescribing for chronic noncancer pain has seen increasing harms without improved pain outcomes. This was a one-group pretest-posttest design study. A multidisciplinary team developed a chronic pain educational package for general practitioner trainees emphasizing limitations, risk-mitigation, and deprescribing of opioids with transition to active self-care. This educational intervention incorporated prereadings, a resource kit, and a 90-minute interactional video case-based workshop incorporated into an education day. Evaluation was via pre- and postintervention (two months) questionnaires. Differences in management of two clinical vignettes were tested using McNemar's test. Of 58 eligible trainees, 47 (response rate = 81.0%) completed both questionnaires (36 of whom attended the workshop). In a primary analysis including these 47 trainees, therapeutic intentions of tapering opioid maintenance for pain (in a paper-based clinical vignette) increased from 37 (80.4%) pre-intervention to 44 (95.7%) postintervention (P = 0.039). In a sensitivity analysis including only trainees attending the workshop, 80.0% pre-intervention and 97.1% postintervention tapered opioids (P = 0.070). Anticipated initiation of any opioids for a chronic osteoarthritic knee pain clinical vignette reduced from 35 (74.5%) to 24 (51.1%; P = 0.012) in the primary analysis and from 80.0% to 41.7% in the sensitivity analysis (P = 0.001). Necessary improvements in pain management and opioid harm avoidance are predicated on primary care education being of demonstrable efficacy. This brief educational intervention improved hypothetical management approaches two months subsequently. Further research measuring objective changes in physician behavior, especially opioid prescribing, is indicated. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Testing the link between sympathetic efferent and sensory afferent fibers in neuropathic pain

PubMed Central

Raja, Srinivasa N.; Treede, Rolf-Detlef

2012-01-01

The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic alpha-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done in random order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P greater than 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that alpha-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP. PMID:22592181

Relationships between the intensity and duration of Peltier heat stimulation and pain magnitude

PubMed Central

Vierck, Charles J.; Mauderli, Andre P.; Riley, Joseph L.

2013-01-01

Ramp-and-hold heat stimulation with a Peltier thermode is a standard procedure for quantitative sensory testing of human pain sensitivity. Because myelinated and unmyelinated nociceptive afferents respond preferentially to changing and steady temperatures, respectively, ramp-and-hold heat stimulation could assess processing of input from A-delta nociceptors early and C nociceptors late during prolonged thermal stimulation. In order to evaluate the progression from dynamic change to a steady temperature during prolonged Peltier stimulation, recordings of temperatures at the probe-skin interface were obtained. First, recordings of temperature during contact-and-hold stimulation (solenoid powered delivery of a preheated thermode to the skin) provided an evaluation of heat dissipation from the beginning of stimulation, uncontaminated by ramping. The heat sink effect lasted up to 8 sec. and accounted in part for substantial increases in pain intensity as a combined function of durations from 1–16 sec. and stimulus intensities from 43°C to 59°. Recordings during longer periods of stimulation showed that Peltier stimulation generated feedback oscillations in temperature for up to 75 sec that were tracked by subjects’ continuous ratings of pain. During 120 sec. trials, sensitization of pain was observed over 45 seconds after the oscillations subsided. In contrast, sensitization was not observed during 130.5 sec. of stimulation with alternately increasing and decreasing temperatures that maintained a target eVAS rating of 35. Thus, long duration stimulation can be utilized to evaluate sensitization, presumably of C nociception, when not disrupted by oscillations inherent to feedback control of Peltier stimulation. PMID:23423165

Relationships between the intensity and duration of Peltier heat stimulation and pain magnitude.

PubMed

Vierck, Charles J; Mauderli, Andre P; Riley, Joseph L

2013-03-01

Ramp-and-hold heat stimulation with a Peltier thermode is a standard procedure for quantitative sensory testing of human pain sensitivity. Because myelinated and unmyelinated nociceptive afferents respond preferentially to changing and steady temperatures, respectively, ramp-and-hold heat stimulation could assess processing of input from A-delta nociceptors early and C nociceptors late during prolonged thermal stimulation. In order to evaluate the progression from dynamic change to a steady temperature during prolonged Peltier stimulation, recordings of temperatures at the probe-skin interface were obtained. First, recordings of temperature during contact-and-hold stimulation (solenoid powered delivery of a preheated thermode to the skin) provided an evaluation of heat dissipation from the beginning of stimulation, uncontaminated by ramping. The heat-sink effect lasted up to 8 s and accounted in part for a slow increase in pain intensity for stimulus durations of 1-16 s and stimulus intensities of 43-59 °C. Recordings during longer periods of stimulation showed that feedback-controlled Peltier stimulation generated oscillations in temperature that were tracked for up to 75 s by subjects' continuous ratings of pain. During 120-s trials, sensitization of pain was observed over 45 s after the oscillations subsided. Thus, long-duration stimulation can be utilized to evaluate sensitization, presumably of C nociception, when not disrupted by oscillations in thermode temperature (e.g., those inherent to feedback control of Peltier stimulation). In contrast, sensitization was not observed during 130.5 s of stimulation with alternately increasing and decreasing temperatures that repeatedly activated A-delta nociceptors.

Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons.

PubMed

Weissman-Fogel, Irit; Sprecher, Elliot; Granovsky, Yelena; Yarnitsky, David

2003-08-01

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.

Interactions among sex, ethnicity, religion, and gender role expectations of pain.

PubMed

Defrin, Ruth; Eli, Ilana; Pud, Dorit

2011-06-01

Sex, gender, ethnicity, and religion are powerful factors that may affect pain experience. Recently, gender role expectations of pain (GREP) were suggested to account for some of the differences in pain perception between men and women. However, the interaction between GREP and ethnicity and religion was not examined. This interaction was studied with regard to pain sensitivity, pain endurance, and willingness to report pain. Our objective was to study the interaction among GREP, sex, and ethno-religious belonging. Participants (548 healthy men and women) of 3 different ethno-religious groups (341 Jews, 105 Muslim-Arabs, 102 Christian-Arabs) completed the GREP questionnaire; pain sensitivity, pain endurance, and willingness to report pain were analyzed. Men of all 3 ethno-religious groups perceived themselves and other men as less sensitive and less willing to report pain than typical women. Women of all 3 ethno-religious groups perceived themselves and other women as more sensitive and more willing to report pain than men. Ethno-religious differences were observed in the attitudes towards typical men and women, with Christian men and women exhibiting stronger stereotypical views regarding pain sensitivity and pain endurance. Individual's perceptions of pain regarding one's self compared with the same or opposite sex were similar regardless of ethno-religious belonging and were related to sex. However, attitudes on pain of typical men and women seemed to be influenced by ethno-religious belonging. This differential effect of ethno-religion on GREP with relation to sex suggests that these factors should be considered when pain perception is evaluated. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

The clinical impact of a false-positive urine cocaine screening result on a patient's pain management.

PubMed

Kim, James A; Ptolemy, Adam S; Melanson, Stacy E F; Janfaza, David R; Ross, Edgar L

2015-06-01

The urine of a patient admitted for chest and epigastric pain tested positive for cocaine using an immunoassay-based drug screening method (positive/negative cutoff concentration 150 ng/mL). Despite the patient's denial of recent cocaine use, this positive cocaine screening result in conjunction with a remote history of drug misuse impacted the patient's recommended pain therapy. Specifically, these factors prompted the clinical team to question the appropriateness of opioids and other potentially addictive therapeutics during the treatment of cancer pain from previously undetected advanced pancreatic carcinoma. After pain management and clinical pathology consultation, it was decided that the positive cocaine screening result should be confirmed by gas chromatography-mass spectrometry (GC-MS) testing. This more sensitive and specific analytical technique revealed that both cocaine and its primary metabolite benzoylecgonine were undetectable (i.e., less than the assay detection limit of 50 ng/mL), thus indicating that the positive urine screening result was falsely positive. With this confirmation, the pain management service team was reassured in offering intrathecal pump (ITP) therapy for pain control. ITP implantation was well tolerated, and the patient eventually achieved excellent pain relief. However, ITP therapy most likely would not have been utilized without the GC-MS confirmation testing unless alternative options failed and extensive vigilant monitoring was initiated. As exemplified in this case, confirmatory drug testing should be performed on specimens with unexpected immunoassay-based drug screening results. To our knowledge, this is the first report of a false-positive urine cocaine screening result and its impact on patient management. Wiley Periodicals, Inc.

Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain

PubMed Central

Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

2005-01-01

Aims Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. Methods The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (°C), as well as suprathreshold tonic heat pain intensity (46.5 °C for 1 min) measured by 0–10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. Results No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI −8.8, 42.8), P = 0.19), pressure (2.2 mmHg (−28.7, 33.2), P = 0.89) and heat (−0.3 °C (−1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities −0.4 NPS units (95% CI −1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the ‘weak’ opioid-treated subgroup and the ‘strong’ opioid-treated subgroup again revealed insignificant results. Conclusions These results suggest that the administration of ‘commonly used’ dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients receiving non-opioid analgesia. PMID:16120071

γ-Aminobutyric acid (GABA) oral rinse reduces capsaicin-induced burning mouth pain sensation: An experimental quantitative sensory testing study in healthy subjects.

PubMed

Zhang, Y; Wang, K; Arendt-Nielsen, L; Cairns, B E

2018-02-01

In burning mouth patients, analgesia after oral administration of clonazepam may result from modulation of peripheral γ-aminobutyric acid (GABA) receptors. The effect of oral administration of test solutions (water, 0.5 mol/L or 0.05 mol/L GABA, 1% lidocaine) was investigated for the amelioration of pain and sensitivity induced by application of capsaicin (1%, 2 min) to the tongue of thirty healthy male and female subjects in this four-session, randomized, placebo-controlled, double-blinded, cross-over study. Intra-oral quantitative sensory testing was used to assess cold (CDT), warm (WDT) and mechanical (MDT) detection thresholds as well as mechanical (MPT) and heat (HPT) pain thresholds. Capsaicin-induced pain intensity was continuously rated on a 0-10 electronic visual analogue scale (VAS). The area under the VAS curve (VASAUC) after rinsing was calculated for each solution. Capsaicin application on the tongue evoked burning pain with a peak of 4.8/10, and significantly increased CDT and MDT while significantly decreasing WDT, HPT, and MPT. The VASAUC was significantly smaller after oral rinse with 0.05 mol/L GABA, 0.5 mol/L GABA, and 1% lidocaine than after oral rinse with water. Rinse with 0.5 mol/L or 0.05 mol/L GABA were similarly effective in decreasing VASAUC. Rinsing with either 1% lidocaine, 0.5 mol/L or 0.05 mol/L GABA also significantly attenuated the effects of capsaicin on WDT and HPT in a treatment independent manner. There were no sex-related differences in these effects of GABA. Capsaicin-induced burning tongue pain and decreases in WDT and HPT can be ameliorated by rinsing the mouth with lidocaine and GABA solutions. Rinsing the mouth with an oral GABA containing solution ameliorated burning pain and increased heat sensitivity produced by application of capsaicin to the tongue. This finding suggests that GABA can act as a local analgesic agent in the oral cavity. © 2017 European Pain Federation - EFIC®.

Mechanistic experimental pain assessment in computer users with and without chronic musculoskeletal pain.

PubMed

Ge, Hong-You; Vangsgaard, Steffen; Omland, Øyvind; Madeleine, Pascal; Arendt-Nielsen, Lars

2014-12-06

Musculoskeletal pain from the upper extremity and shoulder region is commonly reported by computer users. However, the functional status of central pain mechanisms, i.e., central sensitization and conditioned pain modulation (CPM), has not been investigated in this population. The aim was to evaluate sensitization and CPM in computer users with and without chronic musculoskeletal pain. Pressure pain threshold (PPT) mapping in the neck-shoulder (15 points) and the elbow (12 points) was assessed together with PPT measurement at mid-point in the tibialis anterior (TA) muscle among 47 computer users with chronic pain in the upper extremity and/or neck-shoulder pain (pain group) and 17 pain-free computer users (control group). Induced pain intensities and profiles over time were recorded using a 0-10 cm electronic visual analogue scale (VAS) in response to different levels of pressure stimuli on the forearm with a new technique of dynamic pressure algometry. The efficiency of CPM was assessed using cuff-induced pain as conditioning pain stimulus and PPT at TA as test stimulus. The demographics, job seniority and number of working hours/week using a computer were similar between groups. The PPTs measured at all 15 points in the neck-shoulder region were not significantly different between groups. There were no significant differences between groups neither in PPTs nor pain intensity induced by dynamic pressure algometry. No significant difference in PPT was observed in TA between groups. During CPM, a significant increase in PPT at TA was observed in both groups (P < 0.05) without significant differences between groups. For the chronic pain group, higher clinical pain intensity, lower PPT values from the neck-shoulder and higher pain intensity evoked by the roller were all correlated with less efficient descending pain modulation (P < 0.05). This suggests that the excitability of the central pain system is normal in a large group of computer users with low pain intensity chronic upper extremity and/or neck-shoulder pain and that increased excitability of the pain system cannot explain the reported pain. However, computer users with higher pain intensity and lower PPTs were found to have decreased efficiency in descending pain modulation.

A novel paradigm to evaluate conditioned pain modulation in fibromyalgia.

PubMed

Schoen, Cynthia J; Ablin, Jacob N; Ichesco, Eric; Bhavsar, Rupal J; Kochlefl, Laura; Harris, Richard E; Clauw, Daniel J; Gracely, Richard H; Harte, Steven E

2016-01-01

Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus. Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus. In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning ( P =0.007 and P =0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect ( P >0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation ( P =0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus ( P =0.269). The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls.

A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

PubMed Central

Schoen, Cynthia J; Ablin, Jacob N; Ichesco, Eric; Bhavsar, Rupal J; Kochlefl, Laura; Harris, Richard E; Clauw, Daniel J; Gracely, Richard H; Harte, Steven E

2016-01-01

Introduction Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus. Methods Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus. Results In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect (P>0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation (P=0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus (P=0.269). Conclusion The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls. PMID:27713648

Economic evaluation in chronic pain: a systematic review and de novo flexible economic model.

PubMed

Sullivan, W; Hirst, M; Beard, S; Gladwell, D; Fagnani, F; López Bastida, J; Phillips, C; Dunlop, W C N

2016-07-01

There is unmet need in patients suffering from chronic pain, yet innovation may be impeded by the difficulty of justifying economic value in a field beset by data limitations and methodological variability. A systematic review was conducted to identify and summarise the key areas of variability and limitations in modelling approaches in the economic evaluation of treatments for chronic pain. The results of the literature review were then used to support the development of a fully flexible open-source economic model structure, designed to test structural and data assumptions and act as a reference for future modelling practice. The key model design themes identified from the systematic review included: time horizon; titration and stabilisation; number of treatment lines; choice/ordering of treatment; and the impact of parameter uncertainty (given reliance on expert opinion). Exploratory analyses using the model to compare a hypothetical novel therapy versus morphine as first-line treatments showed cost-effectiveness results to be sensitive to structural and data assumptions. Assumptions about the treatment pathway and choice of time horizon were key model drivers. Our results suggest structural model design and data assumptions may have driven previous cost-effectiveness results and ultimately decisions based on economic value. We therefore conclude that it is vital that future economic models in chronic pain are designed to be fully transparent and hope our open-source code is useful in order to aspire to a common approach to modelling pain that includes robust sensitivity analyses to test structural and parameter uncertainty.

Evaluation of acute knee pain in primary care.

PubMed

Jackson, Jeffrey L; O'Malley, Patrick G; Kroenke, Kurt

2003-10-07

The evaluation of acute knee pain often includes radiography of the knee. To synthesize the literature to determine the role of radiologic procedures in evaluating common causes of acute knee pain: fractures, meniscal or ligamentous injuries, osteoarthritis, and pseudogout. MEDLINE search from 1966 to October 2002. We included all published, peer-reviewed studies of decision rules for fractures. We included studies that used arthroscopy as the gold standard for measuring the accuracy of the physical examination and magnetic resonance imaging (MRI) for meniscal and ligamentous knee damage. We included all studies on the use of radiographs in pseudogout. We extracted all data in duplicate and abstracted physical examination and MRI results into 2 x 2 tables. Among the 5 decision rules for deciding when to use plain films in knee fractures, the Ottawa knee rules (injury due to trauma and age >55 years, tenderness at the head of the fibula or the patella, inability to bear weight for 4 steps, or inability to flex the knee to 90 degrees) have the strongest supporting evidence. When the history suggests a potential meniscal or ligamentous injury, the physical examination is moderately sensitive (meniscus, 87%; anterior cruciate ligament, 74%; and posterior cruciate ligament, 81%) and specific (meniscus, 92%; anterior cruciate ligament, 95%; and posterior cruciate ligament, 95%). The Lachman test is more sensitive and specific for ligamentous tears than is the drawer sign. For meniscal tears, joint line tenderness is sensitive (75%) but not specific (27%), while the McMurray test is specific (97%) but not sensitive (52%). Compared with the physical examination, MRI is more sensitive for ligamentous and meniscal damage but less specific. When the differential diagnosis for acute knee pain includes an exacerbation of osteoarthritis, clinical features (age >50 years, morning stiffness <30 minutes, crepitus, or bony enlargement) are 89% sensitive and 88% specific for underlying chronic arthritis. Adding plain films improves sensitivity slightly but not specificity. Plain films for pseudogout are not sensitive or specific, according to limited-quality studies. We recommend the Ottawa knee rules to decide when to obtain plain films for suspected knee fracture. A careful physical examination should be sufficient to decide whether to refer patients with potential meniscal and ligament injuries, and we prefer clinical criteria rather than plain films for evaluating osteoarthritis. We do not recommend using plain films to diagnose pseudogout.

What Are the Predictors of Altered Central Pain Modulation in Chronic Musculoskeletal Pain Populations? A Systematic Review.

PubMed

Clark, Jacqui; Nijs, Jo; Yeowell, Gillian; Goodwin, Peter Charles

2017-09-01

Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation. To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations. This is a systematic review in accordance with supplemented PRISMA guidelines. A systematic search was performed by 2 mutually blinded reviewers. Relevant articles were screened by title and abstract from Medline, Embase, PubMed, CINAHL, and Web of Science electronic databases. Alternative sources were also sought to locate missed potential articles. Eligibility included studies published in English, adults aged 18 to 65, musculoskeletal pain, baseline measurements taken at the pre-morbid or acute stage, > 3-month follow-up time after pain onset, and primary outcome measures specific to altered central pain modulation. Studies were excluded where there were concurrent diseases or they were non-predictive studies. Risk of bias was assessed using the quality in prognostic studies (QUIPS) tool. Study design, demographics, musculoskeletal region, inclusion/exclusion criteria, measurement timelines, predictor and primary outcome measures, and results were extracted. Data were synthesized qualitatively and strength of evidence was scored using the grading of recommendations, assessment, development, and evaluations (GRADE) scoring system. Nine eligible articles were located, in various musculoskeletal populations (whiplash, n = 2; widespread pain, n = 5; temporomandibular disorder, n = 2). Moderate evidence was found for 2 predictive factors of altered central pain modulation: 1) high sensory sensitivity (using genetic testing or quantitative sensory tests), and 2) psychological factors (somatization and poor self-expectation of recovery), at a pre-morbid or acute stage baseline. At the times of the article publications, the current definitions and clinical guidelines for identifying altered central pain modulation were not yet available. Careful interpretation of the information provided using current knowledge and published guidelines was necessary to extract information specific to altered central pain modulation in some of the studies, avoiding unwarranted assumptions. Premorbid and acute stage high sensory sensitivity and/or somatization are the strongest predictors of altered central pain modulation in chronic musculoskeletal pain to date. This is the first systematic review specifically targeting altered central pain modulation as the primary outcome in musculoskeletal pain populations. Early identification of people at risk of developing chronic pain with altered central pain modulation may guide clinicians in appropriate management, diminishing the burden of persistent pain on patients and heath care providers alike. Systematic Review Registration no.: PROSPERO 2015:CRD42015032394.Key words: Predictive factors, pre-morbid and acute stage baselines, altered central pain modulation, chronic musculoskeletal pain, sensory processing, somatization.

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

PubMed Central

Ramsden, Christopher E.; Domenichiello, Anthony F.; Yuan, Zhi-Xin; Sapio, Matthew R.; Keyes, Gregory S.; Mishra, Santosh K.; Gross, Jacklyn R.; Majchrzak-Hong, Sharon; Zamora, Daisy; Horowitz, Mark S.; Davis, John M.; Sorokin, Alexander V.; Dey, Amit; LaPaglia, Danielle M.; Wheeler, Joshua J.; Vasko, Michael R.; Mehta, Nehal N.; Mannes, Andrew J.; Iadarola, Michael J.

2018-01-01

Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy-or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene–related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber–mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch. PMID:28831021

Diagnostic accuracy of an identification tool for localized neuropathic pain based on the IASP criteria.

PubMed

Mayoral, Víctor; Pérez-Hernández, Concepción; Muro, Inmaculada; Leal, Ana; Villoria, Jesús; Esquivias, Ana

2018-04-27

Based on the clear neuroanatomical delineation of many neuropathic pain (NP) symptoms, a simple tool for performing a short structured clinical encounter based on the IASP diagnostic criteria was developed to identify NP. This study evaluated its accuracy and usefulness. A case-control study was performed in 19 pain clinics within Spain. A pain clinician used the experimental screening tool (the index test, IT) to assign the descriptions of non-neuropathic (nNP), non-localized neuropathic (nLNP), and localized neuropathic (LNP) to the patients' pain conditions. The reference standard was a formal clinical diagnosis provided by another pain clinician. The accuracy of the IT was compared with that of the Douleur Neuropathique en 4 questions (DN4) and the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS). Six-hundred and sixty-six patients were analyzed. There was a good agreement between the IT and the reference standard (kappa =0.722). The IT was accurate in distinguishing between LNP and nLNP (83.2% sensitivity, 88.2% specificity), between LNP and the other pain categories (nLNP + nNP) (80.0% sensitivity, 90.7% specificity), and between NP and nNP (95.5% sensitivity, 89.1% specificity). The accuracy in distinguishing between NP and nNP was comparable with that of the DN4 and the LANSS. The IT took a median of 10 min to complete. A novel instrument based on an operationalization of the IASP criteria can not only discern between LNP and nLNP, but also provide a high level of diagnostic certainty about the presence of NP after a short clinical encounter.

Gender expression, sexual orientation and pain sensitivity in women.

PubMed

Vigil, Jacob M; Rowell, Lauren N; Lutz, Charlotte

2014-01-01

Despite a growing body of literature investigating sex differences with regard to pain, surprisingly little research has been conducted on the influence of various aspects of self-identity, including gender expression and sexual orientation, on pain sensitivity within each sex, particularly among women. In men, dispositional femininity is linked to greater clinical pain and trait masculinity is associated with higher pain thresholds. To examine whether gender expression and sexual orientation are associated with within-sex differences in ischemic pain sensitivity in healthy young women. A convenience sample of 172 females (mean age 21.4 years; range 18 to 30 years of age; 56.0% white, 89% heterosexual) performed an ischemic pain task in counterbalanced order. Desired levels of dispositional femininity for a preferred romantic partner and self-described levels of personal dispositional femininity were measured. Compared with heterosexual women, lesbian and bisexual women reported lower pain intensity ratings early in the discomfort task. Irrespective of sexual orientation, attraction to more feminine romantic partners and dispositional masculinity were correlated with lower pain intensity, and with higher pain thresholds and tolerance levels. These preliminary findings suggest that within-sex differences in sexual orientation and other aspects of identity, irrespective of biological sex, may be important to consider when examining experimental pain performance and clinical pain experiences. Larger investigations of the psychophysiological relationships among sexual orientation, gender expression and pain sensitivity are warranted. These findings may have implications for differences in clinical pain sensitivity of lesbian and bisexual women compared with heterosexual women.

Central sensitization in chronic low back pain: A narrative review.

PubMed

Sanzarello, Ilaria; Merlini, Luciano; Rosa, Michele Attilio; Perrone, Mariada; Frugiuele, Jacopo; Borghi, Raffaele; Faldini, Cesare

2016-11-21

Low back pain is one of the four most common disorders in all regions, and the greatest contributor to disability worldwide, adding 10.7% of total years lost due to this health state. The etiology of chronic low back pain is, in most of the cases (up to 85%), unknown or nonspecific, while the specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon. Central sensitization has been recently recognized as a potential pathophysiological mechanism underlying a group of chronic pain conditions, and may be a contributory factor for a sub-group of patients with chronic low back pain. The purposes of this narrative review are twofold. First, to describe central sensitization and its symptoms and signs in patients with chronic pain disorders in order to allow its recognition in patients with nonspecific low back pain. Second, to provide general treatment principles of chronic low back pain with particular emphasis on pharmacotherapy targeting central sensitization.

Temperament as a modulating factor of pain sensitivity in combat sport athletes.

PubMed

Leźnicka, Katarzyna; Starkowska, Anna; Tomczak, Maciej; Cięszczyk, Paweł; Białecka, Monika; Ligocka, Maria; Żmijewski, Piotr; Pawlak, Maciej

2017-10-15

The aim of this study was to characterise the temperament of combat athletes in comparison to that of individuals who do not practise any sports with regard to pain sensitivity measured with the cold pressor test (CPT) and pressure pain threshold (PPT). The study involved 284 healthy men, aged 18 to 43years. The first group consisted of 198 combat athletes, including boxing (n=19), mixed martial arts (MMA) (n=97) and karate (n=82), aged from 18 to 43years. The control group consisted of 86 subjects between the ages of 18 and 26years, academic students not practising any sport professionally. Pain threshold and pain tolerance were evaluated using the CPT and a pressure algometer. Temperament was measured with the Formal Characteristics of Behaviour - Temperament Inventory (FCB-TI). The contact athletes showed much higher tolerance to pain than the control group using both tools: CPT (p=0.007) and PPT (p<0.001). In athletes, but not in controls, relationships were noted between BMI and endurance (r=0.20; p=0.004), BMI and activity (r=-0.283; p<0.001), BMI and pain threshold (r=0.15; p<0.05), and BMI and pain tolerance (r=0.30; p<0.001), when measured by the algometer - this necessitating adjustment for further analysis. The athletes and students in the study groups differed significantly with regard to intensity of four temperamental traits, but after BMI adjustments only group differences in Preservation, Sensory sensitivity and Emotional reactivity remained significant'. These differences indicate individual differences in perception and reaction to external stimuli. Significantly higher pain tolerance (CPT and PPT) in the athletes studied was related to specific psychological features. The obtained results of temperamental characteristics may indicate higher resilience of the nervous system in combat athletes in comparison to non-athletes. Copyright © 2017 Elsevier Inc. All rights reserved.

Sensory Over-Responsiveness among Healthy Subjects is Associated with a Pronociceptive State.

PubMed

Weissman-Fogel, Irit; Granovsky, Yelena; Bar-Shalita, Tami

2018-04-01

Chronic pain patients show hypersensitivity to sensory nonpainful stimuli. Sensory over-responsiveness (SOR) to innocuous daily stimuli, experienced as painful, is prevalent in 10% of the healthy population. This altered sensory processing may be an expression of overfacilitation, or a less efficient pain-inhibitory process in the pain pathways. We therefore aimed to investigate specifically the pain-inhibitory system of subjects with SOR who are otherwise healthy, not studied as of yet. Thirty healthy subjects, divided into an SOR group (n = 14) and a non-SOR group (n = 16) based on responses to the Sensory Responsiveness Questionnaire, were psychophysically tested in order to evaluate (1) hyperalgesic responses; (2) adaptation/sensitization to 14 phasic heat stimuli; (3) habituation; (4) 6-minute after-sensations; and (5) conditioned pain modulation (CPM) (ie, phasic heat stimuli applied with and without hand immersion in a hot water bath). The SOR group differed from the non-SOR group in (1) a steeper escalation in NPS ratings to temperature increase (P = 0.003), indicating hyperalgesia; (2) increased sensitization (P < 0.001); (3) habituation responses (P < 0.001); (4) enhanced pain ratings during the after-sensation (P = 0.006); and (5) no group difference was found in CPM. SOR is associated with a pronociceptive state, expressed by amplification of experimental pain, yet with sufficient inhibitory processes. Our results support previous findings of enhanced facilitation of pain-transmitting pathways but also reveal preserved inhibitory mechanisms, although they were slower to react. © 2017 World Institute of Pain.

Ultrasonographic Findings of the Shoulder in Patients with Rheumatoid Arthritis and Comparison with Physical Examination

PubMed Central

Kim, Su Ho; Seo, Young-Il

2007-01-01

The objectives of this study were: 1) to identify the ultrasonographic (US) abnormalities and 2) to compare the findings of physical examination with US findings in rheumatoid arthritis (RA) patients with shoulder pain. We studied 30 RA patients. Physical examination was performed systemically as follows: 1) area of tenderness; 2) range of passive and active shoulder motion; 3) impingement tests; 4) maneuvers for determining the location of the tendon lesions. US investigations included the biceps, the supraspinatus, infraspinatus, and subscapularis tendons; the subacromial-subdeltoid bursa; and the glenohumeral and acromioclavicular joints. Thirty RA patients with 35 painful and 25 non-painful shoulders were examined. The range of motion affected the most by shoulder pain was abduction. The most frequent US finding of shoulder joint was effusion in the long head of the biceps tendon. Among the rotator cuff tendons, subscapularis was the most frequently involved. Tendon tear was also common among non-painful shoulders. Physical examination used for the diagnosis of shoulder pain had low sensitivity and specificity for detecting abnormalities in the rheumatoid shoulder joint. In conclusion, US abnormalities showed frequent tendon tears in our RA patients. Physical examination had low sensitivity and specificity for detecting rotator cuff tear in the rheumatoid shoulder joint. PMID:17728506

Slow Temporal Summation of Pain for Assessment of Central Pain Sensitivity and Clinical Pain of Fibromyalgia Patients

PubMed Central

Staud, Roland; Weyl, Elizabeth E.; Riley, Joseph L.; Fillingim, Roger B.

2014-01-01

Background In healthy individuals slow temporal summation of pain or wind-up (WU) can be evoked by repetitive heat-pulses at frequencies of ≥.33 Hz. Previous WU studies have used various stimulus frequencies and intensities to characterize central sensitization of human subjects including fibromyalgia (FM) patients. However, many trials demonstrated considerable WU-variability including zero WU or even wind-down (WD) at stimulus intensities sufficient for activating C-nociceptors. Additionally, few WU-protocols have controlled for contributions of individual pain sensitivity to WU-magnitude, which is critical for WU-comparisons. We hypothesized that integration of 3 different WU-trains into a single WU-response function (WU-RF) would not only control for individuals’ pain sensitivity but also better characterize their central pain responding including WU and WD. Methods 33 normal controls (NC) and 38 FM patients participated in a study of heat-WU. We systematically varied stimulus intensities of.4 Hz heat-pulse trains applied to the hands. Pain summation was calculated as difference scores of 1st and 5th heat-pulse ratings. WU-difference (WU-Δ) scores related to 3 heat-pulse trains (44°C, 46°C, 48°C) were integrated into WU-response functions whose slopes were used to assess group differences in central pain sensitivity. WU-aftersensations (WU-AS) at 15 s and 30 s were used to predict clinical FM pain intensity. Results WU-Δ scores linearly accelerated with increasing stimulus intensity (p<.001) in both groups of subjects (FM>NC) from WD to WU. Slope of WU-RF, which is representative of central pain sensitivity, was significantly steeper in FM patients than NC (p<.003). WU-AS predicted clinical FM pain intensity (Pearson’s r = .4; p<.04). Conclusions Compared to single WU series, WU-RFs integrate individuals’ pain sensitivity as well as WU and WD. Slope of WU-RFs was significantly different between FM patients and NC. Therefore WU-RF may be useful for assessing central sensitization of chronic pain patients in research and clinical practice. PMID:24558475

Effects of Tetrodotoxin in Mouse Models of Visceral Pain

PubMed Central

González-Cano, Rafael; Tejada, Miguel Ángel; Artacho-Cordón, Antonia; Nieto, Francisco Rafael; Entrena, José Manuel; Wood, John N.; Cendán, Cruz Miguel

2017-01-01

Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis. The subcutaneous administration of TTX dose-dependently inhibited the number of pain-related behaviors in all evaluated pain models and reversed the referred mechanical hyperalgesia (examined by stimulation of the abdomen with von Frey filaments) induced by capsaicin and cyclophosphamide, but not that induced by mustard oil. Morphine inhibited both pain responses and the referred mechanical hyperalgesia in all tests. Conditional nociceptor‑specific Nav1.7 knockout mice treated with TTX showed the same responses as littermate controls after the administration of the algogens. No motor incoordination after the administration of TTX was observed. These results suggest that blockade of TTX-sensitive sodium channels, but not Nav1.7 subtype alone, by systemic administration of TTX might be a potential therapeutic strategy for the treatment of visceral pain. PMID:28635651

The body fades away: investigating the effects of transparency of an embodied virtual body on pain threshold and body ownership.

PubMed

Martini, Matteo; Kilteni, Konstantina; Maselli, Antonella; Sanchez-Vives, Maria V

2015-09-29

The feeling of "ownership" over an external dummy/virtual body (or body part) has been proven to have both physiological and behavioural consequences. For instance, the vision of an "embodied" dummy or virtual body can modulate pain perception. However, the impact of partial or total invisibility of the body on physiology and behaviour has been hardly explored since it presents obvious difficulties in the real world. In this study we explored how body transparency affects both body ownership and pain threshold. By means of virtual reality, we presented healthy participants with a virtual co-located body with four different levels of transparency, while participants were tested for pain threshold by increasing ramps of heat stimulation. We found that the strength of the body ownership illusion decreases when the body gets more transparent. Nevertheless, in the conditions where the body was semi-transparent, higher levels of ownership over a see-through body resulted in an increased pain sensitivity. Virtual body ownership can be used for the development of pain management interventions. However, we demonstrate that providing invisibility of the body does not increase pain threshold. Therefore, body transparency is not a good strategy to decrease pain in clinical contexts, yet this remains to be tested.

The body fades away: investigating the effects of transparency of an embodied virtual body on pain threshold and body ownership

PubMed Central

Martini, Matteo; Kilteni, Konstantina; Maselli, Antonella; Sanchez-Vives, Maria V.

2015-01-01

The feeling of “ownership” over an external dummy/virtual body (or body part) has been proven to have both physiological and behavioural consequences. For instance, the vision of an “embodied” dummy or virtual body can modulate pain perception. However, the impact of partial or total invisibility of the body on physiology and behaviour has been hardly explored since it presents obvious difficulties in the real world. In this study we explored how body transparency affects both body ownership and pain threshold. By means of virtual reality, we presented healthy participants with a virtual co-located body with four different levels of transparency, while participants were tested for pain threshold by increasing ramps of heat stimulation. We found that the strength of the body ownership illusion decreases when the body gets more transparent. Nevertheless, in the conditions where the body was semi-transparent, higher levels of ownership over a see-through body resulted in an increased pain sensitivity. Virtual body ownership can be used for the development of pain management interventions. However, we demonstrate that providing invisibility of the body does not increase pain threshold. Therefore, body transparency is not a good strategy to decrease pain in clinical contexts, yet this remains to be tested. PMID:26415748

Effect of a single session of muscle-biased therapy on pain sensitivity: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Gay, Charles W; Alappattu, Meryl J; Coronado, Rogelio A; Horn, Maggie E; Bishop, Mark D

2013-01-01

Background Muscle-biased therapies (MBT) are commonly used to treat pain, yet several reviews suggest evidence for the clinical effectiveness of these therapies is lacking. Inadequate treatment parameters have been suggested to account for inconsistent effects across studies. Pain sensitivity may serve as an intermediate physiologic endpoint helping to establish optimal MBT treatment parameters. The purpose of this review was to summarize the current literature investigating the short-term effect of a single dose of MBT on pain sensitivity in both healthy and clinical populations, with particular attention to specific MBT parameters of intensity and duration. Methods A systematic search for articles meeting our prespecified criteria was conducted using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, in accordance with guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analysis. Relevant characteristics from studies included type, intensity, and duration of MBT and whether short-term changes in pain sensitivity and clinical pain were noted with MBT application. Study results were pooled using a random-effects model to estimate the overall effect size of a single dose of MBT on pain sensitivity as well as the effect of MBT, dependent on comparison group and population type. Results Reports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups, where 10 groups received active agents, 11 received sham/inert treatments, and eight received no treatment. MBT demonstrated a favorable and consistent ability to modulate pain sensitivity. Short-term modulation of pain sensitivity was associated with short-term beneficial effects on clinical pain. Intensity of MBT, but not duration, was linked with change in pain sensitivity. A meta-analysis was conducted on 17 studies that assessed the effect of MBT on pressure pain thresholds. The results suggest that MBT had a favorable effect on pressure pain thresholds when compared with no-treatment and sham/inert groups, and effects comparable with those of other active treatments. Conclusion The evidence supports the use of pain sensitivity measures by future research to help elucidate optimal therapeutic parameters for MBT as an intermediate physiologic marker. PMID:23403507

An experimental study of pain upon stimulation of the nasal and sinus cavities.

PubMed

Clerico, Dean M

2014-01-01

To map different areas of pain sensitivity and to determine the existence and/or pattern of referred pain from upon stimulating the sinonasal cavity. Experimental human study. Mechanical and electrical stimulations to various anatomical structures and areas of the nasal and sinus cavities were conducted on nine volunteers. Intensity, location and character of pain were recorded in all subjects. The postero-superior (cephalic) aspect of the nasal cavity, primarily the anterior face of the sphenoid sinus and the superior turbinate, were the most sensitive sites, and the antero-inferior (caudal) region was the least sensitive. Referred pain to the head and face was reported by several subjects. Topographical differences in pain sensitivity exist in the sinonasal cavity. The phenomenon of referred pain from the nasal cavity was demonstrated. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuro Emotional Technique for the treatment of trigger point sensitivity in chronic neck pain sufferers: A controlled clinical trial

PubMed Central

Bablis, Peter; Pollard, Henry; Bonello, Rod

2008-01-01

Background Trigger points have been shown to be active in many myofascial pain syndromes. Treatment of trigger point pain and dysfunction may be explained through the mechanisms of central and peripheral paradigms. This study aimed to investigate whether the mind/body treatment of Neuro Emotional Technique (NET) could significantly relieve pain sensitivity of trigger points presenting in a cohort of chronic neck pain sufferers. Methods Sixty participants presenting to a private chiropractic clinic with chronic cervical pain as their primary complaint were sequentially allocated into treatment and control groups. Participants in the treatment group received a short course of Neuro Emotional Technique that consists of muscle testing, general semantics and Traditional Chinese Medicine. The control group received a sham NET protocol. Outcome measurements included pain assessment utilizing a visual analog scale and a pressure gauge algometer. Pain sensitivity was measured at four trigger point locations: suboccipital region (S); levator scapulae region (LS); sternocleidomastoid region (SCM) and temporomandibular region (TMJ). For each outcome measurement and each trigger point, we calculated the change in measurement between pre- and post- treatment. We then examined the relationships between these measurement changes and six independent variables (i.e. treatment group and the above five additional participant variables) using forward stepwise General Linear Model. Results The visual analog scale (0 to 10) had an improvement of 7.6 at S, 7.2 at LS, 7.5 at SCM and 7.1 at the TMJ in the treatment group compared with no improvement of at S, and an improvement of 0.04 at LS, 0.1 at SCM and 0.1 at the TMJ point in the control group, (P < 0.001). Conclusion After a short course of NET treatment, measurements of visual analog scale and pressure algometer recordings of four trigger point locations in a cohort of chronic neck pain sufferers were significantly improved when compared to a control group which received a sham protocol of NET. Chronic neck pain sufferers may benefit from NET treatment in the relief of trigger point sensitivity. Further research including long-term randomised controlled trials for the effect of NET on chronic neck pain, and other chronic pain syndromes are recommended. Trial Registration This trial has been registered and allocated the Australian Clinical Trials Registry (ACTR) number ACTRN012607000358448. The ACTR has met the requirements of the ICMJE's trials registration policy and is an ICMJE acceptable registry. PMID:18495042

Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.

PubMed

Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef

2014-09-01

Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (P<0.001). Tramadol increased the PWT by 336% in CCI rats (P<0.001) and by 16% in sham (P<0.05). On the EPM, CCI rats spent 45% less time than sham on the open arms of the maze (P<0.05). Tramadol increased the time spent on the open arms of CCI rats by 67% (P<0.05) and had no significant effect on sham. During the FST, CCI rats showed 28% longer immobility than sham (P<0.01). Tramadol reduced the immobility time in CCI rats by 22% (P<0.001), while having no effect on sham. Tramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP. Copyright © 2014 Elsevier Inc. All rights reserved.

Pain intensity, temperament traits and social support as determinants of trauma symptoms in patients suffering from rheumatoid arthritis and low-back pain.

PubMed

Rzeszutek, Marcin; Oniszczenko, Włodzimierz; Schier, Katarzyna; Biernat-Kałuża, Edyta; Gasik, Robert

2016-04-01

The main goal of our study was to investigate the relationship between age, duration of pain, pain intensity, temperament traits as postulated by the Regulative Theory of Temperament (RTT), social support dimensions and the level of trauma symptoms, as appear in post-traumatic stress disorder (PTSD) in a sample of 300 patients suffering from chronic pain in two groups comprised of 150 patients with a clinical diagnosis of rheumatoid arthritis (RA) and 150 patients with a clinical diagnosis of low-back pain (LBP). They were analyzed together as a one group of 300 patients with chronic pain. Temperament was measured with the Formal Characteristics of Behaviour - Temperament Inventory (FCB-TI). Social support was tested with the Berlin Social Support Scales (BSSS). The Numerical Rating Scale (NRS-11) was used to measure pain intensity. The level of trauma symptoms was assessed with the Post-Traumatic Stress Disorder Factorial Version Inventory (PTSDF). The results of our study suggest that the intensity of pain, participants' age, Emotional Reactivity and Sensory Sensitivity as temperament traits, need for support, and actually received social support were related to the level of trauma symptoms. The sum of the squared semi-partial correlations showed that all six variables (age, pain intensity, Emotional Reactivity, Sensory Sensitivity, need for support and actually received support), account for 20% of the variance of general trauma symptoms level. The importance of temperament traits, social support and trauma symptoms should be taken into an account in psychotherapy accompanying pharmacotherapy for pain. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

PubMed Central

Brandow, Amanda M.; Wandersee, Nancy J.; Dasgupta, Mahua; Hoffmann, Raymond G.; Hillery, Cheryl A.; Stucky, Cheryl L.; Panepinto, Julie A.

2016-01-01

Summary Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: 1) SCD baseline and controls and 2) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean±standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32.4±11.6 vs. 22.9±7.6, P=0.0009). SP in SCD pain was higher than baseline (78.1±43.4 vs. 32.4±11.6, P=0.004). Haemolysis correlated with increased SP: Hb (r=−0.7, P=0.0002), reticulocyte count (r=0.61, P=0.0016), bilirubin (r=0.68, P=0.0216), LDH (r=0.62, P=0.0332), aspartate aminotransferase (r=0.68, P=0.003). Patients taking hydroxycarbamide had increased SP (β=29.2, P=0.007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment. PMID:27539682

Gender expression, sexual orientation and pain sensitivity in women

PubMed Central

Vigil, Jacob M; Rowell, Lauren N; Lutz, Charlotte

2014-01-01

BACKGROUND: Despite a growing body of literature investigating sex differences with regard to pain, surprisingly little research has been conducted on the influence of various aspects of self-identity, including gender expression and sexual orientation, on pain sensitivity within each sex, particularly among women. In men, dispositional femininity is linked to greater clinical pain and trait masculinity is associated with higher pain thresholds. OBJECTIVES: To examine whether gender expression and sexual orientation are associated with within-sex differences in ischemic pain sensitivity in healthy young women. METHODS: A convenience sample of 172 females (mean age 21.4 years; range 18 to 30 years of age; 56.0% white, 89% heterosexual) performed an ischemic pain task in counterbalanced order. Desired levels of dispositional femininity for a preferred romantic partner and self-described levels of personal dispositional femininity were measured. RESULTS: Compared with heterosexual women, lesbian and bisexual women reported lower pain intensity ratings early in the discomfort task. Irrespective of sexual orientation, attraction to more feminine romantic partners and dispositional masculinity were correlated with lower pain intensity, and with higher pain thresholds and tolerance levels. DISCUSSION: These preliminary findings suggest that within-sex differences in sexual orientation and other aspects of identity, irrespective of biological sex, may be important to consider when examining experimental pain performance and clinical pain experiences. CONCLUSION: Larger investigations of the psychophysiological relationships among sexual orientation, gender expression and pain sensitivity are warranted. These findings may have implications for differences in clinical pain sensitivity of lesbian and bisexual women compared with heterosexual women. PMID:24575419

Predictors and Moderators of Post-traumatic Stress Disorder: An Investigation of Anxiety Sensitivity and Resilience in Individuals with Chronic Pain.

PubMed

Lies, July; Lau, Shi Ting; Jones, Lester E; Jensen, Mark P; Tan, Gabriel

2017-03-01

Anxiety sensitivity has been proposed as a psychological vulnerability factor for post-traumatic stress disorder (PTSD). Studies have also supported the protective role of resilience for overcoming the negative effects of trauma exposure. Given the linkages between anxiety sensitivity, resilience, trauma exposure and post-traumatic stress, this study explored the potential moderating roles of anxiety sensitivity and resilience on the association between trauma history and PTSD symptoms in a sample of individuals with chronic pain. A total of 100 patients with chronic pain were recruited from a large public hospital. Patients who had pain lasting for more than 3 months and a pain intensity rating of at least 4/10 were included. The study participants were administered measures of PTSD symptoms (PTSD Checklist - Civilian Version), resilience (Brief Resilient Coping Scale) and anxiety sensitivity (Anxiety Sensitivity Index). An analysis of outcome measures indicated that anxiety sensitivity and resilience were independently associated with PTSD symptoms, where βs were 0.57 and -0.23, respectively. The relationship between trauma and PTSD symptom severity was also moderated by anxiety sensitivity. Trauma history was associated with higher PTSD symptom severity only in those with high anxiety sensitivity. However, contrary to the hypotheses, resilience did not serve as a moderator. There are potential benefits of PTSD interventions that increase resilience and decrease anxiety sensitivity in individuals with chronic pain, especially for those who have experienced a traumatic event. Given that the presence of PTSD symptomatology in chronic pain populations negatively impact patient well-being, it would be important for clinicians to assess, monitor and treat PTSD in individuals with chronic pain.

Recurrent rotator cuff tear: is ultrasound imaging reliable?

PubMed

Gilat, Ron; Atoun, Ehud; Cohen, Ornit; Tsvieli, Oren; Rath, Ehud; Lakstein, Dror; Levy, Ofer

2018-02-02

The diagnostic workup of the painful shoulder after rotator cuff repair (RCR) can be quite challenging. The aim of this study was to assess the reliability of ultrasonography (US) for the detection of recurrent rotator cuff tears in patients with shoulder pain after RCR. We hypothesized that US for the diagnosis of recurrent rotator cuff tear after RCR would not prove to be reliable when compared with surgical arthroscopic confirmation (gold standard). In this cohort study (diagnosis), we retrospectively analyzed the data of 39 patients with shoulder pain after arthroscopic RCR who had subsequently undergone US, followed by revision arthroscopy. The rotator cuff was evaluated first using US for the presence of retears. Thereafter, revision arthroscopy was performed, and the diagnosis was either established or disproved. The sensitivity and specificity of US were assessed in reference to revision arthroscopy (gold standard). A rotator cuff retear was indicated by US in 21 patients (54%) and by revision arthroscopy in 26 patients (67%). US showed a sensitivity of 80.8% and specificity of 100% in the diagnosis of rotator cuff retears. Omission of partial rotator cuff retears resulted in a spike in sensitivity to 94.7%, with 100% specificity remaining. US imaging is a highly sensitive and specific test for the detection of recurrent rotator cuff tears, as confirmed by revision arthroscopy, in patients with a painful shoulder after primary RCR. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Sex differences in how social networks and relationship quality influence experimental pain sensitivity.

PubMed

Vigil, Jacob M; Rowell, Lauren N; Chouteau, Simone; Chavez, Alexandre; Jaramillo, Elisa; Neal, Michael; Waid, David

2013-01-01

This is the first study to examine how both structural and functional components of individuals' social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one's significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual's social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed.

Sex Differences in How Social Networks and Relationship Quality Influence Experimental Pain Sensitivity

PubMed Central

Vigil, Jacob M.; Rowell, Lauren N.; Chouteau, Simone; Chavez, Alexandre; Jaramillo, Elisa; Neal, Michael; Waid, David

2013-01-01

This is the first study to examine how both structural and functional components of individuals’ social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one’s significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual’s social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed. PMID:24223836

Clinical effects of buprenorphine on open field behaviour and gait symmetry in healthy and lame weaned piglets.

PubMed

Meijer, Ellen; van Nes, Arie; Back, Willem; van der Staay, Franz Josef

2015-12-01

Lameness in pigs decreases animal welfare and economic profit for the farmer. An important reason for impaired welfare in lame animals is pain due to lameness. No direct measurement of pain is possible in animals, and methods to indirectly detect and quantify the amount of pain an animal is experiencing are urgently needed. In this study, two methods to assess pain associated with lameness in pigs were evaluated to determine if they were sensitive enough to detect a lameness reduction as an effect of an experimental analgesic medication. Asymmetry associated with lameness was objectively quantified using pressure mat kinetic parameters: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Locomotor activity was assessed in an open field test. A dose of 0.04 mg/kg buprenorphine, a strong analgesic, was used to treat 10 lame pigs, while eight other lame pigs, treated with physiological saline solution, served as controls. Buprenorphine decreased lameness-associated asymmetry for pressure mat LR (P = 0.002), VI (P = 0.003) and PVP (P = 0.001) and increased activity of the lame pigs in the open field (P = 0.023), while saline-treated animals did not show any changes in asymmetry and became less active in the open field (P <0.001). It was concluded that measurement of gait asymmetry by pressure mat analysis and locomotor activity in an open field test are both sensitive enough to detect the analgesic effects of buprenorphine when used to treat moderate to severe clinical pain in a relatively small group of affected pigs. The methods used in this study may also provide promising additional tools for future research into early pain recognition and lameness treatment in pigs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cohort Removal Induces Changes in Body Temperature, Pain Sensitivity, and Anxiety-Like Behavior

PubMed Central

Takao, Keizo; Shoji, Hirotaka; Hattori, Satoko; Miyakawa, Tsuyoshi

2016-01-01

Mouse behavior is analyzed to elucidate the effects of various experimental manipulations, including gene mutation and drug administration. When the effect of a factor of interest is assessed, other factors, such as age, sex, temperature, apparatus, and housing, are controlled in experiments by matching, counterbalancing, and/or randomizing. One such factor that has not attracted much attention is the effect of sequential removal of animals from a common cage (cohort removal). Here we evaluated the effects of cohort removal on rectal temperature, pain sensitivity, and anxiety-like behavior by analyzing the combined data of a large number of C57BL/6J mice that we collected using a comprehensive behavioral test battery. Rectal temperature increased in a stepwise manner according to the position of sequential removal from the cage, consistent with previous reports. In the hot plate test, the mice that were removed first from the cage had a significantly longer latency to show the first paw response than the mice removed later. In the elevated plus maze, the mice removed first spent significantly less time on the open arms compared to the mice removed later. The results of the present study demonstrated that cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior in mice. Cohort removal also increased the plasma corticosterone concentration in mice. Thus, the ordinal position in the sequence of removal from the cage should be carefully counterbalanced between groups when the effect of experimental manipulations, including gene manipulation and drug administration, are examined using behavioral tests. PMID:27375443

Identification of clusters of individuals relevant to temporomandibular disorders and other chronic pain conditions: the OPPERA study

PubMed Central

Bair, Eric; Gaynor, Sheila; Slade, Gary D.; Ohrbach, Richard; Fillingim, Roger B.; Greenspan, Joel D.; Dubner, Ronald; Smith, Shad B.; Diatchenko, Luda; Maixner, William

2016-01-01

The classification of most chronic pain disorders gives emphasis to anatomical location of the pain to distinguish one disorder from the other (eg, back pain vs temporomandibular disorder [TMD]) or to define subtypes (eg, TMD myalgia vs arthralgia). However, anatomical criteria overlook etiology, potentially hampering treatment decisions. This study identified clusters of individuals using a comprehensive array of biopsychosocial measures. Data were collected from a case–control study of 1031 chronic TMD cases and 3247 TMD-free controls. Three subgroups were identified using supervised cluster analysis (referred to as the adaptive, pain-sensitive, and global symptoms clusters). Compared with the adaptive cluster, participants in the pain-sensitive cluster showed heightened sensitivity to experimental pain, and participants in the global symptoms cluster showed both greater pain sensitivity and greater psychological distress. Cluster membership was strongly associated with chronic TMD: 91.5% of TMD cases belonged to the pain-sensitive and global symptoms clusters, whereas 41.2% of controls belonged to the adaptive cluster. Temporomandibular disorder cases in the pain-sensitive and global symptoms clusters also showed greater pain intensity, jaw functional limitation, and more comorbid pain conditions. Similar results were obtained when the same methodology was applied to a smaller case–control study consisting of 199 chronic TMD cases and 201 TMD-free controls. During a median 3-year follow-up period of TMD-free individuals, participants in the global symptoms cluster had greater risk of developing first-onset TMD (hazard ratio = 2.8) compared with participants in the other 2 clusters. Cross-cohort predictive modeling was used to demonstrate the reliability of the clusters. PMID:26928952

Examining the Sensitivity and Specificity of 2 Screening Instruments: Odontogenic or Temporomandibular Disorder Pain?

PubMed

Fonseca Alonso, Barbara; Nixdorf, Donald R; Shueb, Sarah S; John, Mike T; Law, Alan S; Durham, Justin

2017-01-01

Two groups of patients with orofacial pains that are clinically important to distinguish from each other are patients with odontogenic pain and temporomandibular disorder (TMD) pain. The aim of this study was to determine the sensitivity and specificity of 2 screening instruments in distinguishing between patients with these types of pain. A convenience sample of patients seeking care at an endodontic clinic and an orofacial pain clinic were recruited. The 14-item dental pain questionnaire (DePaQ) was used to screen for odontogenic pain and the 6-item TMD screener was used to screen for TMD pain. Sensitivity and specificity calculations with 95% confidence intervals (CIs) were performed for both instruments, and thresholds/acceptability/performance was assessed using published guidelines. Thirty-four patients with odontogenic pain and 37 patients with TMD pain were included in this study. The sensitivity of the DePaQ was 0.85 (95% CI, 0.69-0.95), and specificity was 0.11 (95% CI, 0.03-0.25). The sensitivity of the TMD screener was 0.92 (95% CI, 0.78-0.98), and specificity was 0.59 (95% CI, 0.41-0.75). The point estimates, a single value used to estimate the population parameter, for both the DePaQ and TMD screener were "acceptable" in identifying patients who had the pain condition in question (ie, sensitivity), whereas the point estimate for appropriately identifying patients who did not have the pain condition when they did not have it (ie, specificity) was "nonacceptable" for both. The DePaQ and the TMD screener lack diagnostic accuracy for differentiating TMD from odontogenic tooth pain without adjunctive (clinical) investigation(s) or examination. However, the TMD screener has high sensitivity for identifying true positives (ie, TMD pain) and would therefore be useful as a screening instrument when one can definitively exclude odontogenic etiology for pain on clinical and radiographic grounds, for instance in endodontic practices. In this study, the negative predictive value was also high in the TMD screener, and, therefore, we can trust a negative result (ie, when the TMD screener is negative, we can be fairly certain the pain diagnosis is not TMD and rule out TMD). Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Assessment of deep dynamic mechanical sensitivity in individuals with tension-type headache: The dynamic pressure algometry.

PubMed

Palacios-Ceña, M; Wang, K; Castaldo, M; Guerrero-Peral, Á; Caminero, A B; Fernández-de-Las-Peñas, C; Arendt-Nielsen, L

2017-09-01

To explore the validity of dynamic pressure algometry for evaluating deep dynamic mechanical sensitivity by assessing its association with headache features and widespread pressure sensitivity in tension-type headache (TTH). One hundred and eighty-eight subjects with TTH (70% women) participated. Deep dynamic sensitivity was assessed with a dynamic pressure algometry set (Aalborg University, Denmark © ) consisting of 11 different rollers including fixed levels from 500 g to 5300 g. Each roller was moved at a speed of 0.5 cm/s over a 60-mm horizontal line covering the temporalis muscle. Dynamic pain threshold (DPT-level of the first painful roller) was determined and pain intensity during DPT was rated on a numerical pain rate scale (NPRS, 0-10). Headache clinical features were collected on a headache diary. As gold standard, static pressure pain thresholds (PPT) were assessed over temporalis, C5/C6 joint, second metacarpal, and tibialis anterior muscle. Side-to-side consistency between DPT (r = 0.843, p < 0.001) and pain evoked (r = 0.712; p < 0.001) by dynamic algometer was observed. DPT was moderately associated with widespread PPTs (0.526 > r > 0.656, all p < 0.001). Furthermore, pain during DPT was negatively associated with widespread PPTs (-0.370 < r < -0.162, all p < 0.05). Dynamic pressure algometry was a valid tool for assessing deep dynamic mechanical sensitivity in TTH. DPT was associated with widespread pressure sensitivity independently of the frequency of headaches supporting that deep dynamic pressure sensitivity within the trigeminal area is consistent with widespread pressure sensitivity. Assessing deep static and dynamic somatic tissue pain sensitivity may provide new opportunities for differentiated diagnostics and possibly a new tool for assessing treatment effects. The current study found that dynamic pressure algometry in the temporalis muscle was associated with widespread pressure pain sensitivity in individuals with tension-type headache. The association was independent of the frequency of headaches. Assessing deep static and dynamic somatic tissue pain sensitivity may provide new opportunities for differentiated diagnostics and possibly a tool for assessing treatment effects. © 2017 European Pain Federation - EFIC®.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Myofascial trigger points: spontaneous electrical activity and its consequences for pain induction and propagation

PubMed Central

2011-01-01

Active myofascial trigger points are one of the major peripheral pain generators for regional and generalized musculoskeletal pain conditions. Myofascial trigger points are also the targets for acupuncture and/or dry needling therapies. Recent evidence in the understanding of the pathophysiology of myofascial trigger points supports The Integrated Hypothesis for the trigger point formation; however unanswered questions remain. Current evidence shows that spontaneous electrical activity at myofascial trigger point originates from the extrafusal motor endplate. The spontaneous electrical activity represents focal muscle fiber contraction and/or muscle cramp potentials depending on trigger point sensitivity. Local pain and tenderness at myofascial trigger points are largely due to nociceptor sensitization with a lesser contribution from non-nociceptor sensitization. Nociceptor and non-nociceptor sensitization at myofascial trigger points may be part of the process of muscle ischemia associated with sustained focal muscle contraction and/or muscle cramps. Referred pain is dependent on the sensitivity of myofascial trigger points. Active myofascial trigger points may play an important role in the transition from localized pain to generalized pain conditions via the enhanced central sensitization, decreased descending inhibition and dysfunctional motor control strategy. PMID:21439050

A pilot study of myofascial release therapy compared to Swedish massage in Fibromyalgia

PubMed Central

Liptan, Ginevra; Mist, Scott; Wright, Cheryl; Arzt, Anna; Jones, Kim Dupree

2017-01-01

Summary Fibromyalgia (FM) is characterized by widespread muscle pain and soft tissue tenderness. However, a lack of definitive muscle pathology has made FM both a diagnostic and a treatment puzzle. Much of the evidence for pathology in FM lies in the central nervous system – in particular abnormal amplification of pain signals in the spinal cord – a manifestation of central sensitization. An emerging body of evidence posits that peripheral pain generated from the muscles and fascia may trigger and maintain central sensitization in FM. Since FM patients so frequently seek manual therapy to relieve muscle symptoms, the present study compared two different manual therapy techniques in a parallel study of women with FM. Eight subjects received myofascial release (MFR) while four subjects received Swedish massage, 90 min weekly for four weeks. Overall symptom burden and physical function were assessed by the Fibromyalgia Impact Questionnaire Revised (FIQ-R). A unique challenge for the manual therapist in treating conditions involving central sensitization is to determine if localized pain reduction can be achieved with targeted therapy in the context of ongoing widespread pain. Localized pain improvement was measured by a novel questionnaire developed for this study, the modified Nordic Musculoskeletal Questionnaire (NMQ). Between-group differences in FIQ-R did not reach statistical significance, but the total change scores on FIQ-R for the MFR group (mean = 10.14, SD = 16.2) trended in the hypothesized and positive direction compared to the Swedish massage group (mean = 0.33, SD = 4.93) yielding a positive Aikin separation test. Although overall modified NMQ scores improved in both groups there were no consistent focal areas of improvement for the Swedish massage group. In contrast, the MFR group reported consistent pain reductions in the neck and upper back regions on the NMQ. These data support the need for larger randomized controlled trials of MFR versus other massage techniques and support the assessment of localized pain reduction in future manual therapy studies in FM. PMID:23768283

Urine and oral fluid drug testing in support of pain management.

PubMed

Kwong, Tai C; Magnani, Barbarajean; Moore, Christine

2017-09-01

In recent years, the abuse of opioid drugs has resulted in greater prevalence of addiction, overdose, and deaths attributable to opioid abuse. The epidemic of opioid abuse has prompted professional and government agencies to issue practice guidelines for prescribing opioids to manage chronic pain. An important tool available to providers is the drug test for use in the initial assessment of patients for possible opioid therapy, subsequent monitoring of compliance, and documentation of suspected aberrant drug behaviors. This review discusses the issues that most affect the clinical utility of drug testing in chronic pain management with opioid therapy. It focuses on the two most commonly used specimen matrices in drug testing: urine and oral fluid. The advantages and disadvantages of urine and oral fluid in the entire testing process, from specimen collection and analytical methodologies to result interpretation are reviewed. The analytical sensitivity and specificity limitations of immunoassays used for testing are examined in detail to draw attention to how these shortcomings can affect result interpretation and influence clinical decision-making in pain management. The need for specific identification and quantitative measurement of the drugs and metabolites present to investigate suspected aberrant drug behavior or unexpected positive results is analyzed. Also presented are recent developments in optimization of test menus and testing strategies, such as the modification of the standard screen and reflexed-confirmation testing model by eliminating some of the initial immunoassay-based tests and proceeding directly to definitive testing by mass spectrometry assays.

Fish oil concentrate delays sensitivity to thermal nociception in mice

PubMed Central

Veigas, Jyothi M.; Williams, Paul J.; Halade, Ganesh; Rahman, Mizanur M.; Yoneda, Toshiyuki; Fernandes, Gabriel

2011-01-01

Fish oil has been used to alleviate pain associated with inflammatory conditions such as rheumatoid arthritis. The anti-inflammatory property of fish oil is attributed to the n-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid. Contrarily, vegetable oils such as safflower oil are rich in n-6 fatty acids which are considered to be mediators of inflammation. This study investigates the effect of n-3 and n-6 fatty acids rich oils as dietary supplements on the thermally induced pain sensitivity in healthy mice. C57Bl/6J mice were fed diet containing regular fish oil, concentrated fish oil formulation (CFO) and safflower oil (SO) for 6 months. Pain sensitivity was measured by plantar test and was correlated to the expression of acid sensing ion channels (ASICs), transient receptor potential vanilloid 1 (TRPV1) and c-fos in dorsal root ganglion cells. Significant delay in sensitivity to thermal nociception was observed in mice fed CFO compared to mice fed SO (p<0.05). A significant diminution in expression of ion channels such as ASIC1a (64%), ASIC13 (37%) and TRPV1 (56%) coupled with reduced expression of c-fos, a marker of neuronal activation, was observed in the dorsal root ganglion cells of mice fed CFO compared to that fed SO. In conclusion, we describe here the potential of fish oil supplement in reducing sensitivity to thermal nociception in normal mice. PMID:21345372

Spinal Manipulative Therapy Specific Changes In Pain Sensitivity In Individuals With Low Back Pain (NCT01168999)

PubMed Central

Bialosky, Joel E; George, Steven Z; Horn, Maggie E; Price, Donald D; Staud, Roland; Robinson, Michael E

2013-01-01

Spinal Manipulative Therapy (SMT) is effective for some individuals experiencing low back pain (LBP); however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with LBP to receive SMT, placebo SMT, placebo SMT with the instructional set, “The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people”, or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over two weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following two weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (p= 0.05, partial η2= 0.07). Group dependent differences were not observed for changes in pain intensity and disability at two week. Participant satisfaction was greatest following the enhanced placebo SMT. PMID:24361109

Pain increases during sympathetic arousal in patients with complex regional pain syndrome.

PubMed

Drummond, P D; Finch, P M; Skipworth, S; Blockey, P

2001-10-09

To investigate the effect of sympathetic arousal on pain and vasomotor responses in healthy control subjects and patients with complex regional pain syndrome (CRPS), and to determine whether pain increases in patients with particular symptoms. In experiments 1 and 2, capsaicin was applied to the forearm of 24 healthy subjects to induce thermal hyperalgesia. Vascular responses were monitored and subjects rated thermal hyperalgesia before and after being startled (experiment 1), and before, during, and after mental arithmetic, breath holding, forehead cooling, the Valsalva maneuver, and a cold pressor test in experiment 2. In a third experiment, sensitivity to heat, cold, and mechanical stimulation was investigated in 61 patients with CRPS. Pain ratings and vascular and electrodermal responses were recorded after patients were startled and during forehead cooling. In experiment 1, thermal hyperalgesia decreased in healthy control subjects after they were startled, and digital blood vessels constricted symmetrically. In experiment 2, thermal hyperalgesia decreased during and after other forms of sympathetic arousal. However, in experiment 3, ratings of clinical pain increased during forehead cooling or after being startled in over 70% of patients with CRPS. Pain increased most consistently during forehead cooling in patients with cold allodynia or punctate allodynia. Digital blood vessels constricted more intensely on the symptomatic than the nonsymptomatic side in patients with CRPS during sympathetic arousal. Normal inhibitory influences on pain during sympathetic arousal are compromised in the majority of patients with CRPS. The augmented vasoconstrictor response in the symptomatic limb during sympathetic arousal is consistent with adrenergic supersensitivity. An adrenergic sensitivity in nociceptive afferents might contribute to pain and hyperalgesia during sympathetic arousal in certain patients with CRPS.

Involvement of α2-adrenoceptors in inhibitory and facilitatory pain modulation processes.

PubMed

Vo, L; Drummond, P D

2016-03-01

In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only produces hyperalgesia at the site of stimulation but also reduces sensitivity to pressure-pain on the ipsilateral side of the forehead. In addition, HFS augments the ipsilateral trigeminal nociceptive blink reflex and intensifies the ipsilateral component of conditioned pain modulation. The aim of this study was to determine whether α2-adrenoceptors mediate these ipsilateral nociceptive influences. The α2-adrenoceptor antagonist yohimbine was administered to 22 participants in a double-blind, placebo-controlled crossover study. In each session, thermal and mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, the combined effect of HFS and yohimbine on the nociceptive blink reflex and on conditioned pain modulation was explored. In this paradigm, the conditioning stimulus was cold pain in the ipsilateral or contralateral temple, and the test stimulus was electrically evoked pain in the forearm. Blood pressure and electrodermal activity increased for several hours after yohimbine administration, consistent with blockade of central α2-adrenoceptors. Yohimbine not only augmented the nociceptive blink reflex ipsilateral to HFS but also intensified the inhibitory influence of ipsilateral temple cooling on electrically evoked pain at the HFS-treated site in the forearm. Yohimbine had no consistent effect on primary or secondary hyperalgesia in the forearm or on pressure-pain in the ipsilateral forehead. These findings imply involvement of α2-adrenoceptors both in ipsilateral antinociceptive and pronociceptive pain modulation processes. However, a mechanism not involving α2-adrenoceptors appears to mediate analgesia in the ipsilateral forehead after HFS. © 2015 European Pain Federation - EFIC®

What we know about primary dysmenorrhea today: a critical review.

PubMed

Iacovides, Stella; Avidon, Ingrid; Baker, Fiona C

2015-01-01

Primary dysmenorrhea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynecological condition that affects between 45 and 95% of menstruating women. Despite the high prevalence, dysmenorrhea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. This review reports on current knowledge, particularly with regards to the impact and consequences of recurrent menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhea. Comprehensive literature searches on primary dysmenorrhea were performed using the electronic databases PubMed, Google Scholar and the Cochrane Library. Full-text manuscripts published between the years 1944 and 2015 were reviewed for relevancy and reference lists were cross-checked for additional relevant studies. In combination with the word 'dysmenorrhea' one or more of the following search terms were used to obtain articles published in peer-reviewed journals only: pain, risk factors, etiology, experimental pain, clinical pain, adenomyosis, chronic pain, women, menstrual cycle, hyperalgesia, pain threshold, pain tolerance, pain sensitivity, pain reactivity, pain perception, central sensitization, quality of life, sleep, treatment, non-steroidal anti-inflammatory drugs. Women with dysmenorrhea, compared with women without dysmenorrhea, have greater sensitivity to experimental pain both within and outside areas of referred menstrual pain. Importantly, the enhanced pain sensitivity is evident even in phases of the menstrual cycle when women are not experiencing menstrual pain, illustrating that long-term differences in pain perception extend outside of the painful menstruation phase. This enhanced pain sensitivity may increase susceptibility to other chronic pain conditions in later life; dysmenorrhea is a risk factor for fibromyalgia. Further, dysmenorrheic pain has an immediate negative impact on quality of life, for up to a few days every month. Women with primary dysmenorrhea have a significantly reduced quality of life, poorer mood and poorer sleep quality during menstruation compared with their pain-free follicular phase, and compared with the menstruation phase of pain-free control women. The prescribed first-line therapy for menstrual pain remains non-steroidal anti-inflammatory drugs, which are effective in relieving daytime and night-time pain. Further study is needed to determine whether effectively blocking dysmenorrheic pain ameliorates risk for the development of chronic pain disorders and to explore whether it is possible to prevent the development-and not just treat-severe dysmenorrheic pain in adolescent girls. In conclusion, we demonstrate the extensive multi-factorial impact of dysmenorrhea and we encourage and direct researchers to necessary future studies. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

THERMAL SENSITIVITY ACROSS AGES AND DURING CHRONIC FENTANYL ADMINISTRATION IN RATS

PubMed Central

Mitzelfelt, Jeremiah D.; Carter, Christy S.; Morgan, Drake

2013-01-01

Rationale Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear. Objectives Thus the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, 24 months). Methods Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28 days of fentanyl administration (1.0 mg/kg/day), and 28 days of withdrawal. Results Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals. Conclusions Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies. PMID:23900640

Analgesic effects of stem bark extracts of Trichilia monadelpha (Thonn.) JJ De Wilde.

PubMed

Woode, Eric; Amoh-Barimah, Ama Kyeraa; Abotsi, Wonder Kofi Mensah; Ainooson, George Kwaw; Owusu, George

2012-01-01

Various parts of Trichilia monadelpha (Thonn) JJ De Wilde (Fam. Meliaceae) are used in Ghanaian traditional medicine for the treatment of painful and inflammatory conditions. The present study examined the analgesic properties of the petroleum ether (PEE), ethyl acetate (EAE), and the hydro-ethanolic (HAE) extract of the stem bark of the plant in murine models. PEE, EAE, and HAE were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models. The possible mechanisms of the antinociceptive action were also examined with various antagonists in the formalin test. HAE, EAE, and PEE, each at doses of 10-100 mg/kg orally, and the positive controls (morphine and diclofenac) elicited significant dose-dependent antinociceptive activity in the chemical (acetic acid abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models in rodents. The antinociceptive effect of HAE was partly or wholly reversed by systemic administration of atropine, naloxone, and glibenclamide. The antinociceptive effects of EAE and PEE were inhibited by atropine. The extracts HAE, EAE, and PEE caused dose-related antinociception in chemical, thermal, and mechanical models of pain in animals. The mechanism of action of HAE involves an interaction with muscarinic cholinergic, adenosinergic, opioidergic pathways, and ATP-sensitive K+ channels while that of EAE and PEE involve the muscarinic cholinergic system.

Linguistic adaptation, validation and comparison of 3 routinely used neuropathic pain questionnaires.

PubMed

Li, Jun; Feng, Yi; Han, Jisheng; Fan, Bifa; Wu, Dasheng; Zhang, Daying; Du, Dongping; Li, Hui; Lim, Jian; Wang, Jiashuang; Jin, Yi; Fu, Zhijian

2012-01-01

Neuropathic pain questionnaires are efficient diagnostic tools for neuropathic pain and play an important role in neuropathic pain epidemiologic studies in China. No comparison data was available in regards to the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), the Neuropathic Pain Questionnaire (NPQ) and ID Pain within and among the same population. To achieve a linguistic adaptation, validation, and comparison of Chinese versions of the 3 neuropathic pain questionnaires (LANSS, NPQ and ID Pain). A nonrandomized, controlled, prospective, multicenter trial. Ten pain centers in China. Two forward translations followed by comparison and reconciliation of the translations. Comparison of the 2 backward translations with the original version was made to establish consistency and accuracy of the translations. Pilot testing and pain specialists' evaluations were also required. A total of 140 patients were enrolled in 10 centers throughout China: 70 neuropathic pain patients and 70 nociceptive pain patients. Reliability (Cronbach's alpha coefficients and Guttman split-half coefficients) and validity (sensitivity, specificity, positive and negative predictive values, receiver operating characteristic [ROC] curves and the area under the ROC curves) of the 3 questionnaires were determined. ROC curves and the area under the ROC curves of the 3 questionnaires were also compared. Chinese versions of LANSS, NPQ and ID Pain had a good reliability (Cronbach's alpha coefficients and Guttman split-half coefficients were greater than 0.7). Sensitivity, specificity, positive and negative predictive values of the Chinese versions of LANSS and ID Pain were considerably high ( > 80%). The area under the ROC curves of LANSS and ID Pain was significantly higher than that of NPQ (P < 0.05). There was no statistically significant difference between the area under the ROC curves of LANSS and ID Pain (P > 0.05). The study was based on patients with a high school degree or above, which limited the application of the 3 neuropathic pain questionnaires to patients with lower educational levels. The Chinese versions of LANSS and ID Pain developed and validated by this study can be used as a diagnostic tool in differentiating neuropathic pain in patients whose native language is Chinese (Mandarin).

Pediatric Chest Pain-Low-Probability Referral: A Multi-Institutional Analysis From Standardized Clinical Assessment and Management Plans (SCAMPs®), the Pediatric Health Information Systems Database, and the National Ambulatory Medical Care Survey.

PubMed

Harahsheh, Ashraf S; O'Byrne, Michael L; Pastor, Bill; Graham, Dionne A; Fulton, David R

2017-11-01

We conducted a study to assess test characteristics of red-flag criteria for identifying cardiac disease causing chest pain and technical charges of low-probability referrals. Accuracy of red-flag criteria was ascertained through study of chest pain Standardized Clinical Assessment and Management Plans (SCAMPs®) data. Patients were divided into 2 groups: Group1 (concerning clinical elements) and Group2 (without). We compared incidence of cardiac disease causing chest pain between these 2 groups. Technical charges of Group 2 were analyzed using the Pediatric Health Information System database. Potential savings for the US population was estimated using National Ambulatory Medical Care Survey data. Fifty-two percent of subjects formed Group 1. Cardiac disease causing chest pain was identified in 8/1656 (0.48%). No heart disease was identified in patients in Group 2 ( P = .03). Applying red-flags in determining need for referral identified patients with cardiac disease causing chest pain with 100% sensitivity. Median technical charges for Group 2, over a 4-year period, were US2014$775 559. Eliminating cardiac testing of low-probability referrals would save US2014$3 775 182 in technical charges annually. Red-flag criteria were an effective screen for children with chest pain. Eliminating cardiac testing in children without red-flags for referral has significant technical charge savings.

High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation.

PubMed

Vo, L; Drummond, P D

2013-03-01

In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.

Ethnicity Interacts with the OPRM1 Gene in Experimental Pain Sensitivity

PubMed Central

Hastie, Barbara A.; Riley, Joseph L.; Kaplan, Lee; Herrera, Dyanne G.; Campbell, Claudia M.; Virtusio, Kathrina; Mogil, Jeffrey S.; Wallace, Margaret R.; Fillingim, Roger B.

2013-01-01

Robust inter-individual variation in pain sensitivity has been observed and recent evidence suggests that some of the variability may be genetically-mediated. Our previous data revealed significantly higher pressure pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared to those with two consensus alleles. Moreover, ethnic differences in pain sensitivity have been widely reported. Yet, little is known about the potential interactive associations of ethnicity and genotype with pain perception. This study aimed to identify ethnic differences in OPRM1 allelic associations with experimental pain responses. Two-hundred and forty-seven healthy young adults from three ethnic groups (81 African Americans; 79 non-white Hispanics; and 87 non-Hispanic whites) underwent multiple experimental pain modalities (thermal, pressure, ischemic, cold pressor). Few African Americans (7.4%) expressed the rare allele of OPRM1 compared to non-Hispanic-whites and Hispanics (28.7% vs. 27.8%, respectively). Across the entire sample, OPRM1 genotype did not significantly affect pain sensitivity. However, analysis in each ethnic group separately revealed significant genotype effects for most pain modalities among non-Hispanic-whites (ps<0.05) but not Hispanics or African Americans. The G allele was associated with decreased pain sensitivity among whites only; a trend in the opposite direction emerged in Hispanics. The reasons for this dichotomy are unclear but may involve ethnic differences in haplotypic structure or A118G may be a tag-SNP linked to other functional polymorphisms. These findings demonstrate an ethnic-dependent association of OPRM1 genotype with pain sensitivity. Additional research is warranted to uncover the mechanisms influencing these relationships. PMID:22717102

Pain Processing after Social Exclusion and Its Relation to Rejection Sensitivity in Borderline Personality Disorder

PubMed Central

Bungert, Melanie; Koppe, Georgia; Niedtfeld, Inga; Vollstädt-Klein, Sabine; Schmahl, Christian

2015-01-01

Objective There is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that “social pain,” as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity. Method Twenty unmedicated female BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game (cyberball), with the conditions for exclusion, inclusion, and a control condition with predefined game rules. Each cyberball block was followed by a temperature stimulus (with a subjective pain intensity of 60% in half the cases). The cerebral responses were measured by functional magnetic resonance imaging. The Adult Rejection Sensitivity Questionnaire was used to assess rejection sensitivity. Results Higher temperature heat stimuli had to be applied to BPD patients relative to HCs to reach a comparable subjective experience of painfulness in both groups, which suggested a general hyposensitivity to pain in BPD patients. Social exclusion led to a subjectively reported hypersensitivity to physical pain in both groups that was accompanied by an enhanced activation in the anterior insula and the thalamus. In BPD, physical pain processing after exclusion was additionally linked to enhanced posterior insula activation. After inclusion, BPD patients showed reduced amygdala activation during pain in comparison with HC. In BPD patients, higher rejection sensitivity was associated with lower activation differences during pain processing following social exclusion and inclusion in the insula and in the amygdala. Discussion Despite the similar behavioral effects in both groups, BPD patients differed from HC in their neural processing of physical pain depending on the preceding social situation. Rejection sensitivity further modulated the impact of social exclusion on neural pain processing in BPD, but not in healthy controls. PMID:26241850

Night-shift work is associated with increased pain perception.

PubMed

Matre, Dagfinn; Knardahl, Stein; Nilsen, Kristian Bernhard

2017-05-01

Objectives The aim of the present study was to determine whether shift workers exhibit increased perception of experimentally induced pain after working night shifts. Methods The study was a paired cross-over design with two sleep conditions, after at least two nights of habitual sleep and after two consecutive night shifts at work. Fifty-three nurses in rotating shift work participated. The sensitivity to electrically induced pain, heat pain, cold pain, pressure pain and pain inhibition was determined experimentally in each sleep condition. Sleepiness and vigilance were also assessed. Results Night-shift work (NSW) increased the sensitivity to electrically induced pain and heat pain (P≤0.001). Relative to habitual sleep, electrically induced pain increased by 22.3% and heat pain increased by 26.5%. The sensitivity to cold and pressure pain did not change, changes relative to habitual sleep was <5% (P>0.5). Pain inhibition was 66.9% stronger after NSW versus after habitual sleep (P<0.001). Sleepiness (measured with the Karolinska Sleepiness Scale) increased from 4.1 after habitual sleep to 6.9 after NSW (P<0.001). Vigilance decreased after NSW, measured as a 0.03-second decrease in reaction time (P<0.005). Conclusions Changes in pain sensitivity after NSW is measurable with clinically relevant effect sizes and may be an important marker for studies comparing the physiological effects of different shift work schedules. Explanations for the differential effect on different pain modalities should be a focus for future studies.

Quick Discrimination of Adelta and C Fiber Mediated Pain Based on Three Verbal Descriptors

PubMed Central

Beissner, Florian; Brandau, Amadeus; Henke, Christian; Felden, Lisa; Baumgärtner, Ulf; Treede, Rolf-Detlef; Oertel, Bruno G.; Lötsch, Jörn

2010-01-01

Background Aδ and C fibers are the major pain-conducting nerve fibers, activate only partly the same brain areas, and are differently involved in pain syndromes. Whether a stimulus excites predominantly Aδ or C fibers is a commonly asked question in basic pain research but a quick test was lacking so far. Methodology/Principal Findings Of 77 verbal descriptors of pain sensations, “pricking”, “dull” and “pressing” distinguished best (95% cases correctly) between Aδ fiber mediated (punctate pressure produced by means of von Frey hairs) and C fiber mediated (blunt pressure) pain, applied to healthy volunteers in experiment 1. The sensation was assigned to Aδ fibers when “pricking” but neither “dull” nor “pressing” were chosen, and to C fibers when the sum of the selections of “dull” or “pressing” was greater than that of the selection of “pricking”. In experiment 2, with an independent cohort, the three-descriptor questionnaire achieved sensitivity and specificity above 0.95 for distinguishing fiber preferential non-mechanical induced pain (laser heat, exciting Aδ fibers, and 5-Hz electric stimulation, exciting C fibers). Conclusion A three-item verbal rating test using the words “pricking”, “dull”, and “pressing” may provide sufficient information to characterize a pain sensation evoked by a physical stimulus as transmitted via Aδ or via C fibers. It meets the criteria of a screening test by being easy to administer, taking little time, being comfortable in handling, and inexpensive while providing high specificity for relevant information. PMID:20886070

Cultural Adaptation and Psychometric Evaluation of the Spanish Version of the Nursing Outcome "Pain Control" in Primary Care Patients with Chronic Pain.

PubMed

Bellido-Vallejo, José Carlos; Pancorbo-Hidalgo, Pedro Luis

2017-10-01

The control of chronic pain is a major challenge for patients and health care professionals. To culturally adapt the Nursing Outcomes Classification outcome "Pain control" (PC) to the Spanish health care setting and to analyze its psychometric properties and sensitivity to change. A study of three stages was designed: (1) Translation and cultural adaptation by translation-back-translation method, (2) content validation by a group of experts, and (3) observational-longitudinal study in patients with chronic pain. Patient sampling was nonprobabilistic, and participants completed forms and questionnaires and responded to a question on pain. Statistical analysis included descriptive analysis, content validity index (for global PC and each indicator), principal component analysis, Spearman's test, Cronbach's α, Cohen's κ coefficient, and Wilcoxon range test. The new Spanish version of "Pain control" was semantically equivalent to the original, with a mean content validity index of 0.96. The clinical study included 88 patients with long-term pain, and the mean (standard deviation) interval between assessments (baseline and final) was 29.33 (8.05) days. Thirteen indicators were organized into two components. There was divergent but not convergent validity with the Change Pain Scale and Brief Pain Inventory. Between-observer agreement was κ = 0.48 and internal consistency was α = 0.85. No differences were found between mean baseline and final scores. The Spanish version of "Pain control," culturally adapted and structured in two components (13 indicators), is useful to assess and monitor pain control in patients with chronic pain. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Alfentanil and placebo analgesia: no sex differences detected in models of experimental pain.

PubMed

Olofsen, Erik; Romberg, Raymonda; Bijl, Hans; Mooren, René; Engbers, Frank; Kest, Benjamin; Dahan, Albert

2005-07-01

To assess whether patient sex contributes to the interindividual variability in alfentanil analgesic sensitivity, the authors compared male and female subjects for pain sensitivity after alfentanil using a pharmacokinetic-pharmacodynamic modeling approach. Healthy volunteers received a 30-min alfentanil or placebo infusion on two occasions. Analgesia was measured during the subsequent 6 h by assaying tolerance to transcutaneous electrical stimulation (eight men and eight women) of increasing intensity or using visual analog scale scores during treatment with noxious thermal heat (five men and five women). Sedation was concomitantly measured. Population pharmacokinetic-pharmacodynamic models were applied to the analgesia and sedation data using NONMEM. For electrical pain, the placebo and alfentanil models were combined post hoc. Alfentanil and placebo analgesic responses did not differ between sexes. The placebo effect was successfully incorporated into the alfentanil pharmacokinetic-pharmacodynamic model and was responsible for 20% of the potency of alfentanil. However, the placebo effect did not contribute to the analgesic response variability. The pharmacokinetic-pharmacodynamic analysis of the electrical and heat pain data yielded similar values for the potency parameter, but the blood-effect site equilibration half-life was significantly longer for electrical pain (7-9 min) than for heat pain (0.2 min) or sedation (2 min). In contrast to the ample literature demonstrating sex differences in morphine analgesia, neither sex nor subject expectation (i.e., placebo) contributes to the large between-subject response variability with alfentanil analgesia. The difference in alfentanil analgesia onset and offset between pain tests is discussed.

Pain-Suppressed Behaviors in the Red-tailed Hawk 1 (Buteo jamaicensis)

PubMed Central

Mazor-Thomas, Jana E.; Mann, Phyllis E.; Karas, Alicia Z.; Tseng, Flo

2014-01-01

Our ability to provide analgesia in wild and exotic patients is hampered by a lack of species-specific information on effective drugs and protocols. One contributing factor is the difficulty of applying data from traditional laboratory tests of nociception to clinical conditions frequently involving combinations of inflammatory, mechanical, and neuropathic pain. Pain-suppressed behaviors have become a valuable predictor of clinical utility in other species; in this study we extend this framework to red -tailed hawks in a wildlife hospital, in an attempt to develop a new, humane testing method for birds of prey. We scored six behaviors in hawks hospitalized either for orthopedic trauma or for non-painful conditions. These behaviors included: movement about the cage, grooming, head motions, foot shifts, beak clacks, and rouse. Movement, head motions, and beak clacks were all significantly reduced in hawks with recent orthopedic injury, but not in hawks with healed or minor injuries (P<0.05 for all behaviors). However, it should be noted that due to stringent admission criteria, and the difficulties inherent in studying naturally-occuring injury in wild patients, this study only included -subjects in four experimental groups, and this limited our ability to fully investigate confounds within our data. A follow-up experiment was conducted to determine potential effects of buprenorphine, a mu opioid agonist, on the behaviors listed above. Buprenorphine in the absence of pain caused minor, non-significant decreases in most behaviors, and had no effect on head movement frequency. This suggests that head movements in particular may be sensitive to pain but not to sedative side-effects of buprenorphine. Overall, red -tailed hawks with recent orthopedic trauma show consistent and marked red uctions in several normal maintenance behaviors. Head movements, reported for the first time in this study as a potential marker of pain in birds, in particular seem to be insensitive to sedative side effects of buprenorphine, while being a sensitive measu re of affective state in hawks with painful injuries. These behaviors can be scored humanely and with minimal expense, and should be considered for further research on pain and analgesia in avian species. PMID:24904190

Evaluation of Analgesia, Tolerance, and the Mechanism of Action of Morphine-6-O-Sulfate Across Multiple Pain Modalities in Sprague-Dawley Rats.

PubMed

Yadlapalli, Jai Shankar K; Dogra, Navdeep; Walbaum, Anqi W; Wessinger, William D; Prather, Paul L; Crooks, Peter A; Dobretsov, Maxim

2017-09-01

Morphine-6-O-sulfate (M6S) is a mixed μ/δ-opioid receptor (OR) agonist and potential alternative to morphine for treatment of chronic multimodal pain. To provide more support for this hypothesis, the antinociceptive effects of M6S and morphine were compared in tests that access a range of pain modalities, including hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold tests. Acutely, M6S was 2- to 3-fold more potent than morphine in HPT and PST tests, specifically, derived from best-fit analysis of dose-response relationships of morphine/M6S half-effective dose (ED50) ratios (lower, upper 95% confidence interval [CI]) were 2.8 (2.0-5.8) in HPT and 2.2 (2.1, 2.4) in PST tests. No differences in analgesic drug potencies were detected in the PPT test (morphine/M6S ED50 ratio 1.2 (95% CI, 0.8-1.4). After 7 to 9 days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all 3 pain tests. Morphine-tolerant rats were not crosstolerant to M6S. The antinociceptive effects of M6S were not sensitive to κ-OR antagonists. However, the δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 55% ± 4% (95% CI, 39-75) in the HPT test, 94% ± 4% (95% CI, 84-105) in the PST test, and 5% ± 17% (95% CI, -47 to 59) or 51% ± 14% (95% CI, 14-84; 6 rats per each group) in the paw pressure threshold test when examined acutely or after 7 days of chronic treatment, respectively. Activity via δ-ORs thus appears to be an important determinant of M6S action. M6S also exhibited favorable antinociceptive and tolerance profiles compared with morphine in 3 different antinociceptive assays, indicating that M6S may serve as a useful alternative for rotation in morphine-tolerant subjects.

Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats

PubMed Central

2013-01-01

Background A scale validated in one language is not automatically valid in another language or culture. The purpose of this study was to validate the English version of the UNESP-Botucatu multidimensional composite pain scale (MCPS) to assess postoperative pain in cats. The English version was developed using translation, back-translation, and review by individuals with expertise in feline pain management. In sequence, validity and reliability tests were performed. Results Of the three domains identified by factor analysis, the internal consistency was excellent for ‘pain expression’ and ‘psychomotor change’ (0.86 and 0.87) but not for ‘physiological variables’ (0.28). Relevant changes in pain scores at clinically distinct time points (e.g., post-surgery, post-analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and moderate to very good agreement between blinded observers and ‘gold standard’ evaluations, supported criterion validity. The cut-off point for rescue analgesia was > 7 (range 0–30 points) with 96.5% sensitivity and 99.5% specificity. Conclusions The English version of the UNESP-Botucatu-MCPS is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The cut-off point for rescue analgesia provides an additional tool for guiding analgesic therapy. PMID:23867090

Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats.

PubMed

Brondani, Juliana T; Mama, Khursheed R; Luna, Stelio P L; Wright, Bonnie D; Niyom, Sirirat; Ambrosio, Jennifer; Vogel, Pamela R; Padovani, Carlos R

2013-07-17

A scale validated in one language is not automatically valid in another language or culture. The purpose of this study was to validate the English version of the UNESP-Botucatu multidimensional composite pain scale (MCPS) to assess postoperative pain in cats. The English version was developed using translation, back-translation, and review by individuals with expertise in feline pain management. In sequence, validity and reliability tests were performed. Of the three domains identified by factor analysis, the internal consistency was excellent for 'pain expression' and 'psychomotor change' (0.86 and 0.87) but not for 'physiological variables' (0.28). Relevant changes in pain scores at clinically distinct time points (e.g., post-surgery, post-analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and moderate to very good agreement between blinded observers and 'gold standard' evaluations, supported criterion validity. The cut-off point for rescue analgesia was > 7 (range 0-30 points) with 96.5% sensitivity and 99.5% specificity. The English version of the UNESP-Botucatu-MCPS is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The cut-off point for rescue analgesia provides an additional tool for guiding analgesic therapy.

Gender role expectations of pain: relationship to experimental pain perception

PubMed Central

Wise, Emily A.; Price, Donald D.; Myers, Cynthia D.; Heft, Marc W.; Robinson, Michael E.

2008-01-01

The primary purpose of this study was to investigate the influence of an individual’s Gender Role Expectations of Pain (GREP) on experimental pain report. One hundred and forty-eight subjects (87 females and 61 males) subjects underwent thermal testing and were asked to report pain threshold, pain tolerance, VAS ratings of pain intensity and unpleasantness, and a computerized visual analogue scales (VAS) rating of pain intensity during the procedure. Subjects completed the GREP questionnaire to assess sex-related stereotypic attributions of pain sensitivity, pain endurance, and willingness to report pain. Consistent with previous research, significant sex differences emerged for measures of pain threshold, pain tolerance, and pain unpleasantness. After statistically controlling for age, GREP scores were significant predictors of threshold, tolerance, and pain unpleasantness, accounting for an additional 7, 11, and 21% of the variance, respectively. Sex remained a significant predictor of pain tolerance in hierarchical regression analyses after controlling for GREP scores. Results provide support for two competing but not mutually exclusive hypotheses related to the sex differences in experimental pain. Both psychosocial factors and first-order, biological sex differences remain as viable explanations for differences in experimental pain report between the sexes. It appears that GREP do play a part in determining an individual’s pain report and may be contributing to the sex differences in the laboratory setting. PMID:11973007

Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial.

PubMed

Malfliet, Anneleen; Kregel, Jeroen; Coppieters, Iris; De Pauw, Robby; Meeus, Mira; Roussel, Nathalie; Cagnie, Barbara; Danneels, Lieven; Nijs, Jo

2018-04-16

Effective treatments for chronic spinal pain are essential to reduce the related high personal and socioeconomic costs. To compare pain neuroscience education combined with cognition-targeted motor control training with current best-evidence physiotherapy for reducing pain and improving functionality, gray matter morphologic features, and pain cognitions in individuals with chronic spinal pain. Multicenter randomized clinical trial conducted from January 1, 2014, to January 30, 2017, among 120 patients with chronic nonspecific spinal pain in 2 outpatient hospitals with follow-up at 3, 6, and 12 months. Participants were randomized into an experimental group (combined pain neuroscience education and cognition-targeted motor control training) and a control group (combining education on back and neck pain and general exercise therapy). Primary outcomes were pain (pressure pain thresholds, numeric rating scale, and central sensitization inventory) and function (pain disability index and mental health and physical health). There were 22 men and 38 women in the experimental group (mean [SD] age, 39.9 [12.0] years) and 25 men and 35 women in the control group (mean [SD] age, 40.5 [12.9] years). Participants in the experimental group experienced reduced pain (small to medium effect sizes): higher pressure pain thresholds at primary test site at 3 months (estimated marginal [EM] mean, 0.971; 95% CI, -0.028 to 1.970) and reduced central sensitization inventory scores at 6 months (EM mean, -5.684; 95% CI, -10.589 to -0.780) and 12 months (EM mean, -6.053; 95% CI, -10.781 to -1.324). They also experienced improved function (small to medium effect sizes): significant and clinically relevant reduction of disability at 3 months (EM mean, -5.113; 95% CI, -9.994 to -0.232), 6 months (EM mean, -6.351; 95% CI, -11.153 to -1.550), and 12 months (EM mean, -5.779; 95% CI, -10.340 to -1.217); better mental health at 6 months (EM mean, 36.496; 95% CI, 7.998-64.995); and better physical health at 3 months (EM mean, 39.263; 95% CI, 9.644-66.882), 6 months (EM mean, 53.007; 95% CI, 23.805-82.209), and 12 months (EM mean, 32.208; 95% CI, 2.402-62.014). Pain neuroscience education combined with cognition-targeted motor control training appears to be more effective than current best-evidence physiotherapy for improving pain, symptoms of central sensitization, disability, mental and physical functioning, and pain cognitions in individuals with chronic spinal pain. Significant clinical improvements without detectable changes in brain gray matter morphologic features calls into question the relevance of brain gray matter alterations in this population. clinicaltrials.gov Identifier: NCT02098005.

Assessment of nerve involvement in the lumbar spine: agreement between magnetic resonance imaging, physical examination and pain drawing findings.

PubMed

Bertilson, Bo C; Brosjö, Eva; Billing, Hans; Strender, Lars-Erik

2010-09-10

Detection of nerve involvement originating in the spine is a primary concern in the assessment of spine symptoms. Magnetic resonance imaging (MRI) has become the diagnostic method of choice for this detection. However, the agreement between MRI and other diagnostic methods for detecting nerve involvement has not been fully evaluated. The aim of this diagnostic study was to evaluate the agreement between nerve involvement visible in MRI and findings of nerve involvement detected in a structured physical examination and a simplified pain drawing. Sixty-one consecutive patients referred for MRI of the lumbar spine were - without knowledge of MRI findings - assessed for nerve involvement with a simplified pain drawing and a structured physical examination. Agreement between findings was calculated as overall agreement, the p value for McNemar's exact test, specificity, sensitivity, and positive and negative predictive values. MRI-visible nerve involvement was significantly less common than, and showed weak agreement with, physical examination and pain drawing findings of nerve involvement in corresponding body segments. In spine segment L4-5, where most findings of nerve involvement were detected, the mean sensitivity of MRI-visible nerve involvement to a positive neurological test in the physical examination ranged from 16-37%. The mean specificity of MRI-visible nerve involvement in the same segment ranged from 61-77%. Positive and negative predictive values of MRI-visible nerve involvement in segment L4-5 ranged from 22-78% and 28-56% respectively. In patients with long-standing nerve root symptoms referred for lumbar MRI, MRI-visible nerve involvement significantly underestimates the presence of nerve involvement detected by a physical examination and a pain drawing. A structured physical examination and a simplified pain drawing may reveal that many patients with "MRI-invisible" lumbar symptoms need treatment aimed at nerve involvement. Factors other than present MRI-visible nerve involvement may be responsible for findings of nerve involvement in the physical examination and the pain drawing.

Efficacy of knee joint aspiration in patients with acute ACL injury in the emergency department.

PubMed

Wang, Joon Ho; Lee, Jin Hyuck; Cho, Youngsuk; Shin, Jung Min; Lee, Byung Hoon

2016-08-01

To evaluate the influence of joint aspiration on the sensitivity of physical examination for diagnosing acute anterior cruciate ligament (ACL) lesion in the second outpatient-department (OPD) follow-up referred from emergency department (ED). This retrospective study included sixty patients underwent ACL reconstruction with initial visit at ED. They were divided into two groups based on the presence or absence of joint aspiration at ED. All participants were referred to second OPD follow-up within 7-14days after the injury. Clinical manifestation (including visual analogue scale (VAS) for pain, range of motion (ROM), and severity of knee effusion) and physical examination (Lachman test and pivot shift test) were checked in ED and the second OPD follow-up. The group of patients with joint aspiration (G1) showed substantial decreases in mean values of VAS for pain (p=0.005), ROM (p=0.001), and effusion level (p<0.001), even higher VAS and effusion level and lower ROM at the initial visit of ED than the other group (G2). The sensitivity of positive Lachman and pivot shift test was significantly (p<0.05) increased following knee joint aspiration. Positive Lachman test was recorded at 76.5% in the second follow-up in G1, which was significantly (p=0.047) higher than that (47.6%) in G2. The percentage of positive pivot shift test was recorded at 76.5% in the second follow-up in G1, which as significantly (p<0.001) higher than that (31.0%) in G2. Knee joint aspiration in acute ACL injury with suspected hemarthrosis could be considered as a diagnostic procedure. Joint aspiration in early medical attendance might be able to lower pain scores or raise the sensitivity of physical examination for diagnosing acute ACL injury at follow up visit in orthopedic outpatient department. Retrospective cohort study III. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel approach to spinal 3-D kinematic assessment using inertial sensors: Towards effective quantitative evaluation of low back pain in clinical settings.

PubMed

Ashouri, Sajad; Abedi, Mohsen; Abdollahi, Masoud; Dehghan Manshadi, Farideh; Parnianpour, Mohamad; Khalaf, Kinda

2017-10-01

This paper presents a novel approach for evaluating LBP in various settings. The proposed system uses cost-effective inertial sensors, in conjunction with pattern recognition techniques, for identifying sensitive classifiers towards discriminate identification of LB patients. 24 healthy individuals and 28 low back pain patients performed trunk motion tasks in five different directions for validation. Four combinations of these motions were selected based on literature, and the corresponding kinematic data was collected. Upon filtering (4th order, low pass Butterworth filter) and normalizing the data, Principal Component Analysis was used for feature extraction, while Support Vector Machine classifier was applied for data classification. The results reveal that non-linear Kernel classification can be adequately employed for low back pain identification. Our preliminary results demonstrate that using a single inertial sensor placed on the thorax, in conjunction with a relatively simple test protocol, can identify low back pain with an accuracy of 96%, a sensitivity of %100, and specificity of 92%. While our approach shows promising results, further validation in a larger population is required towards using the methodology as a practical quantitative assessment tool for the detection of low back pain in clinical/rehabilitation settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study.

PubMed

Monfort, Jordi; Pujol, Jesús; Contreras-Rodríguez, Oren; Llorente-Onaindia, Jone; López-Solà, Marina; Blanco-Hinojo, Laura; Vergés, Josep; Herrero, Marta; Sánchez, Laura; Ortiz, Hector; Montañés, Francisco; Deus, Joan; Benito, Pere

2017-06-21

Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI. Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain. fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test. fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration. The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Autoerythrocyte sensitization syndrome presenting with general neurodermatitis

PubMed Central

Oh, In Young; Ko, Eun Jung

2013-01-01

Autoerythrocyte sensitization syndrome (AES) was first described by Gardner and Diamond in 1955, when four women with painful bruising were depicted. Patients with AES typically present with the development of recurrent, spontaneous, painful ecchymosis, frequently preceded by a prodrome of pain or itching of the skin. The patients are sensitive to their own red blood cells injected intradermally, and underlying coagulopathies are thought to be absent. We introduce a 70-year-old woman presenting with recurrent episodes of painful bruising on the trunk and extremities. PMID:23956968

Pain perception in people with Down syndrome: a synthesis of clinical and experimental research

PubMed Central

McGuire, Brian E.; Defrin, Ruth

2015-01-01

People with an intellectual disability experience both acute and chronic pain with at least the same frequency as the general population. However, considerably less is known about the pain perception of people with Down syndrome. In this review paper, we evaluated the available clinical and experimental evidence. Some experimental studies of acute pain have indicated that pain threshold was higher than normal but only when using a reaction time method to measure pain sensitivity. However, when reaction time is not part of the calculation of the pain threshold, pain sensitivity in people with Down syndrome is in fact lower than normal (more sensitive to pain). Clinical studies of chronic pain have shown that people with an intellectual disability experience chronic pain and within that population, people with Down syndrome also experience chronic pain, but the precise prevalence of chronic pain in Down syndrome has yet to be established. Taken together, the literature suggests that people with Down syndrome experience pain, both acute and chronic, with at least the same frequency as the rest of the population. Furthermore, the evidence suggests that although acute pain expression appears to be delayed, once pain is registered, there appears to be a magnified pain response. We conclude by proposing an agenda for future research in this area. PMID:26283936

Standardizing procedures to study sensitization of human spinal nociceptive processes: comparing parameters for temporal summation of the nociceptive flexion reflex (TS-NFR).

PubMed

Terry, Ellen L; France, Christopher R; Bartley, Emily J; Delventura, Jennifer L; Kerr, Kara L; Vincent, Ashley L; Rhudy, Jamie L

2011-09-01

Temporal summation of pain (TS-pain) is the progressive increase in pain ratings during a series of noxious stimulations. TS-pain has been used to make inferences about sensitization of spinal nociceptive processes; however, pain report can be biased thereby leading to problems with this inference. Temporal summation of the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception) can potentially overcome report bias, but there have been few attempts (generally with small Ns) to standardize TS-NFR procedures. In this study, 50 healthy participants received 25 series of noxious electric stimulations to evoke TS-NFR and TS-pain. Goals were to: 1) determine the stimulation frequency that best elicits TS-NFR and reduces electromyogram (EMG) contamination from muscle tension, 2) determine the minimum number of stimulations per series before NFR summation asymptotes, 3) compare NFR definition intervals (90-150ms vs. 70-150ms post-stimulation), and 4) compare TS-pain and TS-NFR when different stimulation frequencies are used. Results indicated TS-NFR should be elicited by a series of three stimuli delivered at 2.0Hz and TS-NFR should be defined from a 70-150ms post-stimulation scoring interval. Unfortunately, EMG contamination from muscle tension was greatest during 2.0Hz series. Discrepancies were noted between TS-NFR and TS-pain which raise concerns about using pain ratings to infer changes in spinal nociceptive processes. And finally, some individuals did not have reliable NFRs when the stimulation intensity was set at NFR threshold during TS-NFR testing; therefore, a higher intensity is needed. Implications of findings are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Validity and reliability of the Spanish version of the DN4 (Douleur Neuropathique 4 questions) questionnaire for differential diagnosis of pain syndromes associated to a neuropathic or somatic component

PubMed Central

Perez, Concepcion; Galvez, Rafael; Huelbes, Silvia; Insausti, Joaquin; Bouhassira, Didier; Diaz, Silvia; Rejas, Javier

2007-01-01

Background This study assesses the validity and reliability of the Spanish version of DN4 questionnaire as a tool for differential diagnosis of pain syndromes associated to a neuropathic (NP) or somatic component (non-neuropathic pain, NNP). Methods A study was conducted consisting of two phases: cultural adaptation into the Spanish language by means of conceptual equivalence, including forward and backward translations in duplicate and cognitive debriefing, and testing of psychometric properties in patients with NP (peripheral, central and mixed) and NNP. The analysis of psychometric properties included reliability (internal consistency, inter-rater agreement and test-retest reliability) and validity (ROC curve analysis, agreement with the reference diagnosis and determination of sensitivity, specificity, and positive and negative predictive values in different subsamples according to type of NP). Results A sample of 164 subjects (99 women, 60.4%; age: 60.4 ± 16.0 years), 94 (57.3%) with NP (36 with peripheral, 32 with central, and 26 with mixed pain) and 70 with NNP was enrolled. The questionnaire was reliable [Cronbach's alpha coefficient: 0.71, inter-rater agreement coefficient: 0.80 (0.71–0.89), and test-retest intra-class correlation coefficient: 0.95 (0.92–0.97)] and valid for a cut-off value ≥ 4 points, which was the best value to discriminate between NP and NNP subjects. Discussion This study, representing the first validation of the DN4 questionnaire into another language different than the original, not only supported its high discriminatory value for identification of neuropathic pain, but also provided supplemental psychometric validation (i.e. test-retest reliability, influence of educational level and pain intensity) and showed its validity in mixed pain syndromes. PMID:18053212

Nociceptor Sensitization Depends on Age and Pain Chronicity123

PubMed Central

Dodge, Amanda K.

2016-01-01

Abstract Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite the greater burden of chronic pain on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months old) and aged (>18 months old) mice exhibited prominent pain behaviors during both acute (2 day) and chronic (8 week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (AM) fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following two important findings: (1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury; and (2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive. PMID:26866058

The HEART score with high-sensitive troponin T at presentation: ruling out patients with chest pain in the emergency room.

PubMed

Santi, Luca; Farina, Gabriele; Gramenzi, Annagiulia; Trevisani, Franco; Baccini, Margherita; Bernardi, Mauro; Cavazza, Mario

2017-04-01

The HEART score is a simple scoring system, ranging from 0 to 10, specifically developed for risk stratification of patients with undifferentiated chest pain. It has been validated for the conventional troponin, but not for high-sensitive troponin. We assess a modified version of the HEART score using a single high-sensitivity troponin T dosage at presentation, regardless of symptom duration, and with different ECG criteria to evaluate if the patients with a low HEART score could be safely discharged early. The secondary aim was to confirm a statistically significant difference in each HEART score group (low 0-3, intermediate 4-6, high 7-10) in the occurrence of major adverse cardiac events at 30 and 180 days. We retrospectively analyzed the HEART score of 1597 consecutive patients admitted to the Emergency Department of our Hospital for chest pain between January 1 and June 30, 2014. Of these, 190 did not meet the inclusion criteria and 29 were lost to follow-up. None of the 512 (37.2 %) patients with a low HEART score had an event within 180 days. The difference between the cumulative incidences of events in the three HEART score groups was statistically significant (P < 0.0001). We demonstrate that it might be possible to safely discharge Emergency Department chest pain patients with a low modified HEART score after an initial determination of high-sensitive troponin T, without a prolonged observation period or an additional cardiac testing.

A cross-sectional study of pain sensitivity, disease-activity assessment, mental health, and fibromyalgia status in rheumatoid arthritis.

PubMed

Joharatnam, Nalinie; McWilliams, Daniel F; Wilson, Deborah; Wheeler, Maggie; Pande, Ira; Walsh, David A

2015-01-20

Pain remains the most important problem for people with rheumatoid arthritis (RA). Active inflammatory disease contributes to pain, but pain due to non-inflammatory mechanisms can confound the assessment of disease activity. We hypothesize that augmented pain processing, fibromyalgic features, poorer mental health, and patient-reported 28-joint disease activity score (DAS28) components are associated in RA. In total, 50 people with stable, long-standing RA recruited from a rheumatology outpatient clinic were assessed for pain-pressure thresholds (PPTs) at three separate sites (knee, tibia, and sternum), DAS28, fibromyalgia, and mental health status. Multivariable analysis was performed to assess the association between PPT and DAS28 components, DAS28-P (the proportion of DAS28 derived from the patient-reported components of visual analogue score and tender joint count), or fibromyalgia status. More-sensitive PPTs at sites over or distant from joints were each associated with greater reported pain, higher patient-reported DAS28 components, and poorer mental health. A high proportion of participants (48%) satisfied classification criteria for fibromyalgia, and fibromyalgia classification or characteristics were each associated with more sensitive PPTs, higher patient-reported DAS28 components, and poorer mental health. Widespread sensitivity to pressure-induced pain, a high prevalence of fibromyalgic features, higher patient-reported DAS28 components, and poorer mental health are all linked in established RA. The increased sensitivity at nonjoint sites (sternum and anterior tibia), as well as over joints, indicates that central mechanisms may contribute to pain sensitivity in RA. The contribution of patient-reported components to high DAS28 should inform decisions on disease-modifying or pain-management approaches in the treatment of RA when inflammation may be well controlled.

Machine-learned analysis of quantitative sensory testing responses to noxious cold stimulation in healthy subjects.

PubMed

Weyer-Menkhoff, I; Thrun, M C; Lötsch, J

2018-05-01

Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers. The probability density distribution was analysed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM), emergent self-organizing maps and self-organizing swarms of data agents. The probability density function of pain responses was trimodal (mean thresholds at 25.9, 18.4 and 8.0 °C for tonic and 24.5, 18.1 and 7.5 °C for phasic stimuli). Subjects' association with Gaussian modes was consistent between both types of stimuli (weighted Cohen's κ = 0.91). Patterns emerging in self-organizing neuronal maps and swarms could be associated with different trends towards decreasing cold pain sensitivity in different Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as particularly distinct. Thresholds at, roughly, 25 and 18 °C agree with known working temperatures of TRPM8 and TRPA1 ion channels, respectively, and hint at relative local dominance of either channel in respective subjects. Data patterns suggest involvement of further distinct mechanisms in cold pain perception at lower temperatures. Findings support data science approaches to identify biologically plausible hints at complex molecular mechanisms underlying human pain phenotypes. Sensitivity to pain is heterogeneous. Data-driven computational research approaches allow the identification of subgroups of subjects with a distinct pattern of sensitivity to cold stimuli. The subgroups are reproducible with different types of noxious cold stimuli. Subgroups show pattern that hints at distinct and inter-individually different types of the underlying molecular background. © 2018 European Pain Federation - EFIC®.

A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect

PubMed Central

Chang, Luke J.; Gianaros, Peter J.; Manuck, Stephen B.; Krishnan, Anjali; Wager, Tor D.

2015-01-01

Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high–low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion–pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional “emotion-related” regions (e.g., amygdala, insula) or resting-state networks (e.g., “salience,” “default mode”). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes. PMID:26098873

Novel insights on diagnosis, cause and treatment of diabetic neuropathy: focus on painful diabetic neuropathy

PubMed Central

Tavakoli, Mitra; Asghar, Omar; Alam, Uazman; Petropoulos, Ioannis N.; Fadavi, Hassan; Malik, Rayaz A.

2010-01-01

Diabetic neuropathy is common, under or misdiagnosed, and causes substantial morbidity with increased mortality. Defining and developing sensitive diagnostic tests for diabetic neuropathy is not only key to implementing earlier interventions but also to ensure that the most appropriate endpoints are employed in clinical intervention trials. This is critical as many potentially effective therapies may never progress to the clinic, not due to a lack of therapeutic effect, but because the endpoints were not sufficiently sensitive or robust to identify benefit. Apart from improving glycaemic control, there is no licensed treatment for diabetic neuropathy, however, a number of pathogenetic pathways remain under active study. Painful diabetic neuropathy is a cause of considerable morbidity and whilst many pharmacological and nonpharmacological interventions are currently used, only two are approved by the US Food and Drug Administration. We address the important issue of the ‘placebo effect’ and also consider potential new pharmacological therapies as well as nonpharmacological interventions in the treatment of painful diabetic neuropathy. PMID:23148152

Sincerity of effort versus feigned movement control of the cervical spine in patients with whiplash-associated disorders and asymptomatic persons: a case-control study.

PubMed

Oddsdóttir, Gudny Lilja; Kristjansson, Eythor; Gislason, Magnus Kjartan

2015-01-01

Cross-sectional design. To investigate whether the Fly Test can be used to differentiate patients with whiplash-associated disorders (WAD) from asymptomatic persons who deliberately feign symptoms and from WAD patients exaggerating symptoms. The lack of valid clinical tests makes it difficult to detect a justifiable cause for compensation claims in traumatic neck-pain disorders. The Fly Test recorded the accuracy of neck movements in patients with WAD (n = 34) and asymptomatic persons (n = 31). The participants followed a moving "Fly" on a computer screen with a cursor from sensors mounted on the head. Two conditions were tested, sincere versus feigned efforts. In the former, the participants moved their neck as accurately as possible. In the latter, a short text was presented describing a fictitious accident (asymptomatic group) or imagining more intense pain/suffering (WAD group), and the test was performed as affected by these more serious conditions. Amplitude accuracy (AA), time on target (ToT) and jerk index (JI) were compared across patterns, conditions and groups. The sincere effort in the WAD group was significant compared to the feigned effort of the asymptomatic group (p < 0.001). For AA, correct categorization of 81.5% of the performances was made, where a mean score above 5.5 mm differentiated feigned versus sincere efforts in asymptomatic and WAD groups (sensitivity 79.4%, specificity 67.7%). For ToT, score above 11% indicated correctly categorized WAD patients (sensitivity 82.4%, specificity 64.5%). The Fly Test can provide clinicians a clue when patients with mild to moderate pain/disability are feigning or exaggerating symptoms.

Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.

PubMed

Younger, Jarred; Mackey, Sean

2009-01-01

Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial, we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia. Participants completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks). Ten women meeting criteria for fibromyalgia and not taking an opioid medication. Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation. Participants completed reports of symptom severity everyday, using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity. Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone. We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.

Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

PubMed

Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

2013-10-01

Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

Mindfulness Meditation and Cognitive Behavioral Therapy Intervention Reduces Pain Severity and Sensitivity in Opioid-Treated Chronic Low Back Pain: Pilot Findings from a Randomized Controlled Trial.

PubMed

Zgierska, Aleksandra E; Burzinski, Cindy A; Cox, Jennifer; Kloke, John; Stegner, Aaron; Cook, Dane B; Singles, Janice; Mirgain, Shilagh; Coe, Christopher L; Bačkonja, Miroslav

2016-10-01

To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). Outpatient. Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen's d = 0.86), and decreased pain sensitivity to thermal stimuli (P < 0.05), without adverse events. Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits. Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Women experience greater heat pain adaptation and habituation than men.

PubMed

Hashmi, Javeria A; Davis, Karen D

2009-10-01

It is not clear how males and females cope with pain over time and how sensory and emotional qualities fluctuate from moment to moment, although studies of pain at discrete time points suggest that women are more pain sensitive than men. Therefore, we developed a new broader-based pain model that incorporates a temporally continuous assessment of multiple pain dimensions across sensory and affective dimensions, and normalized peak pain intensity to unmask sex differences that may otherwise be confounded by inter-individual variability in pain sensitivity. We obtained continuous ratings of pain, burning, sharp, stinging, cutting, and annoyance evoked by repeated prolonged noxious heat stimuli in 32 subjects. Strikingly, females reported more pain than males at the outset of the first exposure to pain, but then experienced less pain and annoyance than males as a painful stimulus was sustained and with repeated stimulation. Patterns of pain and annoyance attenuation in women resembled the attenuation of sharp, stinging and cutting sensations, whereas patterns of pain and annoyance in men resembled burning sensations. Taken together, these data demonstrate a prominent sex difference in the time course of pain. Notably only females demonstrate adaptation and habituation that allow them to experience less pain over time. These findings suggest a sexual dichotomy in mechanisms underlying pain intensity and annoyance that could involve specific quality-linked mechanisms. Importantly, temporal processing of pain differs between males and females when adjusted for sex differences in pain sensitivity. Our findings provide insight into sex differences in tonic and possibly chronic pains.

Sex differences in antinociceptive response to Δ-9-tetrahydrocannabinol and CP 55,940 in the mouse formalin test.

PubMed

LaFleur, Rebecca A; Wilson, Ronald P; Morgan, Daniel J; Henderson-Redmond, Angela N

2018-04-11

Cannabinoids have shown promise for the treatment of intractable pain states and may represent an alternative pharmacotherapy for pain management. A growing body of clinical evidence suggests a role for sex in pain perception and in cannabinoid response. We examined cannabinoid sensitivity and tolerance in male and female mice expressing a desensitization-resistant form (S426A/S430A) of the cannabinoid type 1 receptor (CB1R). Mice were assessed for acute and inflammatory nociceptive behaviors in the formalin test following pretreatment with either vehicle or mixed CB1R/CB2R agonists, Δ-9-tetrahydrocannabinol ([INCREMENT]-THC) (1-6 mg/kg) or CP 55,940 (0.06-0.2 mg/kg). Tolerance to the effects of 6 mg/kg [INCREMENT]-THC or 0.1 mg/kg CP 55,940 was examined by the formalin test following chronic daily dosing. Female mice showed decreased sensitivity to the effects of [INCREMENT]-THC and CP 55,940 compared with male mice. The S426A/S430A mutation increased the attenuation of nociceptive behaviors for both agonists in both sexes. Female mice displayed delayed tolerance to [INCREMENT]-THC compared with male mice, whereas the S426A/S430A mutation conferred a delay in tolerance to [INCREMENT]-THC in both sexes. Male S426A/S430A mutant mice also display resistance to tolerance to CP 55,940 compared with wild-type controls. This study demonstrates sex and genotype differences in response for two different cannabinoid agonists. The results underscore the importance of including both male and female mice in preclinical studies of pain and cannabinoid pharmacology.

The optimal imaging strategy for patients with stable chest pain: a cost-effectiveness analysis.

PubMed

Genders, Tessa S S; Petersen, Steffen E; Pugliese, Francesca; Dastidar, Amardeep G; Fleischmann, Kirsten E; Nieman, Koen; Hunink, M G Myriam

2015-04-07

The optimal imaging strategy for patients with stable chest pain is uncertain. To determine the cost-effectiveness of different imaging strategies for patients with stable chest pain. Microsimulation state-transition model. Published literature. 60-year-old patients with a low to intermediate probability of coronary artery disease (CAD). Lifetime. The United States, the United Kingdom, and the Netherlands. Coronary computed tomography (CT) angiography, cardiac stress magnetic resonance imaging, stress single-photon emission CT, and stress echocardiography. Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. The strategy that maximized QALYs and was cost-effective in the United States and the Netherlands began with coronary CT angiography, continued with cardiac stress imaging if angiography found at least 50% stenosis in at least 1 coronary artery, and ended with catheter-based coronary angiography if stress imaging induced ischemia of any severity. For U.K. men, the preferred strategy was optimal medical therapy without catheter-based coronary angiography if coronary CT angiography found only moderate CAD or stress imaging induced only mild ischemia. In these strategies, stress echocardiography was consistently more effective and less expensive than other stress imaging tests. For U.K. women, the optimal strategy was stress echocardiography followed by catheter-based coronary angiography if echocardiography induced mild or moderate ischemia. Results were sensitive to changes in the probability of CAD and assumptions about false-positive results. All cardiac stress imaging tests were assumed to be available. Exercise electrocardiography was included only in a sensitivity analysis. Differences in QALYs among strategies were small. Coronary CT angiography is a cost-effective triage test for 60-year-old patients who have nonacute chest pain and a low to intermediate probability of CAD. Erasmus University Medical Center.

Pain Threshold Tests in Patients With Heel Pain Syndrome.

PubMed

Saban, Bernice; Masharawi, Youssef

2016-07-01

Pressure pain threshold (PPT) is a useful tool for evaluating mechanical sensitivity in patients suffering from various musculoskeletal disorders. However, no previous study has investigated PPT in the heel of patients experiencing plantar heel pain syndrome (PHPS). The aim of this study was to compare PPT levels and topographic presentation of sensitivity in the heel of patients with PHPS and in healthy controls. The reliability of PPT testing in patients with PHPS was assessed for intra- and interrater recordings. The PPT levels of 40 feet in each group were then assessed on 5 predetermined sites in the heel using a standardized measurement protocol. Patient functional status (FS) as measured by the Foot & Ankle Computerized Adaptive Test was employed as an external reference. Multivariate analysis of covariance revealed no group differences for PPTs at all sites (P = .406). Age (P = .099) or BMI (P = .510) did not affect PPT values, although there was an effect on gender (P = .006). The analysis revealed significant differences between sites (P < .001) demonstrating a diverse topographic distribution. In the PHPS group, PPT levels at the anterior/medial, posterior/medial and central sites were significantly lower than at the posterior/lateral and anterior/lateral sites (P < .05). For the control group, PPT levels at the anterior/medial site were significantly lower than all other sites (P < .001). No significant differences were found between PPT of the PHPS patients and controls, therefore, PPT cannot be recommended as an assessment tool for these patients. The topographic distribution indicated low PPT levels at the anterior/medial area of the heel in patients with PHPS and controls. Level II, comparative study. © The Author(s) 2016.

Accuracy of gestalt perception of acute chest pain in predicting coronary artery disease

PubMed Central

das Virgens, Cláudio Marcelo Bittencourt; Lemos Jr, Laudenor; Noya-Rabelo, Márcia; Carvalhal, Manuela Campelo; Cerqueira Junior, Antônio Maurício dos Santos; Lopes, Fernanda Oliveira de Andrade; de Sá, Nicole Cruz; Suerdieck, Jéssica Gonzalez; de Souza, Thiago Menezes Barbosa; Correia, Vitor Calixto de Almeida; Sodré, Gabriella Sant'Ana; da Silva, André Barcelos; Alexandre, Felipe Kalil Beirão; Ferreira, Felipe Rodrigues Marques; Correia, Luís Cláudio Lemos

2017-01-01

AIM To test accuracy and reproducibility of gestalt to predict obstructive coronary artery disease (CAD) in patients with acute chest pain. METHODS We studied individuals who were consecutively admitted to our Chest Pain Unit. At admission, investigators performed a standardized interview and recorded 14 chest pain features. Based on these features, a cardiologist who was blind to other clinical characteristics made unstructured judgment of CAD probability, both numerically and categorically. As the reference standard for testing the accuracy of gestalt, angiography was required to rule-in CAD, while either angiography or non-invasive test could be used to rule-out. In order to assess reproducibility, a second cardiologist did the same procedure. RESULTS In a sample of 330 patients, the prevalence of obstructive CAD was 48%. Gestalt’s numerical probability was associated with CAD, but the area under the curve of 0.61 (95%CI: 0.55-0.67) indicated low level of accuracy. Accordingly, categorical definition of typical chest pain had a sensitivity of 48% (95%CI: 40%-55%) and specificity of 66% (95%CI: 59%-73%), yielding a negligible positive likelihood ratio of 1.4 (95%CI: 0.65-2.0) and negative likelihood ratio of 0.79 (95%CI: 0.62-1.02). Agreement between the two cardiologists was poor in the numerical classification (95% limits of agreement = -71% to 51%) and categorical definition of typical pain (Kappa = 0.29; 95%CI: 0.21-0.37). CONCLUSION Clinical judgment based on a combination of chest pain features is neither accurate nor reproducible in predicting obstructive CAD in the acute setting. PMID:28400920

Spinal Manipulative Therapy Has an Immediate Effect on Thermal Pain Sensitivity in People With Low Back Pain: A Randomized Controlled Trial

PubMed Central

Bishop, Mark D.; Robinson, Michael E.; Zeppieri, Giorgio; George, Steven Z.

2009-01-01

Background Current evidence suggests that spinal manipulative therapy (SMT) is effective in the treatment of people with low back pain (LBP); however, the corresponding mechanisms are unknown. Hypoalgesia is associated with SMT and is suggestive of specific mechanisms. Objective The primary purpose of this study was to assess the immediate effects of SMT on thermal pain perception in people with LBP. A secondary purpose was to determine whether the resulting hypoalgesia was a local effect and whether psychological influences were associated with changes in pain perception. Design This study was a randomized controlled trial. Setting A sample of convenience was recruited from community and outpatient clinics. Participants Thirty-six people (10 men, 26 women) currently experiencing LBP participated in the study. The average age of the participants was 32.39 (SD=12.63) years, and the average duration of LBP was 221.79 (SD=365.37) weeks. Intervention and Measurements Baseline demographic and psychological measurements were obtained, followed by quantitative sensory testing to assess temporal summation and Aδ fiber–mediated pain perception. Next, participants were randomly assigned to ride a stationary bicycle, perform low back extension exercises, or receive SMT. Finally, the same quantitative sensory testing protocol was reassessed to determine the immediate effects of each intervention on thermal pain sensitivity. Results Hypoalgesia to Aδ fiber–mediated pain perception was not observed. Group-dependent hypoalgesia of temporal summation specific to the lumbar innervated region was observed. Pair-wise comparisons indicated significant hypoalgesia in participants who received SMT, but not in those who rode a stationary bicycle or performed low back extension exercises. Psychological factors did not significantly correlate with changes in temporal summation in participants who received SMT. Limitations Only immediate effects of SMT were measured, so the authors are unable to comment on whether the inhibition of temporal summation is a lasting effect. Furthermore, the authors are unable to comment on the relationship between their findings and changes in clinical pain. Conclusions Inhibition of Aδ fiber–mediated pain perception was similar for all groups. However, inhibition of temporal summation was observed only in participants receiving SMT, suggesting a modulation of dorsal horn excitability that was observed primarily in the lumbar innervated area. PMID:19797305

Total pancreatectomy for recurrent acute and chronic pancreatitis: a critical review of patient selection criteria

PubMed Central

Faghih, Mahya; Gonzalez, Francisco Garcia; Makary, Martin A.; Singh, Vikesh K.

2018-01-01

Purpose of review Critical review of the indications for total pancreatectomy and highlight limitations in current diagnostic criteria for chronic pancreatitis. Recent findings The diagnosis of noncalcific chronic pancreatitis remains controversial because of an overreliance on nonspecific imaging and laboratories findings. Endoscopic ultrasound, s-magnetic resonance cholangiopancreatography, and/or endoscopic pancreatic function testing are often used to diagnose noncalcific chronic pancreatitis despite the fact that there is no gold standard for this condition. Abdominal pain is not specific for chronic pancreatitis and is more likely to be encountered in patients with functional gastrointestinal disorders based on the high incidence of these conditions. The duration of pain and opioid analgesic use results in central sensitization that adversely affects pain outcomes after total pancreatectomy. An alcoholic cause is associated with poorer pain outcomes after total pancreatectomy. Summary The lack of a gold standard for noncalcific chronic pancreatitis limits the diagnostic accuracy of imaging and laboratory tests. The pain of chronic pancreatitis is nonspecific and is affected by duration, preoperative opioid use, and cause. These factors will need to be considered in the development of future selection criteria for this morbid surgery. PMID:28700371

The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice.

PubMed

Wang, Weijie; Yu, Yingcong; Li, Jing; Wang, Lin; Li, Zhi; Zhang, Chong; Zhen, Linlin; Ding, Lianshu; Wang, Gang; Sun, Xiaoyang; Xu, Ying

2017-08-01

Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca 2+ /calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca 2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl 2 , ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca 2+ , however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl 2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.

The MNK–eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain

PubMed Central

Asiedu, Marina N.; Megat, Salim; Burton, Michael D.; Burgos-Vega, Carolina C.; Melemedjian, Ohannes K.; Boitano, Scott; Vagner, Josef; Pancrazio, Joseph J.; Mogil, Jeffrey S.; Dussor, Gregory

2017-01-01

Injury-induced sensitization of nociceptors contributes to pain states and the development of chronic pain. Inhibiting activity-dependent mRNA translation through mechanistic target of rapamycin and mitogen-activated protein kinase (MAPK) pathways blocks the development of nociceptor sensitization. These pathways convergently signal to the eukaryotic translation initiation factor (eIF) 4F complex to regulate the sensitization of nociceptors, but the details of this process are ill defined. Here we investigated the hypothesis that phosphorylation of the 5′ cap-binding protein eIF4E by its specific kinase MAPK interacting kinases (MNKs) 1/2 is a key factor in nociceptor sensitization and the development of chronic pain. Phosphorylation of ser209 on eIF4E regulates the translation of a subset of mRNAs. We show that pronociceptive and inflammatory factors, such as nerve growth factor (NGF), interleukin-6 (IL-6), and carrageenan, produce decreased mechanical and thermal hypersensitivity, decreased affective pain behaviors, and strongly reduced hyperalgesic priming in mice lacking eIF4E phosphorylation (eIF4ES209A). Tests were done in both sexes, and no sex differences were found. Moreover, in patch-clamp electrophysiology and Ca2+ imaging experiments on dorsal root ganglion neurons, NGF- and IL-6-induced increases in excitability were attenuated in neurons from eIF4ES209A mice. These effects were recapitulated in Mnk1/2−/− mice and with the MNK1/2 inhibitor cercosporamide. We also find that cold hypersensitivity induced by peripheral nerve injury is reduced in eIF4ES209A and Mnk1/2−/− mice and following cercosporamide treatment. Our findings demonstrate that the MNK1/2–eIF4E signaling axis is an important contributing factor to mechanisms of nociceptor plasticity and the development of chronic pain. SIGNIFICANCE STATEMENT Chronic pain is a debilitating disease affecting approximately one in three Americans. Chronic pain is thought to be driven by changes in the excitability of peripheral nociceptive neurons, but the precise mechanisms controlling these changes are not elucidated. Emerging evidence demonstrates that mRNA translation regulation pathways are key factors in changes in nociceptor excitability. Our work demonstrates that a single phosphorylation site on the 5′ cap-binding protein eIF4E is a critical mechanism for changes in nociceptor excitability that drive the development of chronic pain. We reveal a new mechanistic target for the development of a chronic pain state and propose that targeting the upstream kinase, MAPK interacting kinase 1/2, could be used as a therapeutic approach for chronic pain. PMID:28674170

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

PubMed Central

Carroll, C. Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469

Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis.

PubMed

Olesen, Anne E; Nielsen, Lecia M; Feddersen, Søren; Erlenwein, Joachim; Petzke, Frank; Przemeck, Michael; Christrup, Lona L; Drewes, Asbjørn M

2018-06-01

Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu, kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned pain modulation effect, and (4) pressure stimulation at the tibia in both the affected and the unaffected leg. Ninety-two patients (mean age 66 years) with unilateral hip osteoarthritis were included in the study. Carriage of the OPRM1 rs589046T allele was found to be associated with increased pain ratings during hip rotation (P = 0.04) and increased conditioned pain modulation (P = 0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with an increased pain detection threshold to contact heat stimulation (P = 0.001). No other associations were found (all P > 0.05). Results from the present study suggest that, in patients with hip osteoarthritis, genetic variants in OPRM1 and OPRD1 may contribute to the pain phenotype. © 2017 World Institute of Pain.

Effect profile of paracetamol, Δ9-THC and promethazine using an evoked pain test battery in healthy subjects.

PubMed

van Amerongen, G; Siebenga, P; de Kam, M L; Hay, J L; Groeneveld, G J

2018-04-10

A battery of evoked pain tasks (PainCart) was developed to investigate the pharmacodynamic properties of novel analgesics in early-phase clinical research. As part of its clinical validation, compounds with different pharmacological mechanisms of actions are investigated. The aim was to investigate the analgesic effects of classic and nonclassic analgesics compared to a sedating negative control in a randomized placebo-controlled crossover study in 24 healthy volunteers using the PainCart. The PainCart consisted of pain tasks eliciting electrical, pressure, heat, cold and inflammatory pain. Subjective scales for cognitive functioning and psychotomimetic effects were included. Subjects were administered each of the following oral treatments: paracetamol (1000 mg), Δ9-THC (10 mg), promethazine (50 mg) or matching placebo. Pharmacodynamic measurements were performed at baseline and repeated up to 10 h postdose. Paracetamol did not show a significant reduction in pain sensation or subjective cognitive functioning compared to placebo. Promethazine induced a statistically significant reduction in PTT for cold pressor and pressure stimulation. Furthermore, reduced subjective alertness was observed. Δ9-THC showed a statistically significant decrease in PTT for electrical and pressure stimulation. Δ9-THC also demonstrated subjective effects, including changes in alertness and calmness, as well as feeling high and psychotomimetic effects. This study found a decreased pain tolerance due to Δ9-THC and promethazine, or lack thereof, using an evoked pain task battery. Pain thresholds following paracetamol administration remained unchanged, which may be due to insufficient statistical power. We showed that pain thresholds determined using this pain test battery are not driven by sedation. The multimodal battery of evoked pain tasks utilized in this study may play an important role in early-phase clinical drug development. This battery of pain tasks is not sensitive to the effects of sedation alone, and thus suitable to investigate the analgesic potential of novel analgesic compounds. © 2018 European Pain Federation - EFIC®.

Sex differences and hormonal modulation of deep tissue pain

PubMed Central

Traub, Richard J.; Ji, Yaping

2013-01-01

Women disproportionately suffer from many deep tissue pain conditions. Experimental studies show that women have lower pain thresholds, higher pain ratings and less tolerance to a range of painful stimuli. Most clinical and epidemiological reports suggest female gonadal hormones modulate pain for some, but not all, conditions. Similarly, animal studies support greater nociceptive sensitivity in females in many deep tissue pain models. Gonadal hormones modulate responses in primary afferents, dorsal horn neurons and supraspinal sites, but the direction of modulation is variable. This review will examine sex differences in deep tissue pain in humans and animals focusing on the role of gonadal hormones (mainly estradiol) as an underlying component of the modulation of pain sensitivity. PMID:23872333

Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome

PubMed Central

Meeus, Mira

2006-01-01

In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS. This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc. PMID:17115100

Reliability and diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar nerve root compression: a pilot study.

PubMed

Trainor, Kate; Pinnington, Mark A

2011-03-01

It has been proposed that neurodynamic examination can assist differential diagnosis of upper/mid lumbar nerve root compression; however, the diagnostic validity of many of these tests has yet to be established. This pilot study aimed to establish the diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar nerve root compression in subjects with suspected lumbosacral radicular pain. Two independent examiners performed the slump knee bend test on subjects with radicular leg pain. Inter-tester reliability was calculated using the kappa coefficient. Slump knee bend test results were compared with magnetic resonance imaging findings, and diagnostic accuracy measures were calculated including sensitivity, specificity, predictive values and likelihood ratios. Orthopaedic spinal clinic, secondary care. Sixteen patients with radicular leg pain. All four subjects with mid lumbar nerve root compression on magnetic resonance imaging were correctly identified with the slump knee bend test; however, it was falsely positive in two individuals without the condition. Inter-tester reliability for the slump knee bend test using the kappa coefficient was 0.71 (95% confidence interval 0.33 to 1.0). Diagnostic validity calculations for the slump knee bend test (95% confidence intervals) were: sensitivity, 100% (40 to 100%); specificity, 83% (52 to 98%); positive predictive value, 67% (22 to 96%); negative predictive value, 100% (69 to 100%); positive likelihood ratio, 6.0 (1.58 to 19.4); and negative likelihood ratio, 0 (0 to 0.6). Results indicate good inter-tester reliability and suggest that the slump knee bend test has potential to be a useful clinical test for identifying patients with mid lumbar nerve root compression. Further investigation is needed on larger numbers of patients to confirm these findings. Copyright © 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

The Sensitivity to Change and Responsiveness of the Adult Responses to Children’s Symptoms in Children and Adolescents With Chronic Pain

PubMed Central

Alberts, Nicole; Langer, Shelby L.; Levy, Rona L.; Walker, Lynn S.; Palermo, Tonya M.

2016-01-01

Abstract Objective  To examine the sensitivity to change and responsiveness of the Adult Responses to Children’s Symptoms (ARCS) among parents of youth with chronic pain.  Methods  Participants included 330 youth (89 children aged 7–11 years, 241 children aged 12–17 years) and their parents who participated in randomized controlled trials of family-based cognitive-behavioral therapy for chronic pain. Child pain and disability, parental emotional functioning, and parental responses to child pain were assessed at baseline and posttreatment.  Results  The Protect and Monitor scales of the ARCS were sensitive to change following intervention for both developmental groups, with clinically meaningful reductions in these behaviors, thereby demonstrating responsiveness. Among the adolescent sample, greater change on some ARCS scales was associated with better parental emotional functioning and lower child pain at posttreatment.  Conclusions  Findings support the sensitivity to change and responsiveness of the Protect and Monitor scales among parents of youth with chronic pain. PMID:26493601

Increased pain sensitivity but normal function of exercise induced analgesia in hip and knee osteoarthritis--treatment effects of neuromuscular exercise and total joint replacement.

PubMed

Kosek, E; Roos, E M; Ageberg, E; Nilsdotter, A

2013-09-01

To assess exercise induced analgesia (EIA) and pain sensitivity in hip and knee osteoarthritis (OA) and to study the effects of neuromuscular exercise and surgery on these parameters. The dataset consisted of knee (n = 66) and hip (n = 47) OA patients assigned for total joint replacement at Lund University Hospital undergoing pre-operative neuromuscular exercise and 43 matched controls. Sensitivity to pressure pain was assessed by pressure algometry at 10 sites. Subjects were then instructed to perform a standardized static knee extension. Pressure pain thresholds (PPTs) were assessed at the contracting quadriceps muscle (Q) and at the resting deltoid muscle (D) before and during contraction. The relative increase in PPTs during contraction was taken as a measure of localized (Q) or generalized (D) EIA. Patients were assessed at baseline, following on average 12 weeks of neuromuscular exercise and 3 months following surgery. We found a normal function of EIA in OA patients at baseline. Previous studies have reported beneficial effects of physical exercise on pain modulation in healthy subjects. However, no treatment effects on EIA were seen in OA patients despite the increase in muscle strength following neuromuscular exercise and reduced pain following surgery. Compared to controls, OA patients had increased pain sensitivity and no beneficial effects on pain sensitivity were seen following treatment. To our knowledge, this is the first study of EIA in OA patients. Despite increased pain sensitivity, OA patients had a normal function of EIA. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Musculoskeletal sensitization and sleep: chronic muscle pain fragments sleep of mice without altering its duration.

PubMed

Sutton, Blair C; Opp, Mark R

2014-03-01

Musculoskeletal pain in humans is often associated with poor sleep quality. We used a model in which mechanical hypersensitivity was induced by injection of acidified saline into muscle to study the impact of musculoskeletal sensitization on sleep of mice. A one month pre-clinical study was designed to determine the impact of musculoskeletal sensitization on sleep of C57BL/6J mice. We instrumented mice with telemeters to record the electroencephalogram (EEG) and body temperature. We used an established model of musculoskeletal sensitization in which mechanical hypersensitivity was induced using two unilateral injections of acidified saline (pH 4.0). The injections were given into the gastrocnemius muscle and spaced five days apart. EEG and body temperature recordings started prior to injections (baseline) and continued for three weeks after musculoskeletal sensitization was induced by the second injection. Mechanical hypersensitivity was assessed using von Frey filaments at baseline (before any injections) and on days 1, 3, 7, 14, and 21 after the second injection. Mice injected with acidified saline developed bilateral mechanical hypersensitivity at the hind paws as measured by von Frey testing and as compared to control mice and baseline data. Sleep during the light period was fragmented in experimental mice injected with acidified saline, and EEG spectra altered. Musculoskeletal sensitization did not alter the duration of time spent in wakefulness, non-rapid eye movement sleep, or rapid eye movement sleep. Musculoskeletal sensitization in this model results in a distinct sleep phenotype in which sleep is fragmented during the light period, but the overall duration of sleep is not changed. This study suggests the consequences of musculoskeletal pain include sleep disruption, an observation that has been made in the clinical literature but has yet to be studied using preclinical models.

Decreased alertness due to sleep loss increases pain sensitivity in mice

PubMed Central

Alexandre, Chloe; Latremoliere, Alban; Ferreira, Ashley; Miracca, Giulia; Yamamoto, Mihoko; Scammell, Thomas E; Woolf, Clifford J

2018-01-01

Extended daytime and nighttime activities are major contributors to the growing sleep deficiency epidemic1,2, as is the high prevalence of sleep disorders like insomnia. The consequences of chronic insufficient sleep for health remain uncertain3. Sleep quality and duration predict presence of pain the next day in healthy subjects4–7, suggesting that sleep disturbances alone may worsen pain, and experimental sleep deprivation in humans supports this claim8,9. We demonstrate that sleep loss, but not sleep fragmentation, in healthy mice increases sensitivity to noxious stimuli (referred to as ‘pain’) without general sensory hyper-responsiveness. Moderate daily repeated sleep loss leads to a progressive accumulation of sleep debt and also to exaggerated pain responses, both of which are rescued after restoration of normal sleep. Caffeine and modafinil, two wake-promoting agents that have no analgesic activity in rested mice, immediately normalize pain sensitivity in sleep-deprived animals, without affecting sleep debt. The reversibility of mild sleep-loss-induced pain by wake-promoting agents reveals an unsuspected role for alertness in setting pain sensitivity. Clinically, insufficient or poor-quality sleep may worsen pain and this enhanced pain may be reduced not by analgesics, whose effectiveness is reduced, but by increasing alertness or providing better sleep. PMID:28481358

Improved foot sensitivity and pain reduction in patients with peripheral neuropathy after treatment with monochromatic infrared photo energy--MIRE.

PubMed

Harkless, Lawrence B; DeLellis, Salvatore; Carnegie, Dale H; Burke, Thomas J

2006-01-01

The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated.

Mindfulness Meditation and Cognitive Behavioral Therapy Intervention Reduces Pain Severity and Sensitivity in Opioid-Treated Chronic Low Back Pain: Pilot Findings from a Randomized Controlled Trial

PubMed Central

Burzinski, Cindy A.; Cox, Jennifer; Kloke, John; Stegner, Aaron; Cook, Dane B.; Singles, Janice; Mirgain, Shilagh; Coe, Christopher L.; Bačkonja, Miroslav

2016-01-01

Objective. To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). Design. 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). Setting. Outpatient. Subjects. Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. Methods. The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). Results. Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen’s d = 0.86), and decreased pain sensitivity to thermal stimuli (P < 0.05), without adverse events. Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits. Conclusions. Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP. PMID:26968850

Reliability and validity of three pain provocation tests used for the diagnosis of chronic proximal hamstring tendinopathy.

PubMed

Cacchio, Angelo; Borra, Fabrizio; Severini, Gabriele; Foglia, Andrea; Musarra, Frank; Taddio, Nicola; De Paulis, Fosco

2012-09-01

The clinical assessment of chronic proximal hamstring tendinopathy (PHT) in athletes is a challenge to sports medicine. To be able to compare the results of research and treatments, the methods used to diagnose and evaluate PHT must be clearly defined and reproducible. To assess the reliability and validity of three pain provocation tests used for the diagnosis of PHT. Ninety-two athletes with (N=46) and without (N=46) PHT were examined by one physician and two physiotherapists, who were trained in the examination techniques before the study. The examiners were blinded to the symptoms and identity of the athletes. The three pain provocation tests examined were the Puranen-Orava, bent-knee stretch and modified bent-knee stretch tests. Intraclass correlation coefficients (ICCs) based on the repeated measures analysis of variance were used to analyse the intraexaminer and interexaminer reliability, while sensitivity, specificity, predictive values and likelihood ratios were used to determine the validity of the three tests. The ICC values in all three tests revealed a high correlation (range 0.82 to 0.88) for the interexaminer reliability and a high-to-very high correlation (range 0.87 to 0.93) for the intraexaminer reliability. All three tests displayed a moderate-to-high validity, with the highest degree of validity being yielded by the modified bent-knee stretch test. All three pain provocation tests proved to be of potential value in assessing chronic PHT in athletes. However, we recommend that they be used in conjunction with other objective measures, such as MRI.

Systematic mechanism-orientated approach to chronic pancreatitis pain.

PubMed

Bouwense, Stefan A W; de Vries, Marjan; Schreuder, Luuk T W; Olesen, Søren S; Frøkjær, Jens B; Drewes, Asbjørn M; van Goor, Harry; Wilder-Smith, Oliver H G

2015-01-07

Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.

Sex-Specific Effects of Gender Identification on Pain Study Recruitment.

PubMed

Mattos Feijó, Larissa; Tarman, Guliz Zeynep; Fontaine, Charlotte; Harrison, Richard; Johnstone, Tom; Salomons, Tim

2018-02-01

Epidemiological, clinical, and laboratory studies show sex differences in pain responses, with women more sensitive to nociceptive stimulation and more vulnerable to long-term pain conditions than men. Because of evidence that men are culturally reinforced for the ability to endure (or under-report) pain, some of these findings might be explained by sociocultural beliefs about gender-appropriate behavior. One potential manifestation of these effects might be differential participation in pain studies, with men adhering to stereotypical masculine roles viewing participation as a way to demonstrate their masculinity. To test this possibility, we assessed gender identification in 137 healthy participants. At the end of the assessment, they were asked if they would like to participate in other research studies. Interested participants were then asked to participate in a study involving administration of pain-evoking stimulation. We compared individuals who agreed to participate in the pain study with those who declined. We observed a significant Sex × Participation interaction in masculine gender identification, such that men (but not women) who agreed to participate identified significantly more with masculine gender. Among masculine gender traits examined, we found that high levels of aggression and competitiveness were the strongest predictors of pain study participation. Our results suggest that men in pain studies might have higher levels of masculine gender identification than the wider male population. Taken together with previous findings of lower levels of pain sensitivity (or reporting) in masculine-identifying male participants, these results suggest an explanation for some of the sex-related differences observed in pain responses. To examine whether sex and gender affect willingness to participate in pain studies, we assessed gender identification in men and women, then attempted to recruit them to participate in a pain study. Men who agree to participate in pain studies are significantly higher in masculine gender identification than men who decline to participate or women who agree to participate. Men who agreed to participate were rated particularly high in aggressiveness and competitiveness. Copyright © 2018. Published by Elsevier Inc.

Disrupted Self-Perception in People With Chronic Low Back Pain. Further Evaluation of the Fremantle Back Awareness Questionnaire.

PubMed

Wand, Benedict Martin; Catley, Mark Jon; Rabey, Martin Ian; O'Sullivan, Peter Bruce; O'Connell, Neil Edward; Smith, Anne Julia

2016-09-01

Several lines of evidence suggest that body perception is altered in people with chronic back pain. Maladaptive perceptual awareness of the back might contribute to the pain experience as well as serve as a target for treatment. The Fremantle Back Awareness Questionnaire (FreBAQ) is a simple questionnaire recently developed to assess back-specific altered self-perception. The aims of this study were to present the outcomes of a comprehensive evaluation of the questionnaire's psychometric properties and explore the potential relationships between body perception, nociceptive sensitivity, distress, and beliefs about back pain and the contribution these factors might play in explaining pain and disability. Two hundred fifty-one people with chronic back pain completed the questionnaire as well as a battery of clinical tests. The Rasch model was used to explore the questionnaires' psychometric properties and correlation and multiple linear regression analyses were used to explore the relationship between altered body perception and clinical status. The FreBAQ appears unidimensional with no redundant items, has minimal ceiling and floor effects, acceptable internal consistency, was functional on the category rating scale, and was not biased by demographic or clinical variables. FreBAQ scores were correlated with sensitivity, distress, and beliefs and were uniquely associated with pain and disability. Several lines of evidence suggest that body perception might be disturbed in people with chronic low back pain, possibly contributing to the condition and offering a potential target for treatment. The FreBAQ was developed as a quick and simple way of measuring back-specific body perception in people with chronic low back pain. The questionnaire appears to be a psychometrically sound way of assessing altered self-perception. The level of altered self-perception is positively correlated with pain intensity and disability as well as showing associations with psychological distress, pain catastrophization, fear avoidance beliefs, and lumbar pressure pain threshold. In this sample, it appears that altered self-perception might be a more important determinant of clinical severity than psychological distress, pain catastrophization, fear avoidance beliefs, or lumbar pressure pain threshold. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Anxiety and depressive symptoms and anxiety sensitivity in youngsters with noncardiac chest pain and benign heart murmurs.

PubMed

Lipsitz, Joshua D; Masia-Warner, Carrie; Apfel, Howard; Marans, Zvi; Hellstern, Beth; Forand, Nicholas; Levenbraun, Yosef; Fyer, Abby J

2004-12-01

Chest pain in children and adolescents is rarely associated with cardiac disease. We sought to examine psychological symptoms in youngsters with medically unexplained chest pain. We hypothesized that children and adolescents with medically unexplained chest pain would have high rates of anxiety and depressive symptoms. We assessed 65 youngsters with noncardiac chest pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self-report measures of anxiety and depressive symptoms and anxiety sensitivity. Compared with the asymptomatic benign-murmur group, youngsters with NCCP had higher levels of some anxiety symptoms and anxiety sensitivity. Differences on depressive symptoms were not significant. Though preliminary, results suggest that youngsters with chest pain may experience increased levels of some psychological symptoms. Future studies of noncardiac chest pain in youngsters should include larger samples and comprehensive diagnostic assessments as well as long-term follow-up evaluations.

A comprehensive review of opioid-induced hyperalgesia.

PubMed

Lee, Marion; Silverman, Sanford M; Hansen, Hans; Patel, Vikram B; Manchikanti, Laxmaiah

2011-01-01

Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or might be different from the original underlying pain. OIH appears to be a distinct, definable, and characteristic phenomenon that could explain loss of opioid efficacy in some patients. Findings of the clinical prevalence of OIH are not available. However, several observational, cross-sectional, and prospective controlled trials have examined the expression and potential clinical significance of OIH in humans. Most studies have been conducted using several distinct cohorts and methodologies utilizing former opioid addicts on methadone maintenance therapy, perioperative exposure to opioids in patients undergoing surgery, and healthy human volunteers after acute opioid exposure using human experimental pain testing. The precise molecular mechanism of OIH, while not yet understood, varies substantially in the basic science literature, as well as clinical medicine. It is generally thought to result from neuroplastic changes in the peripheral and central nervous system (CNS) that lead to sensitization of pronociceptive pathways. While there are many proposed mechanisms for OIH, 5 mechanisms involving the central glutaminergic system, spinal dynorphins, descending facilitation, genetic mechanisms, and decreased reuptake and enhanced nociceptive response have been described as the important mechanisms. Of these, the central glutaminergic system is considered the most common possibility. Another is the hypothesis that N-methyl-D-aspartate (NMDA) receptors in OIH include activation, inhibition of the glutamate transporter system, facilitation of calcium regulated intracellular protein kinase C, and cross talk of neural mechanisms of pain and tolerance. Clinicians should suspect OIH when opioid treatment's effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the original pain, and increased levels of pain with increasing dosages. The treatment involves reducing the opioid dosage, tapering them off, or supplementation with NMDA receptor modulators. This comprehensive review addresses terminology and definition, prevalence, the evidence for mechanism and physiology with analysis of various factors leading to OIH, and effective strategies for preventing, reversing, or managing OIH.

Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic noncancer pain.

PubMed

Markman, John D; Barbosa, William A; Gewandter, Jennifer S; Frazer, Maria; Rast, Shirley; Dugan, Michelle; Nandigam, Kiran; Villareal, Armando; Kwong, Tai C

2015-06-01

To determine whether the prevailing liquid chromatography and tandem mass spectroscopy assay (LC-MS/MS) assay designed to monitor buprenorphine compliance of the sublingual formulation used in the substance abuse treatment setting can be extrapolated to the transdermal formulation used in the chronic pain treatment setting, which is 1000-fold less concentrated. Retrospective chart review. Self-reported compliant patients using the transdermal or sublingual formulations of buprenorhphine. Transdermal patch application was also visually confirmed during clinic visits. Urine drug test results from a LC-MS/MS were compared between samples from transdermal and sublingual patients. While all sublingual patients tested positive for at least one metabolite of buprenorphine, only 69% of the transdermal patients did so. In addition, the most abundant metabolite in the transdermal patients was buprenorphine-glucuronide, as compared with norbuprenorphine-glucuronide in sublingual patients. These data suggest that currently available urine drug tests for buprenorphine, including the more expensive LC-MS/MS based assays, may not be sufficiently sensitive to detect the metabolites from transdermal buprenorphine patients. This study highlights the need to evaluate the value and sensitivity of urine drug tests given the wide range of buprenorphine dosing in clinical practice. These results underscore the need for additional cost benefit analyses comparing different confirmatory drug testing techniques including many commercially available drug testing options. © 2014 Wiley Periodicals, Inc. Wiley Periodicals, Inc.

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study.

PubMed

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas known to reflect the ongoing pain experience.

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study

PubMed Central

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas known to reflect the ongoing pain experience. PMID:27486748

A pilot study of myofascial release therapy compared to Swedish massage in fibromyalgia.

PubMed

Liptan, Ginevra; Mist, Scott; Wright, Cheryl; Arzt, Anna; Jones, Kim Dupree

2013-07-01

Fibromyalgia (FM) is characterized by widespread muscle pain and soft tissue tenderness. However, a lack of definitive muscle pathology has made FM both a diagnostic and a treatment puzzle. Much of the evidence for pathology in FM lies in the central nervous system - in particular abnormal amplification of pain signals in the spinal cord - a manifestation of central sensitization. An emerging body of evidence posits that peripheral pain generated from the muscles and fascia may trigger and maintain central sensitization in FM. Since FM patients so frequently seek manual therapy to relieve muscle symptoms, the present study compared two different manual therapy techniques in a parallel study of women with FM. Eight subjects received myofascial release (MFR) while four subjects received Swedish massage, 90 min weekly for four weeks. Overall symptom burden and physical function were assessed by the Fibromyalgia Impact Questionnaire Revised (FIQ-R). A unique challenge for the manual therapist in treating conditions involving central sensitization is to determine if localized pain reduction can be achieved with targeted therapy in the context of ongoing widespread pain. Localized pain improvement was measured by a novel questionnaire developed for this study, the modified Nordic Musculoskeletal Questionnaire (NMQ). Between-group differences in FIQ-R did not reach statistical significance, but the total change scores on FIQ-R for the MFR group (mean = 10.14, SD = 16.2) trended in the hypothesized and positive direction compared to the Swedish massage group (mean = 0.33, SD = 4.93) yielding a positive Aikin separation test. Although overall modified NMQ scores improved in both groups there were no consistent focal areas of improvement for the Swedish massage group. In contrast, the MFR group reported consistent pain reductions in the neck and upper back regions on the NMQ. These data support the need for larger randomized controlled trials of MFR versus other massage techniques and support the assessment of localized pain reduction in future manual therapy studies in FM. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of non-ST segment elevation acute chest pain syndromes with a novel low-profile continuous imaging ultrasound transducer.

PubMed

Chandraratna, P Anthony N; Mohar, Dilbahar S; Sidarous, Peter F; Brar, Prabhjyot; Miller, Jeffrey; Shah, Nissar; Kadis, John; Ali, Ashgar; Mohar, Prabhsimran

2012-09-01

This investigation was designed to test the hypothesis that continuous cardiac imaging using an ultrasound transducer developed in our laboratory (ContiScan) is superior to electrocardiogram (ECG) monitoring in the diagnosis of coronary artery disease (CAD) in patients with acute non-ST segment elevation chest pain syndromes. Seventy patients with intermediate to high probability of CAD who presented with typical anginal chest pain and no evidence of ST segment elevation on the ECG were studied. The 2.5-MHz transducer is spherical in its distal part mounted in an external housing to permit steering in 360 degrees. The transducer was placed at the left sternal border to image the left ventricular short-axis view and recorded on video tape at baseline, during and after episodes of chest pain. Two ECG leads were continuously monitored. The presence of CAD was confirmed by coronary arteriography or nuclear or echocardiographic stress testing. Twenty-four patients had regional wall motion abnormalities (RWMA) on their initial echo which were unchanged during the period of monitoring. All had evidence of CAD. Twenty-eight patients had transient RWMA. All had evidence of CAD. Eighteen patients had normal wall motion throughout the monitoring period, 14 of these had no evidence of CAD, and four had evidence of CAD. These four patients did not have chest pain during monitoring. The sensitivity, specificity, and accuracy of echocardiographic monitoring for diagnosing non-ST elevation myocardial infarction was 88%, 100%, and 91% respectively. The sensitivity, specificity, and accuracy of the ECG for diagnosis of CAD were 31%, 100%, and 52%, respectively. Echocardiography was superior to ECG (P < 0.001). The data indicate that continuous cardiac imaging is superior to ECG monitoring for the diagnosis of CAD in patients presenting with acute non-ST segment elevation chest pain syndromes. This technique could be a useful adjunct to ECG monitoring for myocardial ischemia in the acute care setting. © 2012, Wiley Periodicals, Inc.

Impact of pain on cognitive functions in primary Sjögren syndrome with small fiber neuropathy

PubMed Central

Indart, Sandrine; Hugon, Jacques; Guillausseau, Pierre Jean; Gilbert, Alice; Dumurgier, Julien; Paquet, Claire; Sène, Damien

2017-01-01

Abstract Primary Sjögren syndrome (pSS) is a chronic systemic autoimmune disease characterized by xerophthalmia, xerostomia, and potential peripheral or central neurological involvement. In pSS, the prevalence of cognitive disorders is generally sparse across literature and the impact of pain on cognitive profile is unclear. The aim of this study was to determine the relation between pain, cognitive complaint, and impairment in a very homogenous population of 10 pSS patients with painful small fiber neuropathy (PSFN) and spontaneous cognitive complaint. Neurological exam, neuropsychological assessment, clinical evaluation measuring pain level, fatigue, anxiety, depression, and cognitive complaint were performed. Our results showed that 100% of patients had cognitive dysfunction especially in executive domain (80%). The most sensitive test was the Wisconsin Card Sorting Test (WCST), abnormal in 70% of our population. Moreover, we found clear cut significant correlations between pain levels and 3 measures of WCST: the number of errors (R = –0.768, P = .0062), perseverations (R = 0.831, P = .0042), and categories (R = 0.705, P = .02). In the literature review, the impact of pain is underexplored and results could be discordant. In a homogeneous cohort of pSS patients with PSFN, a cognitive complaint seems to be a valid reflection of cognitive dysfunction marked by a specific executive profile found with the WCST. In this preliminary study, this profile is linked to the level of pain and highlights that an appropriate management of pain control and a cognitive readaptation in patients could improve the quality of life. PMID:28422829

Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice.

PubMed

Negus, S Stevens; Neddenriep, Bradley; Altarifi, Ahmad A; Carroll, F Ivy; Leitl, Michael D; Miller, Laurence L

2015-06-01

Pain-related functional impairment and behavioral depression are diagnostic indicators of pain and targets for its treatment. Nesting is an innate behavior in mice that may be sensitive to pain manipulations and responsive to analgesics. The goal of this study was to develop and validate a procedure for evaluation of pain-related depression of nesting in mice. Male ICR mice were individually housed and tested in their home cages. On test days, a 5- × 5-cm Nestlet was subdivided into 6 pieces, the pieces were evenly distributed on the cage floor, and Nestlet consolidation was quantified during 100-minute sessions. Baseline nesting was stable within and between subjects, and nesting was depressed by 2 commonly used inflammatory pain stimuli (intraperitoneal injection of dilute acid; intraplantar injection of complete Freund adjuvant). Pain-related depression of nesting was alleviated by drugs from 2 classes of clinically effective analgesics (the nonsteroidal anti-inflammatory drug ketoprofen and the μ-opioid receptor agonist morphine) but not by a drug from a class that has failed to yield effective analgesics (the centrally acting kappa opioid agonist U69,593). Neither ketoprofen nor morphine alleviated depression of nesting by U69,593, which suggests that ketoprofen and morphine effects were selective for pain-related depression of nesting. In contrast to ketoprofen and morphine, the kappa opioid receptor antagonist JDTic blocked depression of nesting by U69,593 but not by acid or complete Freund adjuvant. These results support utility of this procedure to assess expression and treatment of pain-related depression in mice.

Impact of pain on cognitive functions in primary Sjögren syndrome with small fiber neuropathy: 10 cases and a literature review.

PubMed

Indart, Sandrine; Hugon, Jacques; Guillausseau, Pierre Jean; Gilbert, Alice; Dumurgier, Julien; Paquet, Claire; Sène, Damien

2017-04-01

Primary Sjögren syndrome (pSS) is a chronic systemic autoimmune disease characterized by xerophthalmia, xerostomia, and potential peripheral or central neurological involvement. In pSS, the prevalence of cognitive disorders is generally sparse across literature and the impact of pain on cognitive profile is unclear. The aim of this study was to determine the relation between pain, cognitive complaint, and impairment in a very homogenous population of 10 pSS patients with painful small fiber neuropathy (PSFN) and spontaneous cognitive complaint. Neurological exam, neuropsychological assessment, clinical evaluation measuring pain level, fatigue, anxiety, depression, and cognitive complaint were performed. Our results showed that 100% of patients had cognitive dysfunction especially in executive domain (80%). The most sensitive test was the Wisconsin Card Sorting Test (WCST), abnormal in 70% of our population. Moreover, we found clear cut significant correlations between pain levels and 3 measures of WCST: the number of errors (R = -0.768, P = .0062), perseverations (R = 0.831, P = .0042), and categories (R = 0.705, P = .02). In the literature review, the impact of pain is underexplored and results could be discordant. In a homogeneous cohort of pSS patients with PSFN, a cognitive complaint seems to be a valid reflection of cognitive dysfunction marked by a specific executive profile found with the WCST. In this preliminary study, this profile is linked to the level of pain and highlights that an appropriate management of pain control and a cognitive readaptation in patients could improve the quality of life.

Psychosocial factors partially mediate the relationship between mechanical hyperalgesia and self-reported pain.

PubMed

Mason, Kayleigh J; O'Neill, Terence W; Lunt, Mark; Jones, Anthony K P; McBeth, John

2018-01-26

Amplification of sensory signalling within the nervous system along with psychosocial factors contributes to the variation and severity of knee pain. Quantitative sensory testing (QST) is a non-invasive test battery that assesses sensory perception of thermal, pressure, mechanical and vibration stimuli used in the assessment of pain. Psychosocial factors also have an important role in explaining the occurrence of pain. The aim was to determine whether QST measures were associated with self-reported pain, and whether those associations were mediated by psychosocial factors. Participants with knee pain identified from a population-based cohort completed a tender point count and a reduced QST battery of thermal, mechanical and pressure pain thresholds, temporal summation, mechanical pain sensitivity (MPS), dynamic mechanical allodynia (DMA) and vibration detection threshold performed following the protocol by the German Research Network on Neuropathic Pain. QST assessments were performed at the most painful knee and opposite forearm (if pain-free). Participants were asked to score for their global and knee pain intensities within the past month (range 0-10), and complete questionnaire items investigating anxiety, depression, illness perceptions, pain catastrophising, and physical functioning. QST measures (independent variable) significantly correlated (Spearman's rho) with self-reported pain intensity (dependent variable) were included in structural equation models with psychosocial factors (latent mediators). Seventy-two participants were recruited with 61 participants (36 women; median age 64 years) with complete data included in subsequent analyses. Tender point count was significantly correlated with global pain intensity. DMA at the knee and MPS at the most painful knee and opposite pain-free forearm were significantly correlated with both global pain and knee pain intensities. Psychosocial factors including pain catastrophising sub-scales (rumination and helplessness) and illness perceptions (consequences and concern) were significant partial mediators of the association with global pain intensity when loaded on to a latent mediator for: tender point count [75% total effect; 95% confidence interval (CI) 22%, 100%]; MPS at the knee (49%; 12%, 86%); and DMA at the knee (63%; 5%, 100%). Latent psychosocial factors were also significant partial mediators of the association between pain intensity at the tested knee with MPS at the knee (30%; 2%, 58%), but not for DMA at the knee. Measures of mechanical hyperalgesia at the most painful knee and pain-free opposite forearm were associated with increased knee and global pain indicative of altered central processing. Psychosocial factors were significant partial mediators, highlighting the importance of the central integration of emotional processing in pain perception. Associations between mechanical hyperalgesia at the forearm and knee, psychosocial factors and increased levels of clinical global and knee pain intensity provide evidence of altered central processing as a key mechanism in knee pain, with psychological factors playing a key role in the expression of clinical pain.

Somatic syndromes and chronic pain in women with overactive bladder

PubMed Central

Reynolds, W. Stuart; Mock, Stephen; Zhang, Xuechao; Kaufman, Melissa; Wein, Alan; Bruehl, Stephen; Dmochowski, Roger

2016-01-01

Aims Mechanisms underlying pain perception and afferent hypersensitivity, such as central sensitization, may impact overactive bladder (OAB) symptoms. However, little is known about associations between OAB symptom severity, pain experience, and presence of comorbid chronic pain syndromes. This study examined relationships between OAB symptoms, somatic symptoms, and specific chronic pain conditions in which central sensitization is believed to play a primary role, in a community-based sample of adult women with OAB Methods We recruited adult women with OAB to complete questionnaires assessing urinary symptoms, pain and somatic symptoms, and preexisting diagnoses of central sensitivity syndromes. We analyzed the effects of overall bodily pain intensity, general somatic symptoms, and diagnoses of central sensitivity syndromes on OAB symptom bother and health-related quality of life. Results Of the 116 women in this study, over half (54%) stated their urge to urinate was associated with pain, pressure, or discomfort. Participants reported a wide range of OAB symptoms and health-related quality of life. There was a significant, positive correlation between OAB symptoms and somatic symptoms as well as overall pain intensity. Only 7% of women met diagnostic criteria for fibromyalgia; yet these women demonstrated significantly increased OAB symptom burden and decreased OAB quality of life compared to those without fibromyalgia. Conclusion Women with more severe OAB symptoms reported increased general somatic symptom burden and increased overall body pain intensity, especially women with fibromyalgia. These findings suggest that attributes of pain and co-morbidity with chronic pain conditions may impact the experience of OAB symptoms for many women. PMID:27367486

The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia

PubMed Central

2011-01-01

Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids). PMID:21542893

Differential Efficacy of Ketamine in the Acute versus Chronic Stages of Complex Regional Pain Syndrome in Mice

PubMed Central

Tajerian, Maral; Leu, David; Yang, Phillip; Huang, Ting Ting; Kingery, Wade S; Clark, J David

2015-01-01

Background Complex regional pain syndrome (CRPS) is a painful, disabling and often chronic condition, where many patients transition from an acute phase with prominent peripheral neurogenic inflammation to a chronic phase with evident central nervous system (CNS) changes. Ketamine is a centrally-acting agent believed to work through blockade of N-methyl-D-aspartate (NMDA) receptors and is being increasingly used for the treatment of refractory CRPS, although the basis for the drug’s effects and efficacy at different stages of the syndrome remain unclear. Methods We used a mouse model of CRPS (n=8–12/group) involving tibia fracture/cast immobilization to test the efficacy of ketamine (2 mg/kg/day; 7 days) or vehicle infusion during acute (3weeks [3w] post-fracture) and chronic (7w post-fracture) stages. Results Acute phase fracture mice displayed elevated limb temperature, edema and nociceptive sensitization that were not reduced by ketamine. Fracture mice treated with ketamine during the chronic phase showed reduced nociceptive sensitization that persisted beyond completion of the infusion. During this chronic phase, ketamine also reduced latent nociceptive sensitization and improved motor function at 18 weeks post-fracture. No side effects of the infusions were identified. These behavioral changes were associated with altered spinal astrocyte activation and expression of pain-related proteins including NMDA receptor 2b (NR2b), Ca2+/calmodulin-dependent protein kinase ii (CaMK2), and brain-derived neurotrophic factor (BNDF). Conclusions Collectively, these results demonstrate that ketamine is efficacious in the chronic, but not acute stages of CRPS, suggesting that the centrally-acting drug is relatively ineffective in early CRPS when peripheral mechanisms are more critical for supporting nociceptive sensitization. PMID:26492479

Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain.

PubMed

Drinovac Vlah, V; Bach-Rojecky, L; Lacković, Z

2016-12-01

"Mirror pain" or mirror-image pain (MP) is pain opposite to the side of injury. Mechanism and frequency in humans are not known. There is no consent on therapy. Here we report that unilaterally injected botulinum toxin type A (BT-A) has bilateral effect in experimental MP, thus deserves to be investigated as therapy for this condition. We examined the localization of BT-A's bilateral antinociceptive action in MP induced by 3 % carrageenan intramuscular injection in Wistar rats. BT-A was applied peripherally (5 U/kg), into ipsilateral or contralateral hind paw pad (i.pl.) and centrally (1 U/kg), at spinal (intrathecally, i.t.) or supraspinal (intracisternally, i.c.) level. Additionally, we examined the involvement of central opioid and GABAergic systems, as well as the contribution of peripheral capsaicin-sensitive neurons to BT-A's bilateral antinociceptive effect. Ipsilateral i.pl. and i.t. BT-A reduced the bilateral mechanical sensitivity to von Frey filaments, while contralateral i.pl. and i.c. treatments had no effect on either tested side. Bilateral antinociceptive effect of ipsilateral i.pl. BT-A was prevented by μ-opioid antagonist naloxonazine (1.5 μg/10 μl) and GABA A antagonist bicuculline (1 μg/10 μl) if applied at the spinal level, in contrast to supraspinal application of the same doses. Local treatment of sciatic nerve with 2 % capsaicin 5 days following BT-A i.pl. injection caused desensitization of sciatic capsaicin-sensitive fibers, but did not affect bilateral antinociceptive effect of BT-A and the presence of cleaved SNAP-25 at the spinal cord slices. Present experiments suggest segmental actions of peripheral BT-A at spinal level, which are probably not solely dependent on capsaicin-sensitive neurons.

Association of Leptin with Body Pain in Women

PubMed Central

Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D.; Stefanick, Marcia L.

2016-01-01

Abstract Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia. PMID:27028709

Association of Leptin with Body Pain in Women.

PubMed

Younger, Jarred; Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D; Stefanick, Marcia L

2016-07-01

Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity.

PubMed

Baad-Hansen, L; Cairns, Be; Ernberg, M; Svensson, P

2010-01-01

We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.

ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1981-01-01

The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

Transient anorexia, hyper-nociception and cognitive impairment in early adjuvant arthritis in rats.

PubMed

Skurlova, M; Stofkova, A; Kiss, A; Belacek, J; Pecha, O; Deykun, K; Jurcovicova, J

2010-10-01

Rheumatoid arthritis (RA) is associated with enhanced pro-inflammatory cytokine levels, pain, anorexia, and cognitive changes. The enhanced production of cytokines appears before the full manifestation of the disease. So far, any experimental data on behavioral effects of early arthritis are lacking. In the present series we describe anorexia early changes in, pain hyper-sensitivity and altered cognitive behavior during the first four days of adjuvant arthritis in rats (AA), when no clinical signs are yet apparent. AA was induced to male Lewis rats by a single injection of complete Freund's adjuvant (cFA) at the base of the tail. Plasma leptin and ghrelin were measured using specific RIA methods. Gene expressions for food-regulatory peptides, neuropeptide-Y (NPY) and interleukin-1β (IL-1β) in the hypothalamic arcuate nuclei (nARC), were quantitated by TaqMan real-time PCR. Pain sensation was measured on all four limbs and tail by the plantar test. Cognitive functions were tested in the Morris water maze (MWM). Levels of orexigenic ghrelin as well as mRNA expression of orexigenic NPY in nucleus arcuatus (nRC)re significantly enhanced on day 2 of AA only. Reduced body weight and food intake persisted by day 4 with the most profound reduction on day 2. The mRNA for anorexigenic IL-1β in the nARC was significantly enhanced on days 2 and 4. Enhanced pain sensitivity was observed on day 2, as was the cognitive impairment given by longer time to find the hidden platform, longer time spent in thigmotaxis zone, and longer trajectory. The less effective strategy used to find the hidden platform was observed up to the day 4 of AA. Early stage of AA brings about reduced body weight, food intake, and activation of central orexigenic pathways. The observed anorexia could be ascribed to the over-expression of anorexigenic IL-1β which dominates over the NPY orexigenic effects. On day 2 of AA higher pain sensitivity and cognitive impairment appear. All the observed change tend to recover by day 4 of the disease.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

PubMed

Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-07-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Inter- and intra-observer reliability of clinical movement-control tests for marines

PubMed Central

2012-01-01

Background Musculoskeletal disorders particularly in the back and lower extremities are common among marines. Here, movement-control tests are considered clinically useful for screening and follow-up evaluation. However, few studies have addressed the reliability of clinical tests, and no such published data exists for marines. The present aim was therefore to determine the inter- and intra-observer reliability of clinically convenient tests emphasizing movement control of the back and hip among marines. A secondary aim was to investigate the sensitivity and specificity of these clinical tests for discriminating musculoskeletal pain disorders in this group of military personnel. Methods This inter- and intra-observer reliability study used a test-retest approach with six standardized clinical tests focusing on movement control for back and hip. Thirty-three marines (age 28.7 yrs, SD 5.9) on active duty volunteered and were recruited. They followed an in-vivo observation test procedure that covered both low- and high-load (threshold) tasks relevant for marines on operational duty. Two independent observers simultaneously rated performance as “correct” or “incorrect” following a standardized assessment protocol. Re-testing followed 7–10 days thereafter. Reliability was analysed using kappa (κ) coefficients, while discriminative power of the best-fitting tests for back- and lower-extremity pain was assessed using a multiple-variable regression model. Results Inter-observer reliability for the six tests was moderate to almost perfect with κ-coefficients ranging between 0.56-0.95. Three tests reached almost perfect inter-observer reliability with mean κ-coefficients > 0.81. However, intra-observer reliability was fair-to-moderate with mean κ-coefficients between 0.22-0.58. Three tests achieved moderate intra-observer reliability with κ-coefficients > 0.41. Combinations of one low- and one high-threshold test best discriminated prior back pain, but results were inconsistent for lower-extremity pain. Conclusions Our results suggest that clinical tests of movement control of back and hip are reliable for use in screening protocols using several observers with marines. However, test-retest reproducibility was less accurate, which should be considered in follow-up evaluations. The results also indicate that combinations of low- and high-threshold tests have discriminative validity for prior back pain, but were inconclusive for lower-extremity pain. PMID:23273285

ACR Appropriateness Criteria® acute onset flank pain--suspicion of stone disease.

PubMed

Coursey, Courtney A; Casalino, David D; Remer, Erick M; Arellano, Ronald S; Bishoff, Jay T; Dighe, Manjiri; Fulgham, Pat; Goldfarb, Stanley; Israel, Gary M; Lazarus, Elizabeth; Leyendecker, John R; Majd, Massoud; Nikolaidis, Paul; Papanicolaou, Nicholas; Prasad, Srinivasa; Ramchandani, Parvati; Sheth, Sheila; Vikram, Raghunandan

2012-09-01

Low dose (<3 mSv) noncontrast CT (NCCT) is the imaging study of choice for accurate evaluation of patients with acute onset of flank pain and suspicion of stone disease (sensitivity 97%, specificity 95%). NCCT can reliably characterize the location and size of an offending ureteral calculus, identify complications, and diagnose alternative etiologies of abdominal pain such as appendicitis. By comparison, the sensitivity of radiographs (59%) and ultrasound (24-57%) for the detection of renal and ureteral calculi is relatively poor. Ultrasound can accurately diagnose pelvicaliectasis and ureterectasis, but it may take several hours for these findings to develop. In the pregnant patient, however, ultrasound is a first line test as it does not expose the fetus to ionizing radiation. MR is an accurate test for the diagnosis of pelvicaliectasis and ureterectasis, but is less sensitive than CT for the diagnosis of renal and ureteral calculi. For patients with known stone disease whose stones are visible on radiographs, radiographs are a good tool for post-treatment follow-up.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Post-operative orofacial pain, temporomandibular dysfunction and trigeminal sensitivity after recent pterional craniotomy: preliminary study.

PubMed

Brazoloto, Thiago Medina; de Siqueira, Silvia Regina Dowgan Tesseroli; Rocha-Filho, Pedro Augusto Sampaio; Figueiredo, Eberval Gadelha; Teixeira, Manoel Jacobsen; de Siqueira, José Tadeu Tesseroli

2017-05-01

Surgical trauma at the temporalis muscle is a potential cause of post-craniotomy headache and temporomandibular disorders (TMD). The aim of this study was to evaluate the prevalence of pain, masticatory dysfunction and trigeminal somatosensory abnormalities in patients who acquired aneurysms following pterional craniotomy. Fifteen patients were evaluated before and after the surgical procedure by a trained dentist. The evaluation consisted of the (1) research diagnostic criteria for TMD, (2) a standardized orofacial pain questionnaire and (3) a systematic protocol for quantitative sensory testing (QST) for the trigeminal nerve. After pterional craniotomy, 80% of the subjects, 12 patients, developed orofacial pain triggered by mandibular function. The pain intensity was measured by using the visual analog scale (VAS), and the mean pain intensity was 3.7. The prevalence of masticatory dysfunction was 86.7%, and there was a significant reduction of the maximum mouth opening. The sensory evaluation showed tactile and thermal hypoesthesia in the area of pterional access in all patients. There was a high frequency of temporomandibular dysfunction, postoperative orofacial pain and trigeminal sensory abnormalities. These findings can help to understand several abnormalities that can contribute to postoperative headache or orofacial pain complaints after pterional surgeries.

Predicting acute pain after cesarean delivery using three simple questions.

PubMed

Pan, Peter H; Tonidandel, Ashley M; Aschenbrenner, Carol A; Houle, Timothy T; Harris, Lynne C; Eisenach, James C

2013-05-01

Interindividual variability in postoperative pain presents a clinical challenge. Preoperative quantitative sensory testing is useful but time consuming in predicting postoperative pain intensity. The current study was conducted to develop and validate a predictive model of acute postcesarean pain using a simple three-item preoperative questionnaire. A total of 200 women scheduled for elective cesarean delivery under subarachnoid anesthesia were enrolled (192 subjects analyzed). Patients were asked to rate the intensity of loudness of audio tones, their level of anxiety and anticipated pain, and analgesic need from surgery. Postoperatively, patients reported the intensity of evoked pain. Regression analysis was performed to generate a predictive model for pain from these measures. A validation cohort of 151 women was enrolled to test the reliability of the model (131 subjects analyzed). Responses from each of the three preoperative questions correlated moderately with 24-h evoked pain intensity (r = 0.24-0.33, P < 0.001). Audio tone rating added uniquely, but minimally, to the model and was not included in the predictive model. The multiple regression analysis yielded a statistically significant model (R = 0.20, P < 0.001), whereas the validation cohort showed reliably a very similar regression line (R = 0.18). In predicting the upper 20th percentile of evoked pain scores, the optimal cut point was 46.9 (z =0.24) such that sensitivity of 0.68 and specificity of 0.67 were as balanced as possible. This simple three-item questionnaire is useful to help predict postcesarean evoked pain intensity, and could be applied to further research and clinical application to tailor analgesic therapy to those who need it most.

Asymmetric dimethylarginine may mediate increased heat pain threshold in experimental chronic kidney disease.

PubMed

Kielstein, Jan T; Suntharalingam, Mayuren; Perthel, Ronny; Rong, Song; Martens-Lobenhoffer, Jens; Jäger, Kristin; Bode-Böger, Stefanie M; Nave, Heike

2012-03-01

Thermal sensitivity in uraemia is decreased. Non-selective synthetic nitric oxide synthase (NOS) inhibitors significantly attenuate thermal hyperalgesia in preclinical models. The aim of our study was to evaluate the effect of experimental uraemia, which is associated with an increase of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), on thermal sensitivity in rats. Furthermore, we intended to study the effect of chronic ADMA infusion alone on thermal sensitivity. Male Sprague-Dawley rats (n = 54), 10 weeks old, weight 370-430 g, were randomly assigned to three groups receiving either (i) isotonic saline or (ii) ADMA via osmotic mini pumps or (iii) underwent 5/6 nephrectomy (Nx). After 14 days, 50% of all animals from all groups underwent thermal sensitivity testing and terminal blood draw. After 28 days, the remaining animals underwent the same procedures. Thermal sensitivity examination was performed by the hot-plate test, measuring time from heat exposition to first paw licking or jumping of the animal. While the median [interquartile range] latency time between heat exposition to first paw licking or jumping of the animal in the NaCl infusion group remained unchanged between Day 14 (8.4 [6.75-11.50] s) and Day 28 (7.35 [6.10-7.90] s) both, ADMA infusion and 5/6 nephrectomy tended to increase the thermal pain threshold at Day 14 (9.25 [6.55-12.18] s) and (9.50 [5.8 ± 11.0] s), respectively, compared to NaCl on Day 14 (8.4 [6.75-11.50] s). This difference became statistical significant at Day 28 where the median latency time in the ADMA group (13.10 [11.85-15.95] s) and in the 5/6 Nx group (13.50 [10.85-17.55] s) were significantly higher than in the NaCl group (7.35 [6.10-7.90] s). Induction of progressive renal failure in rats by 5/6 nephrectomy, which is accompanied by a marked increase of the serum levels of the endogenous NOS inhibitor ADMA, leads to a significantly increased heat pain threshold at 28 days. The sole infusion of ADMA into healthy rats leads to the same increase in heat pain threshold.

An increased response to experimental muscle pain is related to psychological status in women with chronic non-traumatic neck-shoulder pain

PubMed Central

2011-01-01

Background Neck-shoulder pain conditions, e.g., chronic trapezius myalgia, have been associated with sensory disturbances such as increased sensitivity to experimentally induced pain. This study investigated pain sensitivity in terms of bilateral pressure pain thresholds over the trapezius and tibialis anterior muscles and pain responses after a unilateral hypertonic saline infusion into the right legs tibialis anterior muscle and related those parameters to intensity and area size of the clinical pain and to psychological factors (sleeping problems, depression, anxiety, catastrophizing and fear-avoidance). Methods Nineteen women with chronic non-traumatic neck-shoulder pain but without simultaneous anatomically widespread clinical pain (NSP) and 30 age-matched pain-free female control subjects (CON) participated in the study. Results NSP had lower pressure pain thresholds over the trapezius and over the tibialis anterior muscles and experienced hypertonic saline-evoked pain in the tibialis anterior muscle to be significantly more intense and locally more widespread than CON. More intense symptoms of anxiety and depression together with a higher disability level were associated with increased pain responses to experimental pain induction and a larger area size of the clinical neck-shoulder pain at its worst. Conclusion These results indicate that central mechanisms e.g., central sensitization and altered descending control, are involved in chronic neck-shoulder pain since sensory hypersensitivity was found in areas distant to the site of clinical pain. Psychological status was found to interact with the perception, intensity, duration and distribution of induced pain (hypertonic saline) together with the spreading of clinical pain. The duration and intensity of pain correlated negatively with pressure pain thresholds. PMID:21992460

Allodynia and Dysmenorrhea.

PubMed

Jarrell, John; Arendt-Nielsen, Lars

2016-03-01

Cutaneous allodynia (pain from a non-painful stimulus) is a sign that can be observed among women with chronic pelvic pain. Dysmenorrhea is recognized as a common cause of chronic pelvic pain in women. This study was conducted to explore the frequency of allodynia and the relationship between allodynia and severe dysmenorrhea. We enrolled women in this study if they had experienced chronic pelvic pain for more than six months. Women provided information regarding their chronic pelvic pain and menstrual function, specifically the severity of their menstrual pain. In addition to a gynaecological assessment, women were tested for allodynia and pain pressure thresholds. Abdominal allodynia was present in 62.1% of 181 women who participated. Women with allodynia had a significantly greater rate of severe dysmenorrhea and significantly greater duration of severe dysmenorrhea. Pain pressure thresholds were demonstrated to decrease significantly in relation to increasing duration of severe dysmenorrhea. There is a greater frequency of chronic pain among women with a history of severe dysmenorrhea. Women who experienced prolonged severe dysmenorrhea were shown to have a progressive increase in pain sensitivity (reflected in reduced pain pressure thresholds). These findings support efforts to manage dysmenorrhea early in a woman's life with approaches to suppress menstrual function. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

Immediate effects of spinal manipulation on thermal pain sensitivity: an experimental study

PubMed Central

George, Steven Z; Bishop, Mark D; Bialosky, Joel E; Zeppieri, Giorgio; Robinson, Michael E

2006-01-01

Background The underlying causes of spinal manipulation hypoalgesia are largely unknown. The beneficial clinical effects were originally theorized to be due to biomechanical changes, but recent research has suggested spinal manipulation may have a direct neurophysiological effect on pain perception through dorsal horn inhibition. This study added to this literature by investigating whether spinal manipulation hypoalgesia was: a) local to anatomical areas innervated by the lumbar spine; b) correlated with psychological variables; c) greater than hypoalgesia from physical activity; and d) different for A-delta and C-fiber mediated pain perception. Methods Asymptomatic subjects (n = 60) completed baseline psychological questionnaires and underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception. Subjects were then randomized to ride a stationary bicycle, perform lumbar extension exercise, or receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes after the intervention period. Data were analyzed with repeated measures ANOVA and post-hoc testing was performed with Bonferroni correction, as appropriate. Results Subjects in the three intervention groups did not differ on baseline characteristics. Hypoalgesia from spinal manipulation was observed in lumbar innervated areas, but not control (cervical innervated) areas. Hypoalgesic response was not strongly correlated with psychological variables. Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ from stationary bicycle and lumbar extension (p > 0.05). Spinal manipulation hypoalgesia for C-fiber mediated pain perception was greater than stationary bicycle riding (p = 0.040), but not for lumbar extension (p = 0.105). Conclusion Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic mechanism of spinal manipulation for asymptomatic subjects, but further study is required to replicate this finding in subjects with low back pain. PMID:16911795

Electroencephalographic activity in response to procedural pain in preterm infants born at 28 and 33 weeks gestational age.

PubMed

Maimon, Neta; Grunau, Ruth E; Cepeda, Ivan L; Friger, Michael; Selnovik, Leonel; Gilat, Shlomo; Shany, Eilon

2013-12-01

Preterm infants undergo frequent painful procedures in the neonatal intensive care unit. Electroencephalography (EEG) changes in reaction to invasive procedures have been reported in preterm and full-term neonates. Frontal EEG asymmetry as an index of emotion during tactile stimulation shows inconsistent findings in full-term infants, and has not been examined in the context of pain in preterm infants. Our aim was to examine whether heel lance for blood collection induces changes in right-left frontal asymmetry, suggesting negative emotional response, in preterm neonates at different gestational age (GA) at birth and different duration of stay in the neonatal intensive care unit. Three groups of preterm infants were compared: set 1: group 1 (n=24), born and tested at 28 weeks GA; group 2 (n=22), born at 28 weeks GA and tested at 33 weeks; set 2: group 3 (n=25), born and tested at 33 weeks GA. EEG power was calculated for 30-second artifact-free periods, in standard frequency bandwidths, in 3 phases (baseline, up to 5 min after heel lance, 10 min after heel lance). No significant differences were found in right-left frontal asymmetry, or in ipsilateral or contralateral somatosensory response, across phases. In contrast, the Behavioral Indicators of Infant Pain scores changed across phase (P<0.0001). Infants in group 1 showed lower Behavioral Indicators of Infant Pain scores (P=0.039). There are technical challenges in recording EEG during procedures, as pain induces motor movements. More research is needed to determine the most sensitive approach to measure EEG signals within the context of pain in infancy.

Computerized Cuff Pressure Algometry as Guidance for Circumferential Tissue Compression for Wearable Soft Robotic Applications: A Systematic Review.

PubMed

Kermavnar, Tjaša; Power, Valerie; de Eyto, Adam; O'Sullivan, Leonard W

2018-02-01

In this article, we review the literature on quantitative sensory testing of deep somatic pain by means of computerized cuff pressure algometry (CPA) in search of pressure-related safety guidelines for wearable soft exoskeleton and robotics design. Most pressure-related safety thresholds to date are based on interface pressures and skin perfusion, although clinical research suggests the deep somatic tissues to be the most sensitive to excessive loading. With CPA, pain is induced in deeper layers of soft tissue at the limbs. The results indicate that circumferential compression leads to discomfort at ∼16-34 kPa, becomes painful at ∼20-27 kPa, and can become unbearable even below 40 kPa.

The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

PubMed

Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

2015-08-01

Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

A clinical perspective on a pain neuroscience education approach to manual therapy.

PubMed

Louw, Adriaan; Nijs, Jo; Puentedura, Emilio J

2017-07-01

In recent years, there has been an increased interest in pain neuroscience education (PNE) in physical therapy. There is growing evidence for the efficacy of PNE to decrease pain, disability, fear-avoidance, pain catastrophization, limited movement, and health care utilization in people struggling with pain. PNE teaches people in pain more about the biology and physiology of their pain experience including processes such as central sensitization, peripheral sensitization, allodynia, inhibition, facilitation, neuroplasticity and more. PNE's neurobiological model often finds itself at odds with traditional biomedical models used in physical therapy. Traditional biomedical models, focusing on anatomy, pathoanatomy, and biomechanics have been shown to have limited efficacy in helping people understand their pain, especially chronic pain, and may in fact even increase a person's pain experience by increasing fear-avoidance and pain catastrophization. An area of physical therapy where the biomedical model is used a lot is manual therapy. This contrast between PNE and manual therapy has seemingly polarized followers from each approach to see PNE as a 'hands-off' approach even having clinicians categorize patients as either in need of receiving PNE (with no hands-on), or hands-on with no PNE. In this paper, we explore the notion of PNE and manual therapy co-existing. PNE research has shown to have immediate effects of various clinical signs and symptoms associated with central sensitization. Using a model of sensitization (innocuous, noxious, and allodynia), we argue that PNE can be used in a manual therapy model, especially treating someone where the nervous system has become increasingly hypervigilant. Level of Evidence : VII.

Metal Hypersensitivity and Total Knee Arthroplasty

PubMed Central

Lachiewicz, Paul F.; Watters, Tyler Steven; Jacobs, Joshua J.

2015-01-01

Metal hypersensitivity in patients with a total knee arthroplasty (TKA) is a controversial topic. The diagnosis is difficult, given the lack of robust clinical validation of the utility of cutaneous and in vitro testing. Metal hypersensitivity after TKA is quite rare and should be considered after eliminating other causes of pain and swelling, such as low-grade infection, instability, component loosening or malrotation, referred pain, and chronic regional pain syndrome. Anecdotal observations suggest that two clinical presentations of metal hypersensitivity may occur after TKA: dermatitis or a persistent painful synovitis of the knee. Patients may or may not have a history of intolerance to metal jewelry. Laboratory studies, including erythrocyte sedimentation rate, C-reactive protein level, and knee joint aspiration, are usually negative. Cutaneous and in vitro testing have been reported to be positive, but the sensitivity and specificity of such testing has not been defined. Anecdotal reports suggest that, if metal hypersensitivity is suspected and nonsurgical measures have failed, then revision to components fabricated of titanium alloy or zirconium coating can be successful in relieving symptoms. Revision should be considered as a last resort, however, and patients should be informed that no evidence-based medicine is available to guide the management of these conditions, particularly for decisions regarding revision. Given the limitations of current testing methods, the widespread screening of patients for metal allergies before TKA is not warranted. PMID:26752739

Relationship of Corneal Pain Sensitivity With Dry Eye Symptoms in Dry Eye With Short Tear Break-Up Time.

PubMed

Kaido, Minako; Kawashima, Motoko; Ishida, Reiko; Tsubota, Kazuo

2016-03-01

The purpose of this prospective comparative study was to investigate corneal sensitivity in subjects with unstable tear film, with and without dry eye (DE) symptoms. Forty-one eyes of 41 volunteers (mean age: 45.1 ± 9.4 years; age range, 23-57 years), with normal tear function and ocular surface except for tear stability, were studied. The eyes were divided into two groups depending on the presence or absence of DE symptoms: 21 eyes with DE symptoms (symptomatic group); and 20 eyes without DE symptoms (asymptomatic group). Three types of corneal sensitivity values were measured using a Cochet-Bonnet esthesiometer: the sensitivity for perception of touch (S-touch), the sensitivity for blinking (S-blink), and the sensitivity for pain (S-pain). Mean S-blink and S-pain were significantly higher in the symptomatic group than in the asymptomatic group (P < 0.05), whereas there was no significant difference in mean S-touch between these groups (P > 0.05). Corneal sensitivity for blinking and pain evoked by increased stimuli was higher in the symptomatic group (subjects with short break-up time DE) compared with subjects who have no DE symptoms despite decreased tear stability. The presence of both tear instability and hyperesthesia, rather than tear instability alone, may contribute to DE pathogenesis.

Antinociceptive effect and interaction of uncompetitive and competitive NMDA receptor antagonists upon capsaicin and paw pressure testing in normal and monoarthritic rats.

PubMed

Pelissier, Teresa; Infante, Claudio; Constandil, Luis; Espinosa, Jeannette; Lapeyra, Carolina De; Hernández, Alejandro

2008-01-01

We assessed whether intrathecal administration of the uncompetitive and competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could produce differential modulation on chemical and mechanical nociception in normal and monoarthritic rats. In addition, the antinociceptive interaction of ketamine and (+/-)CPP on monoarthritic pain was also studied using isobolographic analysis. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. Four weeks later, the antinociceptive effect of intrathecal administration of the drugs alone or combined was evaluated by using the intraplantar capsaicin and the paw pressure tests. Ketamine (0.1, 1, 10, 30, 100, 300 and 1000 microg i.t.) and (+/-)CPP (0.125, 2.5, 7.5, 12.5, 25 and 50 microg i.t.) produced significantly greater dose-dependent antinociception in the capsaicin than in the paw pressure test. Irrespective of the nociceptive test employed, both antagonists showed greater antinociceptive activity in monoarthritic than in healthy rats. Combinations produced synergy of a supra-additive nature in the capsaicin test, but only additive antinociception in paw pressure testing. The efficacy of the drugs, alone or combined, is likely to depend on the differential sensitivity of tonic versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.

Chronic pain self-management support with pain science education and exercise (COMMENCE): study protocol for a randomized controlled trial.

PubMed

Miller, Jordan; MacDermid, Joy C; Walton, David M; Richardson, Julie

2015-10-14

Previous research suggests that self-management programs for people with chronic pain improve knowledge and self-efficacy but result in negligible effects on function. This study will investigate the effectiveness self-management support with pain science education and exercise on improving function for people with chronic pain in comparison to a wait-list control. A secondary objective is to determine which variables help to predict response to the intervention. This study will be an unblinded, randomized controlled trial with 110 participants comparing a 6-week program that includes self-management support, pain science education and exercise to a wait-list control. The primary outcome will be function measured by the Short Musculoskeletal Function Assessment - Dysfunction Index. Secondary outcomes will include pain intensity measured by a numeric pain rating scale, pain interference measured by the eight-item PROMIS pain interference item-bank, how much patients are bothered by functional problems measured by the Short Musculoskeletal Function Assessment - Bother Index, catastrophic thinking measured by the Pain Catastrophizing Scale, fear of movement/re-injury measured by the 11-item Tampa Scale of Kinesiophobia, sense of perceived injustice measured by the Injustice Experience Questionnaire, self-efficacy measured by the Pain Self-Efficacy Questionnaire, pain sensitivity measured by pressure pain threshold and cold sensitivity testing, fatigue measured by a numeric fatigue rating scale, pain neurophysiology knowledge measured by the Neurophysiology of Pain Questionnaire, healthcare utilization measured by number of visits to a healthcare provider, and work status. Assessments will be completed at baseline, 7 and 18 weeks. After the 18-week assessment, the groups will crossover; however, we anticipate carry-over effects with the treatment. Therefore, data from after the crossover will be used to estimate within-group changes and to determine predictors of response that are not for direct between-group comparisons. Mixed effects modelling will be used to determine between-group differences for all primary and secondary outcomes. A series of multiple regression models will be used to determine predictors of treatment response. This study has the potential to inform future self-management programming through evaluation of a self-management program that aims to improve function as the primary outcome. ClinicalTrials.gov NCT02422459 , registered on 13 April 2015.

Assessment of nerve involvement in the lumbar spine: agreement between magnetic resonance imaging, physical examination and pain drawing findings

PubMed Central

2010-01-01

Background Detection of nerve involvement originating in the spine is a primary concern in the assessment of spine symptoms. Magnetic resonance imaging (MRI) has become the diagnostic method of choice for this detection. However, the agreement between MRI and other diagnostic methods for detecting nerve involvement has not been fully evaluated. The aim of this diagnostic study was to evaluate the agreement between nerve involvement visible in MRI and findings of nerve involvement detected in a structured physical examination and a simplified pain drawing. Methods Sixty-one consecutive patients referred for MRI of the lumbar spine were - without knowledge of MRI findings - assessed for nerve involvement with a simplified pain drawing and a structured physical examination. Agreement between findings was calculated as overall agreement, the p value for McNemar's exact test, specificity, sensitivity, and positive and negative predictive values. Results MRI-visible nerve involvement was significantly less common than, and showed weak agreement with, physical examination and pain drawing findings of nerve involvement in corresponding body segments. In spine segment L4-5, where most findings of nerve involvement were detected, the mean sensitivity of MRI-visible nerve involvement to a positive neurological test in the physical examination ranged from 16-37%. The mean specificity of MRI-visible nerve involvement in the same segment ranged from 61-77%. Positive and negative predictive values of MRI-visible nerve involvement in segment L4-5 ranged from 22-78% and 28-56% respectively. Conclusion In patients with long-standing nerve root symptoms referred for lumbar MRI, MRI-visible nerve involvement significantly underestimates the presence of nerve involvement detected by a physical examination and a pain drawing. A structured physical examination and a simplified pain drawing may reveal that many patients with "MRI-invisible" lumbar symptoms need treatment aimed at nerve involvement. Factors other than present MRI-visible nerve involvement may be responsible for findings of nerve involvement in the physical examination and the pain drawing. PMID:20831785

Short-term changes in neck pain, widespread pressure pain sensitivity, and cervical range of motion after the application of trigger point dry needling in patients with acute mechanical neck pain: a randomized clinical trial.

PubMed

Mejuto-Vázquez, María J; Salom-Moreno, Jaime; Ortega-Santiago, Ricardo; Truyols-Domínguez, Sebastián; Fernández-de-Las-Peñas, César

2014-04-01

Randomized clinical trial. To determine the effects of trigger point dry needling (TrPDN) on neck pain, widespread pressure pain sensitivity, and cervical range of motion in patients with acute mechanical neck pain and active trigger points in the upper trapezius muscle. TrPDN seems to be effective for decreasing pain in individuals with upper-quadrant pain syndromes. Potential effects of TrPDN for decreasing pain and sensitization in individuals with acute mechanical neck pain are needed. Methods Seventeen patients (53% female) were randomly assigned to 1 of 2 groups: a single session of TrPDN or no intervention (waiting list). Pressure pain thresholds over the C5-6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle; neck pain intensity; and cervical spine range-of-motion data were collected at baseline (pretreatment) and 10 minutes and 1 week after the intervention by an assessor blinded to the treatment allocation of the patient. Mixed-model analyses of variance were used to examine the effects of treatment on each outcome variable. Patients treated with 1 session of TrPDN experienced greater decreases in neck pain, greater increases in pressure pain threshold, and higher increases in cervical range of motion than those who did not receive an intervention at both 10 minutes and 1 week after the intervention (P<.01 for all comparisons). Between-group effect sizes were medium to large immediately after the TrPDN session (standardized mean score differences greater than 0.56) and large at the 1-week follow-up (standardized mean score differences greater than 1.34). The results of the current randomized clinical trial suggest that a single session of TrPDN may decrease neck pain intensity and widespread pressure pain sensitivity, and also increase active cervical range of motion, in patients with acute mechanical neck pain. Changes in pain, pressure pain threshold, and cervical range of motion surpassed their respective minimal detectable change values, supporting clinically relevant treatment effects. Level of Evidence Therapy, level 1b-.

Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.

PubMed

Singh, Jasvinder A; Noorbaloochi, Siamak; Knutson, Keith L

2017-01-14

There are few studies with an assessment of the levels of cytokines or neuropeptides as correlates of pain and pain relief in patients with painful joint diseases. Our objective was to assess whether improvements from baseline to 2-months in serum cytokine, chemokine and substance P levels were associated with clinically meaningful pain relief at 2-months post-injection in patients with painful total knee arthroplasty (TKA). Using data from randomized trial of 60 TKAs, we assessed the association of change in cytokine/chemokine/Substance P levels with primary study outcome, clinically important improvement in Western Ontario McMaster Osteoarthritis Index (WOMAC) pain subscale at 2-months post-injection using Student's t-tests and Spearman's correlation coefficient (non-parametric). Patients were categorized as pain responders (20-point reduction or more on 0-100 WOMAC pain) vs. pain non-responders. Sensitivity analysis used 0-10 daytime pain numeric rating scale (NRS) instead of WOMAC pain subscale. In a pilot study, compared to non-responders (n = 23) on WOMAC pain scale at 2-months, pain responders (n = 12) had significantly greater increase in serum levels of IL-7, IL-10, IL-12, eotaxin, interferon gamma and TNF-α from baseline to 2-months post-injection (p < 0.05 for all). Change in several cytokine/chemokine and substance P levels from pre-injection to 2-month follow-up correlated significantly with change in WOMAC pain with correlation coefficients ranging -0.37 to -0.51: IL-2, IL-7, IL-8, IL-9, IL-16, IL-12p, GCSF, IFN gamma, IP-10, MCP, MIP1b, TNF-α and VEGF (n = 35). Sensitivity analysis showed that substance P decreased significantly more from baseline to 2-months in the pain responders (0.54 ± 0.53; n = 10) than in the pain non-responders (0.48 ± 1.18; n = 9; p = 0.023) and that this change in serum substance P correlated significantly with change in daytime NRS pain, correlation coefficient was 0.53 (p = 0.021; n = 19). Findings should be interpreted with caution, since cytokine analyses were performed for a sub-group of the entire trial population. Serum cytokine, chemokine and Substance P levels correlated with pain response in patients with painful TKA after an intra-articular injection in a randomized trial.

The transitional vertebra and sacroiliac joint dysfunction association.

PubMed

Illeez, Ozge Gulsum; Atıcı, Arzu; Ulger, Esra Bahadır; Kulcu, Duygu Geler; Ozkan, Feyza Unlu; Aktas, Ilknur

2018-01-01

The purpose of this study was to investigate whether transitional vertebrae contribute to the development of sacroiliac joint dysfunction. The prevalence of transitional vertebrae in patients with lumbar pain was determined during this process, and the prevalence of sacroiliac dysfunction was compared between patients with low back pain and healthy volunteers. 700 subjects, 500 with low back pain and 200 healthy volunteers were included in this study. Five tests were applied to all participants to determine sacroiliac joint dysfunction. Positivity in three tests was regarded as dysfunction. Lateral lumbosacral and Ferguson angle X-rays were taken from the group with low back pain. The patient was evaluated a specialist radiologist in terms of presence or absence of transitional vertebrae, and if identified, what type. Transitional vertebrae were determined in 26% (n = 130) of the patients with low back pain. Type 1a was determined in 20%, type 1b in 10%, type 2a in 26.9%, type 2b in 30.8%, type 3a in 0.8%, type 3b in 4.6% and type 4 in 6.9%. The prevalence of sacroiliac joint dysfunction in the low back pain group (15.4%) and the prevalence of sacroiliac joint dysfunction in cases of transitional vertebra (28.5%) were significantly higher compared to the control groups (p < 0.05). Sacroiliac joint dysfunction must be considered when investigating the etiology of low back pain. Particular sensitivity must be exhibited on this subject in patients with transitional vertebrae.

Photobiomodulation in the Prevention of Tooth Sensitivity Caused by In-Office Dental Bleaching. A Randomized Placebo Preliminary Study.

PubMed

Calheiros, Andrea Paiva Corsetti; Moreira, Maria Stella; Gonçalves, Flávia; Aranha, Ana Cecília Correa; Cunha, Sandra Ribeiro; Steiner-Oliveira, Carolina; Eduardo, Carlos de Paula; Ramalho, Karen Müller

2017-08-01

Analyze the effect of photobiomodulation in the prevention of tooth sensitivity after in-office dental bleaching. Tooth sensitivity is a common clinical consequence of dental bleaching. Therapies for prevention of sensitivity have been investigated in literature. This study was developed as a randomized, placebo blind clinical trial. Fifty patients were selected (n = 10) and randomly divided into five groups: (1) control, (2) placebo, (3) laser before bleaching, (4) laser after bleaching, and (5) laser before and after bleaching. Irradiation was performed perpendicularly, in contact, on each tooth during 10 sec per point in two points. The first point was positioned in the middle of the tooth crown and the second in the periapical region. Photobiomodulation was applied using the following parameters: 780 nm, 40 mW, 10 J/cm 2 , 0.4 J per point. Pain was analyzed before, immediately after, and seven subsequent days after bleaching. Patients were instructed to report pain using the scale: 0 = no tooth sensitivity, 1 = gentle sensitivity, 2 = moderate sensitivity, 3 = severe sensitivity. There were no statistical differences between groups at any time (p > 0.05). More studies, with others parameters and different methods of tooth sensitivity analysis, should be performed to complement the results found. Within the limitation of the present study, the laser parameters of photobiomodulation tested in the present study were not efficient in preventing tooth sensitivity after in-office bleaching.

Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren's Syndrome: Capturing the Discrepancy.

PubMed

Bezzina, Oriana M; Gallagher, Peter; Mitchell, Sheryl; Bowman, Simon J; Griffiths, Bridget; Hindmarsh, Victoria; Hargreaves, Ben; Price, Elizabeth J; Pease, Colin T; Emery, Paul; Lanyon, Peter; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Anne M; Regan, Marian; Giles, Ian P; Isenberg, David A; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil J; Young-Min, Steven A; Moots, Robert J; Gendi, Nagui; Akil, Mohammed; MacKay, Kirsten; Ng, W Fai; Robinson, Lucy J

2017-11-01

To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity. Archive data from the UK Primary Sjögren's Syndrome Registry (n = 688) were used. Patients were classified on a scale from -5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease-related factors, and symptoms of pain, fatigue, anxiety, and depression. Patients were on average relatively stoical for both types of dryness symptoms (mean ± SD ocular dryness -0.42 ± 2.2 and -1.24 ± 1.6 oral dryness). Twenty-seven percent of patients were classified as sensitive to ocular dryness and 9% to oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness sensitivity to be self-reported pain and that of oral dryness sensitivity to be self-reported fatigue. Ocular and oral dryness sensitivity can be classified on a continuous scale. The 2 symptom types are predicted by different variables. A large number of factors remain to be explored that may impact symptom sensitivity in primary Sjögren's syndrome, and the proposed method could be used to identify relatively sensitive and stoical patients for future studies. © 2016, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

An Integrative Neuroscience Framework for the Treatment of Chronic Pain: From Cellular Alterations to Behavior.

PubMed

Greenwald, Jess D; Shafritz, Keith M

2018-01-01

Chronic pain can result from many pain syndromes including complex regional pain syndrome (CRPS), phantom limb pain and chronic low back pain, among others. On a molecular level, chronic pain syndromes arise from hypersensitization within the dorsal horn of the spinal cord, a process known as central sensitization. Central sensitization involves an upregulation of ionotropic and metabotropic glutamate receptors (mGluRs) similar to that of long-term potentiation (LTP). Regions of the brain in which LTP occurs, such as the amygdala and hippocampus, are implicated in fear- and memory-related brain circuity. Chronic pain dramatically influences patient quality of life. Individuals with chronic pain may develop pain-related anxiety and pain-related fear. The syndrome also alters functional connectivity in the default-mode network (DMN) and salience network. On a cellular/molecular level, central sensitization may be reversed through degradative glutamate receptor pathways. This, however, rarely happens. Instead, cortical brain regions may serve in a top-down regulatory capacity for the maintenance or alleviation of pain. Specifically, the medial prefrontal cortex (mPFC), which plays a critical role in fear-related brain circuits, the DMN, and salience network may be the driving forces in this process. On a cellular level, the mPFC may form new neural circuits through LTP that may cause extinction of pre-existing pain pathways found within fear-related brain circuits, the DMN, and salience network. In order to promote new LTP connections between the mPFC and other key brain structures, such as the amygdala and insula, we propose a holistic rehabilitation program including cognitive behavioral therapy (CBT) and revolving around: (1) cognitive reappraisals; (2) mindfulness meditation; and (3) functional rehabilitation. Unlike current medical interventions focusing upon pain-relieving medications, we do not believe that chronic pain treatment should focus on reversing the effects of central sensitization. Instead, we propose here that it is critical to focus on non-invasive efforts to promote new neural circuits originating from the mPFC.

Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

PubMed

Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

2016-03-01

Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest that central sensitization and neuropathic features contribute to NSAID-resistant ongoing OA joint pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Demystifying the Clinical Diagnosis of Greater Trochanteric Pain Syndrome in Women.

PubMed

Ganderton, Charlotte; Semciw, Adam; Cook, Jill; Pizzari, Tania

2017-06-01

To evaluate the diagnostic accuracy of 10 clinical tests that can be used in the diagnosis of greater trochanteric pain syndrome (GTPS) in women, and to compare these clinical tests to magnetic resonance imaging (MRI) findings. Twenty-eight participants with GTPS (49.5 ± 22.0 years) and 18 asymptomatic participants (mean age ± standard deviation [SD], 52.5 ± 22.8 years) were included. A blinded physiotherapist performed 10 pain provocation tests potentially diagnostic for GTPS-palpation of the greater trochanter, resisted external derotation test, modified resisted external derotation test, standard and modified Ober's tests, Patrick's or FABER test, resisted hip abduction, single-leg stance test, and the resisted hip internal rotation test. A sample of 16 symptomatic and 17 asymptomatic women undertook a hip MRI scan. Gluteal tendons were evaluated and categorized as no pathology, mild tendinosis, moderate tendinosis/partial tear, or full-thickness tear. Clinical test analyses show high specificity, high positive predictive value, low to moderate sensitivity, and negative predictive value for most clinical tests. All symptomatic and 88% of asymptomatic participants had pathological gluteal tendon changes on MRI, from mild tendinosis to full-thickness tear. The study found the Patrick's or FABER test, palpation of the greater trochanter, resisted hip abduction, and the resisted external derotation test to have the highest diagnostic test accuracy for GTPS. Tendon pathology on MRI is seen in both symptomatic and asymptomatic women.

Initial accuracy assessment of the modified S-LANSS for the detection of neuropathic orofacial pain conditions.

PubMed

Herrero Babiloni, Alberto; Nixdorf, Donald R; Law, Alan S; Moana-Filho, Estephan J; Shueb, Sarah S; Nguyen, Ruby H; Durham, Justin

2017-01-01

To evaluate the accuracy of a questionnaire modified for the identification of intraoral pain with neuropathic characteristics in a clinical orofacial pain sample population. 136 participants with at least one of four orofacial pain diagnoses (temporomandibular disorders [TMD, n = 41], acute dental pain [ADP, n = 41], trigeminal neuralgia [TN, n = 19], persistent dentoalveolar pain disorder [PDAP, n = 14]) and a group of pain-free controls (n = 21) completed the modified S-LANSS, a previously adapted version of the original questionnaire devised to detected patients suffering from intraoral pain with neuropathic characteristics. Psychometric properties (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) were calculated in two analyses with two different thresholds: (1) Detection of pain with neuropathic characteristics: PDAP + TN were considered positive, and TMD + ADP + controls were considered negative per gold standard (expert opinion). (2) Detection of PDAP: PDAP was considered positive and TMD + ADP were considered negative per gold standard. For both analyses, target values for adequate sensitivity and specificity were defined as ≥ 80%. For detection of orofacial pain with neuropathic characteristics (PDAP + TN), the modified S-LANSS presented with the most optimistic threshold sensitivity of 52% (95% confidence interval [CI], 34-69), specificity of 70% (95% CI, 60-79), PPV of 35% (95% CI, 22-51), and NPV of 82% (95% CI, 72-89). For detection of PDAP only, with the most optimistic threshold sensitivity was 64% (95% CI, 35-87), specificity 63% (95% CI, 52-74), PPV 23% (95% CI, 11-39) and NPV 91% (95% CI, 81-97). Based on a priori defined criteria, the modified S-LANSS did not show adequate accuracy to detect intraoral pain with neuropathic characteristics in a clinical orofacial pain sample.

Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn.

PubMed

Freede, Margaret; Leasure, A Renee; Proskin, Howard M; Hatch, Daniel; Edwards, Karethy; Pascucci, MaryAnn; Smith, Patsy R

2016-01-01

This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific.

A precision medicine approach to a patient with unresolved pain following orthopedic surgery: a case report.

PubMed

Gazzaniga, David; Brenton, Ashley; Meshkin, Brian

2017-02-24

Precision medicine is a promising technology in patient care that combines genetic analysis with clinical data, such as health, behavioral, functional, environment, and lifestyle information. Here we present the case of a 54-year old woman who, following an accident, had uncontrolled chronic pain and was subsequently labeled a drug seeker. A 54-year-old white woman who was experiencing severe calf pain was referred for treatment. Her pain was insufficiently controlled immediately following knee arthroplasty with multiple opioid medications, as well as non-opioids. Precision medicine testing was ordered for her so that we could assess her pain sensitivity objectively to determine if the pill seeker designation was correct and to determine the best medications for her. Based on the Proove profiles, we determined that she had moderately low pain sensitivity, which means that clinically she may underreport pain and may have decreased medication needs. This result suggested that her continued reporting of unresolved pain was probably due to a condition unresolved by her right knee arthroplasty. In addition, she was found to be at low risk of opioid addiction, based on the Proove Opioid Risk Profile. Taken together, along with the high levels of pain she described, we determined that her pain was not properly controlled and that the designation of pill seeker was incorrect. The next step was to determine which medications and which doses would result in the most favorable outcomes for our patient. To determine this, we used the results of the Proove Opioid Response, Proove Drug Metabolism, and Proove Non-Opioid Profiles to guide her treatment. We reduced her pain medications to a single opioid, Vicodin (acetaminophen and hydrocodone), which also eliminated the adverse side effects she experienced. Precision medicine offers an important health care decision tool which can reduce emotional and physical costs to patients and may reduce the economic health care burden of unnecessary surgeries and ineffective medication. The information provided by these profiles can be used clinically to guide treatment decisions and evaluate patient pain.

Systematic mechanism-orientated approach to chronic pancreatitis pain

PubMed Central

Bouwense, Stefan AW; de Vries, Marjan; Schreuder, Luuk TW; Olesen, Søren S; Frøkjær, Jens B; Drewes, Asbjørn M; van Goor, Harry; Wilder-Smith, Oliver HG

2015-01-01

Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders. PMID:25574079

Comparison of Low Back Pain Recovery and Persistence: A Descriptive Study of Characteristics at Pain Onset.

PubMed

Starkweather, Angela R; Lyon, Debra E; Kinser, Patricia; Heineman, Amy; Sturgill, Jamie L; Deng, Xiaoyan; Siangphoe, Umaporn; Elswick, R K; Greenspan, Joel; Dorsey, Susan G

2016-07-01

Persistent low back pain is a significant problem worldwide. Early identification and treatment of individuals at high risk for persistent low back pain have been suggested as strategies to decrease the rate of disability associated with this condition. To examine and compare demographic, pain-related, psychological, and somatosensory characteristics in a cohort of participants with acute low back pain who later went on to experience persistent low back pain or whose pain resolved within the first 6 weeks after initial onset. A descriptive study was conducted among men and women 18-50 years of age who had an acute episode of low back pain. Study questionnaires were administered to collect demographic information and measures of pain, coping, reactivity, mood, work history and satisfaction, and disability. A standardized protocol of quantitative sensory testing was performed on each participant at the painful area of their low back and at a remote site on their arm. The sample consisted of 48 participants, of whom 19 went on to develop persistent low back pain and 29 resolved. Compared to the resolved group, the persistent low back pain group was significantly older and had a lower level of educational attainment, a higher body mass index, and higher mean "least" pain score on the Brief Pain Inventory-Short Form. Significantly higher thermal detection thresholds at the painful and remote sites as well as signs of central sensitivity differentiated the persistent pain group from the resolved group during the acute stage of low back pain. © The Author(s) 2016.

Examining the mediational role of psychological flexibility, pain catastrophizing, and visceral sensitivity in the relationship between psychological distress, irritable bowel symptom frequency, and quality of life.

PubMed

Cassar, G E; Knowles, S; Youssef, G J; Moulding, R; Uiterwijk, D; Waters, L; Austin, D W

2018-06-08

The aim of the current study was to use Structural Equation Modelling (SEM) to examine whether psychological flexibility (i.e. mindfulness, acceptance, valued-living) mediates the relationship between distress, irritable bowel syndrome (IBS) symptom frequency, and quality of life (QoL). Ninety-two individuals participated in the study (12 male, 80 female, M age  = 36.24) by completing an online survey including measures of visceral sensitivity, distress, IBS-related QoL, mindfulness, bowel symptoms, pain catastrophizing, acceptance, and valued-living. A final model with excellent fit was identified. Psychological distress significantly and directly predicted pain catastrophizing, valued-living, and IBS symptom frequency. Pain catastrophizing directly predicted visceral sensitivity and acceptance, while visceral sensitivity significantly and directly predicted IBS symptom frequency and QoL. Symptom frequency also had a direct and significant relationship with QoL. The current findings suggest that interventions designed to address unhelpful cognitive processes related to visceral sensitivity, pain catastrophizing, and psychological distress may be of most benefit to IBS-related QoL.

Translation, Cultural Adaptation, and Validation of Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and Self-Complete Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) Questionnaires into the Greek Language.

PubMed

Batistaki, Chrysanthi; Lyrakos, George; Drachtidi, Kalliopi; Stamatiou, Georgia; Kitsou, Maria-Chrysanthi; Kostopanagiotou, Georgia

2016-06-01

The LANSS and S-LANSS questionnaires represent two widely accepted and validated instruments used to assist the identification of neuropathic pain worldwide. The aim of this study was to translate, culturally adapt, and validate the LANSS and S-LANSS questionnaires into the Greek language. Forward and backward translations of both questionnaires were performed from the English to Greek language. The final versions were assessed by a committee of clinical experts, and they were then pilot-tested in 20 patients with chronic pain. Both questionnaires were validated in 200 patients with chronic pain (100 patients for each questionnaire), using as the "gold standard" the diagnosis of a clinical expert in pain management. Sensitivity and specificity of questionnaires were assessed, as well as the internal consistency (using Cronbach's alpha coefficient) and correlation with the "gold standard" diagnosis (using Pearson correlation coefficient). Sensitivity and specificity of the LANSS questionnaire were calculated to be 82.76% and 95.24%, while for the S-LANSS 86.21% and 95.24%, respectively. Positive predictive value for neuropathic pain was 96% for the LANSS and 96.15% for the S-LANSS. Cronbach's alpha was revealed to be acceptable for both questionnaires (0.65 for LANSS and 0.67 for the S-LANSS), while a significant correlation was observed compared to the "gold standard" diagnosis (rLANSS   = 0.79 και tSLANSS   = 0.77, respectively, P = 0.01). The LANSS and the S-LANSS diagnostic tools have been translated and validated into the Greek language and can be adequately used to assist the identification of neuropathic pain in everyday clinical practice. © 2015 World Institute of Pain.

Detection of osteophytes and subchondral cysts in the knee with use of tomosynthesis.

PubMed

Hayashi, Daichi; Xu, Li; Roemer, Frank W; Hunter, David J; Li, Ling; Katur, Avinash M; Guermazi, Ali

2012-04-01

To evaluate the diagnostic performance of tomosynthesis in depicting osteophytes and subchondral cysts, with use of magnetic resonance (MR) imaging as the reference, and to test whether the lesions detected at radiography and tomosynthesis are associated with pain. The study was approved by local institutional review board, and all subjects gave written informed consent. Forty subjects (80 knees) older than 40 years were recruited irrespective of knee pain or radiographic osteoarthritis. Knees were imaged with radiography, tomosynthesis, and MR imaging. Presence of osteophytes and subchondral cysts in four locations of tibiofemoral joint (medial and lateral femur and tibia) was recorded. Knee pain was assessed by using the Western Ontario and McMaster University pain subscale. MR imaging depicted 171 osteophytes and 51 subchondral cysts. Tomosynthesis had a higher sensitivity for osteophyte detection in left and right lateral femur (0.96 vs 0.75, P = .025, and 1.00 vs 0.71, P = .008, respectively), right medial femur (0.94 vs 0.72, P = .046), and right lateral tibia (1.00 vs 0.83, P = .046). For subchondral cyst detection, the sensitivity of tomosynthesis was 0.14-1.00 and that of radiography was 0.00-0.56. Both modalities had similar specificity for both lesions. Subjects with tomosynthesis-depicted osteophytes (odds ratio, 4.2-6.4; P = .001-.011) and medially located subchondral cysts (odds ratio, 6.7-17.8; P = .004-.03) were more likely to feel pain than those without. However, radiography-depicted osteophytes were more strongly associated with pain than were tomosynthesis-depicted osteophytes. Tomosynthesis depicted more osteophytes and subchondral cysts than did radiography. Subjects with tomosynthesis-depicted osteophytes and subchondral cysts were more likely to feel pain than those without such lesions. © RSNA, 2012.

Increased Evoked Potentials and Behavioral Indices in Response to Pain Among Individuals with Intellectual Disability.

PubMed

Benromano, Tali; Pick, Chaim G; Granovsky, Yelena; Defrin, Ruth

2017-09-01

Previous studies on the sensitivity and reactivity to pain of individuals with intellectual disability (ID) are inconsistent. The inconsistency may result from the reliance on self-reports and facial expressions of pain that are subject to internal and external biases. The aim was therefore to evaluate the reactivity to pain of individuals with ID by recording pain-evoked potentials (EPs), here for the first time, and testing their association with behavioral pain indices. Forty-one healthy adults, 16 with mild-moderate ID and 25 controls. Subjects received series of phasic heat stimuli and rated their pain on self-report scales. Changes in facial expressions and in pain EPs were recorded and analyzed offline. Pain self-reports, facial expressions, and the N2P2 amplitudes of the EPs exhibited stimulus-response relationship with stimulation intensity in both groups. The facial expressions and N2P2 amplitudes of individuals with ID were increased and N2P2 latency prolonged compared with controls. N2P2 amplitudes correlated with self-reports only in controls. Individuals with ID are hypersensitive/reactive to pain, a finding bearing clinical implications. Although pain EPs may reflect a somewhat different aspect of pain than the behavioral indices do, there is evidence to support their use to record pain in noncommunicative individuals, pending further validation. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The role of pain catastrophizing in experimental pain perception.

PubMed

Kristiansen, Frederik L; Olesen, Anne E; Brock, Christina; Gazerani, Parisa; Petrini, Laura; Mogil, Jeffrey S; Drewes, Asbjørn M

2014-03-01

Pain is a subjective experience influenced by multiple factors, and tremendous variety within individuals is present. To evaluate emotional state of pain, catastrophizing score can be used. This study investigated pain catastrophizing ratings in association with experimental pain perception. Experimental pain was induced using thermal heat and cold stimulation of skin, mechanical stimulation of muscle and bone, and thermal, mechanical, and electrical stimulation of the gastrointestinal tract in healthy participants (N = 41). Prior to experimental sessions, a pain catastrophizing questionnaire was filled out by each participant. Based on the median catastophizing score, participants were divided into two groups: noncatastrophizers and low-catastrophizers. No significant difference was found between low-catastrophizers and noncatastrophizers in thermal heat stimulation of skin, mechanical stimulation of muscle and bone, and rectal electrical stimulation (All P > 0.05). Low-catastrophizers were more sensitive to visceral thermal stimulation (4.7%, P = 0.02) and visceral mechanical stimulation (29.7%, P = 0.03). For participants that completed the 120 seconds ice water stimulation, noncatastrophizers reported 13.8% less pain than low-catastrophizers (P = 0.02). A positive correlation between PCS score and pain perception on cold pressor test was found (r = 0.4, P = 0.02). By extrapolating data, further analysis of the total group was performed and no differences (both P > 0.05) were observed. Even small increments in pain catastrophizing score can influence pain perception to deep and tonic stimulations. Catatrophizing may partly explain the variability found in experimental pain studies. © 2013 World Institute of Pain.

The diagnostic value of troponin T testing in the community setting.

PubMed

Planer, David; Leibowitz, David; Paltiel, Ora; Boukhobza, Rina; Lotan, Chaim; Weiss, Teddy A

2006-03-08

Many patients presenting with chest pain to their family physician are referred to the emergency room, in part, due to lack of accurate objective diagnostic tools. This study aimed to assess the diagnostic value of bedside troponin T kit testing in patients presenting with chest pain to their family physician. Prospective, multi-center study. Consecutive subjects with chest pain were recruited from 44 community clinics in Jerusalem. Following clinical assessment by the family physician, qualitative troponin kit testing was performed. Patients with a negative clinical assessment and negative troponin kit were sent home and all others were referred to the emergency room. The final diagnosis at the time of hospital discharge was recorded and telephone follow up was performed after 60 days. Positive predictive value, negative predictive value, sensitivity and specificity of troponin kit for myocardial infarction diagnosis and of family physician for hospitalization, were assessed. Of 392 patients enrolled, 349 (89%) were included in the final analysis. The prevalence of myocardial infarction was 1.7%. The positive and negative predictive values of the troponin kit for myocardial infarction diagnosis were 100% and 99.7%, respectively. The positive and negative predictive values of the family physician's assessment to predict hospitalization were 41.4% and 94.1%, respectively. Troponin kit testing is an important tool to assist the family physician in the assessment of patients with chest pain in the community setting. Troponin kit testing may identify otherwise undiagnosed cases of myocardial infarctions, and reduce unnecessary referrals to the emergency room.

Joint Mobilization Enhances Mechanisms of Conditioned Pain Modulation in Individuals With Osteoarthritis of the Knee.

PubMed

Courtney, Carol A; Steffen, Alana D; Fernández-de-Las-Peñas, César; Kim, John; Chmell, Samuel J

2016-03-01

An experimental laboratory study with a repeated-measures crossover design. Treatment effects of joint mobilization may occur in part by decreasing excitability of central nociceptive pathways. Impaired conditioned pain modulation (CPM) has been found experimentally in persons with knee and hip osteoarthritis, indicating impaired inhibition of central nociceptive pathways. We hypothesized increased effectiveness of CPM following application of joint mobilization, determined via measures of deep tissue hyperalgesia. To examine the effect of joint mobilization on impaired CPM. An examination of 40 individuals with moderate/severe knee osteoarthritis identified 29 (73%) with impaired CPM. The subjects were randomized to receive 6 minutes of knee joint mobilization (intervention) or manual cutaneous input only, 1 week apart. Deep tissue hyperalgesia was examined via pressure pain thresholds bilaterally at the knee medial joint line and the hand at baseline, postintervention, and post-CPM testing. Further, vibration perception threshold was measured at the medial knee epicondyle at baseline and post-CPM testing. Joint mobilization, but not cutaneous input intervention, resulted in a global increase in pressure pain threshold, indicated by diminished hyperalgesic responses to pressure stimulus. Further, CPM was significantly enhanced following joint mobilization. Diminished baseline vibration perception threshold acuity was enhanced following joint mobilization at the knee that received intervention, but not at the contralateral knee. Resting pain was also significantly lower following the joint intervention. Conditioned pain modulation was enhanced following joint mobilization, demonstrated by a global decrease in deep tissue pressure sensitivity. Joint mobilization may act via enhancement of descending pain mechanisms in patients with painful knee osteoarthritis.

Multiple Nonspecific Sites of Joint Pain Outside the Knees Develop in Persons With Knee Pain.

PubMed

Felson, David T; Niu, Jingbo; Quinn, Emily K; Neogi, Tuhina; Lewis, Cara L; Lewis, Cora E; Frey Law, Laura; McCulloch, Chuck; Nevitt, Michael; LaValley, Michael

2017-02-01

Many persons with knee pain have joint pain outside the knee, but despite the impact and high frequency of this pain, its distribution and causes have not been studied. We undertook this study to test the hypothesis of those studying gait abnormalities who have suggested that knee pain causes pain in adjacent joints but that pain adaptation strategies are highly individualized. We studied persons ages 50-79 years with or at high risk of knee osteoarthritis who were recruited from 2 community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative, and we followed them up for 5-7 years. We excluded those with knee pain at baseline and compared those who had developed knee pain at the first follow-up examination (the index visit) with those who had not. We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint-specific pain adjusted for age, sex, body mass index, and symptoms of depression, and we performed sensitivity analyses excluding those with widespread pain. In the combined cohorts, 693 persons had knee pain at the index visit and 2,793 did not. A total of 79.6% of those with bilateral knee pain and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee, compared with 49.9% of those without knee pain. There was an increased risk of pain at most extremity joint sites, without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded. Persons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern. © 2016, American College of Rheumatology.

Masticatory muscle and temporomandibular joint pain in Croatian war veterans with posttraumatic stress disorder.

PubMed

Uhac, Ivone; Tariba, Petra; Kovac, Zoran; Simonić-Kocijan, Suncana; Lajnert, Vlatka; Mesić, Vesna Fugosić; Kuis, Davor; Braut, Vedrana

2011-12-01

The aim of this study was to investigate the prevalence and intensity of masticatory muscle and temporomandibular joint (TMJ) pain in Croatian war veterans with posttraumatic stress disorder (PTSD). The examined group consisted of 100 Croatian war veterans, in whom PTSD had previously been diagnosed. Patients were compared with 92 subjects who had not taken part in the war and in whom PTSD was excluded by psychiatric examination. The clinical examination consisted of palpation of the masticatory muscles, the prominent neck musculature, and TMJ. The examination technique used and the definition of items were previously tested for reliability and validity. 93% of the subjects with PTSD had masticatory muscle tenderness compared to 45.65% of the subjects in the control group (chi2 = 51.46, p < 0.0001). The most frequent painful location in the subjects with PTSD was the left lateral pterygoid site in 88%, and in subjects of the control group the right lateral pterygoid site in 28.26% of cases. The most painful location in the PTSD group was the left lateral pterygoid site in 72%, and in the control group the left posterior digastric in 4.35% of cases. 58% of the subjects with PTSD had TMJ tenderness compared to 3.26% of subjects in the control group (chi2 = 66.23, p < 0.0001). The most frequent painful location of TMJ in both groups was the left posterior capsule; in the PTSD group 38% and in subjects in the control group 2.17% of cases. The most painful location was the left posterior capsule in 28% of subjects with PTSD, while not one subject in the control group reported severe painful sensitivity. The very high frequency and intensity of pain in subjects with PTSD confirms the effect of stress on muscle and joint sensitivity, i.e. perception of pain.

Clinical presentation and manual therapy for lower quadrant musculoskeletal conditions.

PubMed

Courtney, Carol A; Clark, Jeffrey D; Duncombe, Alison M; O'Hearn, Michael A

2011-11-01

Chronic lower quadrant injuries constitute a significant percentage of the musculoskeletal cases seen by clinicians. While impairments may vary, pain is often the factor that compels the patient to seek medical attention. Traumatic injury from sport is one cause of progressive chronic joint pain, particularly in the lower quarter. Recent studies have demonstrated the presence of peripheral and central sensitization mechanisms in different lower quadrant pain syndromes, such as lumbar spine related leg pain, osteoarthritis of the knee, and following acute injuries such as lateral ankle sprain and anterior cruciate ligament rupture. Proper management of lower quarter conditions should include assessment of balance and gait as increasing pain and chronicity may lead to altered gait patterns and falls. In addition, quantitative sensory testing may provide insight into pain mechanisms which affect management and prognosis of musculoskeletal conditions. Studies have demonstrated analgesic effects and modulation of spinal excitability with use of manual therapy techniques, with clinical outcomes of improved gait and functional ability. This paper will discuss the evidence which supports the use of manual therapy for lower quarter musculoskeletal dysfunction.

The approach to patients with possible cardiac chest pain.

PubMed

Parsonage, William A; Cullen, Louise; Younger, John F

2013-07-08

Chest pain is a common reason for presentation in hospital emergency departments and general practice. Some patients presenting with chest pain to emergency departments and, to a lesser extent, general practice will be found to have a life-threatening cause, but most will not. The challenge is to identify those who do in a safe, timely and cost-effective manner. An acute coronary syndrome cannot be excluded on clinical grounds alone. In patients with ongoing symptoms of chest pain, without an obvious other cause, ST-segment-elevation myocardial infarction should be excluded with a 12-lead electrocardiogram at the first available opportunity. Significant recent advances in the clinical approach to patients with acute chest pain, including better understanding of risk stratification, increasingly sensitive cardiac biomarkers and new non-invasive tests for coronary disease, can help clinicians minimise the risk of unexpected short-term adverse cardiac events. An approach that integrates these advances is needed to deliver the best outcomes for patients with chest pain. All hospital emergency departments should adopt such a strategic approach, and general practitioners should be aware of when and how to access these facilities.

Glial pannexin1 contributes to tactile hypersensitivity in a mouse model of orofacial pain

PubMed Central

Hanstein, Regina; Hanani, Menachem; Scemes, Eliana; Spray, David C.

2016-01-01

Drug studies in animal models have implicated pannexin1 (Panx1) in various types of pain, including trigeminal hypersensitivity, neuropathic pain and migraine. However, the tested drugs have limited specificity and efficacy so that direct evidence for Panx1 contribution to pain has been lacking. We here show that tactile hypersensitivity is markedly attenuated by deletion of Panx1 in a mouse model of chronic orofacial pain; in this model, trigeminal ganglion Panx1 expression and function are markedly enhanced. Targeted deletion of Panx1 in GFAP-positive glia or in neurons revealed distinct effects. Panx1 deletion in GFAP-positive glia cells prevented hypersensitivity completely, whereas deletion of neuronal Panx1 reduced baseline sensitivity and the duration of hypersensitivity. In trigeminal ganglia with genetically encoded Ca2+ indicator in GFAP-positive glia or in neurons, both cell populations were found to be hyperactive and hyper-responsive to ATP. These novel findings reveal unique roles for GFAP-positive glial and neuronal Panx1 and describe new chronic pain targets for cell-type specific intervention in this often intractable disease. PMID:27910899

Complex Regional Pain Syndrome

MedlinePlus

Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. ... in skin temperature, color, or texture Intense burning pain Extreme skin sensitivity Swelling and stiffness in affected ...

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses

PubMed Central

Low, Lucie A.; Bauer, Lucy C.; Pitcher, Mark H.; Bushnell, M. Catherine

2016-01-01

Abstract With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the “nociceptive” central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli. PMID:27058679

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

PubMed

Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H; Bushnell, M Catherine

2016-08-01

With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.

Evaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models - the TapCapMentho pilot trial.

PubMed

Förster, M; Helfert, S; Dierschke, R; Großkopf, M; Hüllemann, P; Keller, T; Baron, R; Binder, A

2016-09-01

Tapentadol is effective in the treatment of neuropathic and nociceptive pain and in acute and chronic pain conditions; two mechanisms combining opioid µ-receptor agonism and noradrenergic reuptake inhibition underlie its analgesic effect. With this single-center, placebo-controlled, double-blind, cross-over pilot-study, we investigated the antihyperalgesic effect of a single oral dose of 100 mg immediate-release tapentadol on thermal and mechanical hyperalgesia in two human models (i.e. 0.6 % topical capsaicin and 40% topical menthol) of evoked neuropathic pain signs in healthy volunteers. No significant differences regarding experimentally induced heat or cold and mechanical (pinprick) hyperalgesia, as assessed by quantitative sensory testing, could be observed between a single dose of drug and placebo (thermal pain thresholds p>0.4, mechanical pain sensitivity p>0.1). Only few mild side effects of tapentadol were reported. The discrepancy between pain models using healthy volunteers and drug trials under real acute and chronic pain conditions in patients as well as methodological aspects may have contributed to this result. The impact of these findings questions the general use of pain models as predictors for early decision making during drug development. The study was registered in ClinicalTrials.gov (NCT01615510).

Analgesia for early-life pain prevents deficits in adult anxiety and stress in rats.

PubMed

Victoria, Nicole C; Karom, Mary C; Murphy, Anne Z

2015-01-01

Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants. © 2014 S. Karger AG, Basel.

Reliability and relationship of the fear-avoidance beliefs questionnaire with the shoulder pain and disability index and numeric pain rating scale in patients with shoulder pain.

PubMed

Riley, Sean P; Tafuto, Vincent; Cote, Mark; Brismée, Jean-Michel; Wright, Alexis; Cook, Chad

2018-03-20

The purpose of this study was to determine: 1) the test-retest reliability of Fear-Avoidance Beliefs Questionnaire (FABQ) Work (FABQW) subscale, FABQ Physical Activity (FABQPA) subscale, Shoulder Pain and Disability Index (SPADI) Pain subscale, SPADI Disability subscale, and Numeric Pain Rating scale (NPRS); and 2) the relationship between the FABQPA, FABQW, SPADI pain, SPADI disability, and NPRS after 4 weeks of pragmatically applied physical therapy (PT) in patients with shoulder pain. Prospective, single-group observational design. Data were collected at initial evaluation, the first follow-up visit prior to the initiation of treatment, and after 4 weeks of treatment. Statistically significant Intraclass Correlation Coefficient (ICC 2,1 ) values were reported for the FABQPA, FABQW, SPADI Pain, SPADI Disability, and NPRS. A statistically significant moderate relationship between the FABQPA subscale, SPADI subscale, and NPRS could not be established prior to and after 4 weeks of pragmatically applied PT. Statistically significant differences were observed between the initial evaluation and four-week follow-up for the FABQPA, SPADI Pain, SPADI Disability, and NPRS (p < 0.01). Since a meaningful relationship between the FABQ, SPADI, and NPRS did not exist, it suggests that the FABQPA may be measuring a metric other than pain. This study suggests that the FABQW may not be sensitive to change over time.

Analgesic effects of the COX-2 inhibitor parecoxib on surgical pain through suppression of spinal ERK signaling.

PubMed

Guo, Ya-Jing; Shi, Xu-Dan; Fu, DI; Yang, Yong; Wang, Ya-Ping; Dai, Ru-Ping

2013-07-01

Cyclooxygenase (COX)-2 inhibitors are widely used for postoperative pain control in clinical practice. However, it is unknown whether spinal sensitization is involved in the analgesic effects of COX-2 inhibitors on surgical pain. Extracellular signal-regulated kinase (ERK) in the spinal cord is implicated in various types of pain, including surgical pain. The present study investigated the role of spinal ERK signaling in the analgesic effect of the COX-2 inhibitor parecoxib on surgical pain. Surgical pain was produced in rats by surgical incision of the hind paw. Phosphorylated (p)-ERK1/2 expression was determined by immunohistochemistry. Pain hypersensitivity was evaluated by measuring the paw withdrawal threshold using the von Frey test. The selective COX-2 inhibitor parecoxib was delivered 20 min before or 20 min after the incision by intraperitoneal injection. Pretreatment with parecoxib markedly attenuated the pain hypersensitivity induced by incision. However, post-treatment with parecoxib produced minimal analgesic effects. Parecoxib inhibited the increase in spinal p-ERK expression following surgical incision. The present study thus suggests that the COX-2 inhibitor parecoxib exerts its analgesic effect on surgical pain through the inhibition of neuronal ERK activation in the spinal cord. COX-2 inhibitor delivery prior to surgery has more potent analgesic effects, suggesting the advantage of preventive analgesia for post-operative pain control.

Acute psychosocial stress reduces pain modulation capabilities in healthy men.

PubMed

Geva, Nirit; Pruessner, Jens; Defrin, Ruth

2014-11-01

Anecdotes on the ability of individuals to continue to function under stressful conditions despite injuries causing excruciating pain suggest that acute stress may induce analgesia. However, studies exploring the effect of acute experimental stress on pain perception show inconsistent results, possibly due to methodological differences. Our aim was to systematically study the effect of acute stress on pain perception using static and dynamic, state-of-the-art pain measurements. Participants were 29 healthy men who underwent the measurement of heat-pain threshold, heat-pain intolerance, temporal summation of pain, and conditioned pain modulation (CPM). Testing was conducted before and during exposure to the Montreal Imaging Stress Task (MIST), inducing acute psychosocial stress. Stress levels were evaluated using perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol. The MIST induced a significant stress reaction. Although pain threshold and pain intolerance were unaffected by stress, an increase in temporal summation of pain and a decrease in CPM were observed. These changes were significantly more robust among individuals with stronger reaction to stress ("high responders"), with a significant correlation between the perception of stress and the performance in the pain measurements. We conclude that acute psychosocial stress seems not to affect the sensitivity to pain, however, it significantly reduces the ability to modulate pain in a dose-response manner. Considering the diverse effects of stress in this and other studies, it appears that the type of stress and the magnitude of its appraisal determine its interactions with the pain system. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Convergent validity evidence for the Pain and Discomfort Scale (PADS) for pain assessment among adults with intellectual disability

PubMed Central

Shinde, Satomi K.; Danov, Stacy; Chen, Chin-Chih; Clary, Jamie; Harper, Vicki; Bodfish, James W.; Symons, Frank J.

2014-01-01

Objectives The main aim of the study was to generate initial convergent validity evidence for the Pain and Discomfort Scale (PADS) for use with non-verbal adults with intellectual disabilities (ID). Methods Forty-four adults with intellectual disability (mean age = 46, 52 % male) were evaluated using a standardized sham-controlled and blinded sensory testing protocol, from which FACS and PADS scores were tested for (1) sensitivity to an array of calibrated sensory stimuli, (2) specificity (active vs. sham trials), and (3) concordance. Results The primary findings were that participants were reliably coded using both FACS and PADS approaches as being reactive to the sensory stimuli (FACS: F[2, 86] = 4.71, P < .05, PADS: F[2, 86] = 21.49, P < .05) (sensitivity evidence), not reactive during the sham stimulus trials (FACS: F[1, 43]= 3.77, p = .06, PADS: F[1, 43] = 5.87, p = .02) (specificity evidence), and there were significant (r = .41 – .51, p < .01) correlations between PADS and FACS (convergent validity evidence). Discussion FACS is an objective coding platform for facial expression. It requires intensive training and resources for scoring. As such it may be limited for clinical application. PADS was designed for clinical application. PADS scores were comparable to FACS scores under controlled evaluation conditions providing partial convergent validity evidence for its use. PMID:24135902

Effectiveness of manual therapy versus surgery in pain processing due to carpal tunnel syndrome: A randomized clinical trial.

PubMed

Fernández-de-Las-Peñas, C; Cleland, J; Palacios-Ceña, M; Fuensalida-Novo, S; Alonso-Blanco, C; Pareja, J A; Alburquerque-Sendín, F

2017-08-01

People with carpal tunnel syndrome (CTS) exhibit widespread pressure pain and thermal pain hypersensitivity as a manifestation of central sensitization. The aim of our study was to compare the effectiveness of manual therapy versus surgery for improving pain and nociceptive gain processing in people with CTS. The trial was conducted at a local regional Hospital in Madrid, Spain from August 2014 to February 2015. In this randomized parallel-group, blinded, clinical trial, 100 women with CTS were randomly allocated to either manual therapy (n = 50), who received three sessions (once/week) of manual therapies including desensitization manoeuvres of the central nervous system, or surgical intervention (n = 50) group. Outcomes including pressure pain thresholds (PPT), thermal pain thresholds (HPT or CPT), and pain intensity which were assessed at baseline, and 3, 6, 9 and 12 months after the intervention by an assessor unaware of group assignment. Analysis was by intention to treat with mixed ANCOVAs adjusted for baseline scores. At 12 months, 95 women completed the follow-up. Patients receiving manual therapy exhibited higher increases in PPT over the carpal tunnel at 3, 6 and 9 months (all, p < 0.01) and higher decrease of pain intensity at 3 month follow-up (p < 0.001) than those receiving surgery. No significant differences were observed between groups for the remaining outcomes. Manual therapy and surgery have similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with CTS. Neither manual therapy nor surgery resulted in changes in thermal pain sensitivity. The current study found that manual therapy and surgery exhibited similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with carpal tunnel syndrome at medium- and long-term follow-ups investigating changes in nociceptive gain processing after treatment in carpal tunnel syndrome. © 2017 European Pain Federation - EFIC®.

From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing-an exploratory study.

PubMed

Marcuzzi, Anna; Wrigley, Paul J; Dean, Catherine M; Graham, Petra L; Hush, Julia M

2018-03-01

Chronic low back pain (LBP) is commonly associated with generalised pain hypersensitivity. It is suggested that such somatosensory alterations are important determinants for the transition to persistent pain from an acute episode of LBP. Although cross-sectional research investigating somatosensory function in the acute stage is developing, no longitudinal studies designed to evaluate temporal changes have been published. This exploratory study aimed to investigate the temporal development of somatosensory changes from the acute stage of LBP to up to 4 months from onset. Twenty-five people with acute LBP (<3 weeks' duration) and 48 pain-free controls were prospectively assessed at baseline using quantitative sensory testing with the assessor blinded to group allocation, and again at 2 and 4 months. Psychological variables were concurrently assessed. People with acute LBP were classified based on their average pain severity over the previous week at 4 months as recovered (≤1/10 numeric rating scale) or persistent (≥2/10 numeric rating scale) LBP. In the persistent LBP group, (1) there was a significant decrease in pressure pain threshold between 2 and 4 months ( P < 0.013), and at 4 months, pressure pain threshold was significantly different from the recovered LBP group ( P < 0.001); (2) a trend towards increased temporal summation was found at 2 months and 4 months, at which point it exceeded 2 SDs beyond the pain-free control reference value. Pain-related psychological variables were significantly higher in those with persistent LBP compared with the recovered LBP group at all time points ( P < 0.05). Changes in mechanical pain sensitivity occurring in the subacute stage warrant further longitudinal evaluation to better understand the role of somatosensory changes in the development of persistent LBP. Pain-related cognitions at baseline distinguished persistent from the recovered LBP groups, emphasizing the importance of concurrent evaluation of psychological contributors in acute LBP.

Cognitive, psychophysical, and neural correlates of vulvar pain in primary and secondary provoked vestibulodynia: a pilot study.

PubMed

Sutton, Katherine; Pukall, Caroline; Wild, Conor; Johnsrude, Ingrid; Chamberlain, Susan

2015-05-01

Provoked vestibulodynia (PVD) is a common condition characterized by localized, provoked pain that can be present since first vaginal penetration attempt (primary) or can develop after a period of pain-free penetration (secondary). Research has demonstrated psychosocial and psychophysical differences between women with these subtypes of PVD, but the question of whether neural responses to pain also differ remains to be investigated. This study aims to examine whether cognitive, psychophysical, and neural responses to vulvar pressure pain differ between women with PVD1 and PVD2. Women with PVD1 and PVD2 were compared for group differences using multiple modalities, including questionnaires, psychophysical testing, and neuroimaging. Pain ratings were held constant across groups, rather than amount of pressure applied. Demographics, sexual functioning, four questionnaires examining anxiety and catastrophizing, quantitative sensory testing at the vulvar vestibule using a vulvalgesiometer, and functional and structural magnetic resonance imaging (MRI). Findings suggest that women with PVD1 are more anxious and that they catastrophize more about their vulvar and nonvulvar pain than women with PVD2. Overall, MRI results demonstrated structural and functional similarities to other chronic pain findings for both groups of women. Gray matter (GM) density also differed between groups: women with PVD1 showed significant decreases in GM throughout areas associated with pain processing. Functionally, between-groups differences were found during painful vulvar stimulation despite lower pressures applied to the vulva for women with PVD1 because of their heightened sensitivity; the determination of the level of vulvar pressure to elicit pain was based on subjective ratings. Findings are limited by sample size and liberal alpha values; however, future research is certainly warranted based on the preliminary findings of this study suggesting both similarities and differences between PVD1 and PVD2. Overall, women with PVD1 seem to fare worse on several pain-related and psychosocial variables compared with women with PVD2. © 2015 International Society for Sexual Medicine.

Systematic review of the quality and generalizability of studies on the effects of opioids on driving and cognitive/psychomotor performance.

PubMed

Mailis-Gagnon, Angela; Lakha, Shehnaz Fatima; Furlan, Andrea; Nicholson, Keith; Yegneswaran, Balaji; Sabatowski, Rainer

2012-07-01

The effect of opioids on driving performance has been much debated. Driving is a complex task requiring integration of psychomotor, cognitive, motor and decision-making skills, visual-spatial abilities, divided attention, and behavioral and emotional control. The objective of this systematic review was to assess the quality of studies and to revisit the concept that patients on stable opioids are safe to drive as it applies to everyday practice. We searched MEDLINE, EMBASE, PSYCinfo, CENTRAL, TRANSPORT, CINAHL, reference lists of retrieved articles and narrative reviews, for studies on chronic cancer and noncancer pain patients on opioids, tested by driving, driving simulator, or cognitive/psychomotor tests. Methodological quality was assessed with Methodological Index for Nonrandomized Studies, cognitive/psychomotor tests were appraised regarding their sensitivity and validation, and whether confounding variables potentially affecting the study conclusions were recorded. The results were analyzed both quantitatively and qualitatively. We included 35 studies (2044 patients, 1994 controls), 9% of the studies were of poor, 54% of fair, and 37% of high quality; 3 quarters of the studies used high sensitivity cognitive tests. Amount and dose of opioids varied largely in many studies. Mean number of possible but unreported confounders was 2.2 (range, 0 to 4), relating to failure of the studies to mention co-prescriptions with psychotropic effects, pain severity, sleep disorder or daytime somnolence, and/or significant depressive or anxiety-related problems. The commonly held concept that "chronic pain patients on stable opioids are safe to drive" cannot be generalized to all such patients in everyday practice, but may be applicable only to a subset who meet certain criteria.

Understanding the role of injury/illness sensitivity and anxiety sensitivity in (automatic) pain processing: an examination using the extrinsic affective simon task.

PubMed

Vancleef, Linda M G; Peters, Madelon L; Gilissen, Susan M P; De Jong, Peter J

2007-07-01

Three fundamental fears are assumed to underlie psychopathology: Anxiety Sensitivity (AS), Injury/illness sensitivity (IS), and Fear of Negative Evaluation (FNE). Both AS and IS may form risk factors for the development and exacerbation of chronic pain. The current research examines the relation between these fears and automatic threat appraisal for pain-related stimuli. Study 1 (n=48) additionally examined content-specific associations of AS and FNE with the automatic threat appraisal of, respectively, panic and social evaluative cues. Study 2 (n=60) additionally focused on the association of IS and AS with the engagement in health protecting behavior, and the use of health care services. Both studies found evidence for an automatic threat appraisal of aversive stimuli. Study 2 demonstrated a positive association between the automatic threat appraisal for pain-related stimuli and individuals' IS levels. IS was found to be the single best predictor of the tendency to engage in health protecting behavior, whereas AS was the single best predictor of the reported use of health care services. This study contributes to the field of knowledge on putative risk factors for chronic pain. Results demonstrate an automatic threat appraisal toward pain-related stimuli that is related to vulnerability traits for pain. This automatic threat appraisal might initiate relatively spontaneous (nonstrategic) pain-maintaining behavioral responses.

Cognitive load selectively influences the interruptive effect of pain on attention.

PubMed

Moore, David J; Eccleston, Christopher; Keogh, Edmund

2017-10-01

Pain is known to interrupt attentional performance. Such interference effects seem to occur preferentially for tasks that are complex and/or difficult. However, few studies have directly manipulated memory load in the context of pain interference to test this view. Therefore, this study examines the effect of experimental manipulations of both memory load and pain on 3 tasks previously found to be sensitive to pain interference. Three experiments were conducted. A different task was examined in each experiment, each comprising of a high- and low-cognitive load versions of the task. Experiment 1 comprised an attention span (n-back) task, experiment 2 an attention switching task, and experiment 3 a divided attention task. Each task was conducted under painful and nonpainful conditions. Within the pain condition, an experimental thermal pain induction protocol was administered at the same time participants completed the task. The load manipulations were successful in all experiments. Pain-related interference occurred under the high-load condition but only for the attention span task. No effect of pain was found on either the attentional switching or divided attention task. These results suggest that while cognitive load may influence the interruptive effect of pain on attention, this effect may be selective. Because pain affected the high-load version of the n-back task but did not interrupt performance on attentional switching or dual-task paradigms, this means that our findings did not completely support our hypotheses. Future research should explore further the parameters and conditions under which pain-related interference occurs.

Cross-Cultural Psychometric Assessment of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale in the Portuguese Population.

PubMed

Barbosa, Margarida; Bennett, Michael I; Verissimo, Ramiro; Carvalho, Davide

2014-09-01

Chronic pain is a well-known phenomenon. The differential diagnosis between neuropathic and nociceptive pain syndromes is a challenge. Consequently, assessment instruments that can distinguish between these conditions in a standardized way are of the utmost importance. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) is a screening tool developed to identify chronic neuropathic pain. The aim of this study was the Portuguese language translation, linguistic adaptation of the LANSS pain scale, its semantic validation, internal consistency, temporal stability, as well its validity and discriminative power. LANSS Portuguese version scale was applied to 165 consecutive patients attending the pain clinic: 103 fulfilled the clinical criteria for the diagnosis of pain of neuropathic origin and the remaining 62 fulfilled the criteria for nociceptive pain. The scale proved to be an internally consistent (Cronbach's alpha = 0.78) and reliable instrument with good test-retest stability (r = 0.7; P < 0.001). However, its validity and specificity with a cutoff point of ≥ 12, for differentiating patients with neuropathic pain from those with non-neuropathic pain, had 89% sensitivity, 74% specificity, positive predictive value of 85%, and negative predictive value of 81%. The Portuguese LANSS version pain scale properties lead us to the conclusion that such a cross-cultural version is a reliable and valid instrument for the differentiation of this type of pain. Its usage is recommended. © 2013 World Institute of Pain.

Triathletes Lose Their Advantageous Pain Modulation under Acute Psychosocial Stress.

PubMed

Geva, Nirit; Pruessner, Jens; Defrin, Ruth

2017-02-01

Triathletes, who constantly engage in intensely stressful sport, were recently found to exhibit greater pain tolerance and more efficient pain inhibition capabilities than nonathletes. However, pain inhibition correlated negatively with retrospective reports of mental stress during training and competition. The aim of the current study was to test pain inhibition capabilities of triathletes under acute, controlled psychological stress manipulation. Participants were 25 triathletes and ironman triathletes who underwent the measurement of pain threshold, pain intolerance, tonic suprathreshold pain, and conditioned pain modulation before and during exposure to the Montreal Imaging Stress Task (MIST). Perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol levels were obtained as indices of stress. The MIST induced a significant stress reaction manifested in the subjective and objective indices. Overall, a significant reduction in pain threshold and in conditioned pain modulation efficacy was observed after the MIST, which reached the baseline levels observed previously in nonathletes. Paradoxically, the magnitude of this stress-induced hyperalgesia (SIH) correlated negatively with the magnitude of the stress response; low-stress responders exhibited greater SIH than high-stress responders. The results suggest that under acute psychological stress, triathletes not only react with SIH and a reduction in pain modulation but also lose their advantageous pain modulation over nonathletes. The stronger the stress response recorded, the weaker the SIH. It appears that triathletes are not resilient to stress, responding with an increase in the sensitivity to pain as well as a decrease in pain inhibition. The possible effects of athletes' baseline pain profile and stress reactivity on SIH are discussed.

Cancer Pain: A Critical Review of Mechanism-based Classification and Physical Therapy Management in Palliative Care

PubMed Central

Kumar, Senthil P

2011-01-01

Mechanism-based classification and physical therapy management of pain is essential to effectively manage painful symptoms in patients attending palliative care. The objective of this review is to provide a detailed review of mechanism-based classification and physical therapy management of patients with cancer pain. Cancer pain can be classified based upon pain symptoms, pain mechanisms and pain syndromes. Classification based upon mechanisms not only addresses the underlying pathophysiology but also provides us with an understanding behind patient's symptoms and treatment responses. Existing evidence suggests that the five mechanisms – central sensitization, peripheral sensitization, sympathetically maintained pain, nociceptive and cognitive-affective – operate in patients with cancer pain. Summary of studies showing evidence for physical therapy treatment methods for cancer pain follows with suggested therapeutic implications. Effective palliative physical therapy care using a mechanism-based classification model should be tailored to suit each patient's findings, using a biopsychosocial model of pain. PMID:21976851

Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: a MAPP Research Network study.

PubMed

Schrepf, Andrew; Williams, David A; Gallop, Robert; Naliboff, Bruce; Basu, Neil; Kaplan, Chelsea; Harper, Daniel E; Landis, Richard; Clemens, J Quentin; Strachan, Eric; Griffith, James W; Afari, Niloofar; Hassett, Afton; Pontari, Michel A; Clauw, Daniel J; Harte, Steven E

2018-05-28

Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This 'centralized pain' phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here we used three cohorts, including patients with Urologic Chronic Pelvic Pain Syndrome (UCPPS), a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified two general factors in all three cohorts, one characterized by a broad increased sensitivity to internal somatic sensations and environmental stimuli, and diffuse pain, termed Generalized Sensory Sensitivity (GSS), and one characterized by constitutional symptoms - Sleep, Pain, Affect, Cognition, Energy (SPACE). Longitudinal analyses in the UCPPS cohort found the same two factor structure at month six and one year, suggesting that the two factor structure is reproducible over time. In secondary analyses we found that GSS particularly is associated with the presence of comorbid COPCs, while SPACE shows modest associations with measures of disability and urinary symptoms. These factors may represent important and distinct continuum of symptoms that are indicative of the centralized pain phenotype at high levels. Future research of COPCs should accommodate the measurement of each factor.

Conditioned Pain Modulation and Situational Pain Catastrophizing as Preoperative Predictors of Pain following Chest Wall Surgery: A Prospective Observational Cohort Study

PubMed Central

Grosen, Kasper; Vase, Lene; Pilegaard, Hans K.; Pfeiffer-Jensen, Mogens; Drewes, Asbjørn M.

2014-01-01

Background Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency. Methods Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively. Results Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001). Conclusions Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have important implications for developing strategies to treat or prevent acute postoperative pain in selected patients. Pain may be predicted and the malfunctioning pain inhibition mechanism as tested with CPM may be treated with suitable drugs augmenting descending inhibition. PMID:24587268

Gender differences in pain: do emotions play a role?

PubMed

Rhudy, Jamie L; Williams, Amy E

2005-12-01

Research suggests that the influence of gender on the processing and experience of pain is a result of several mechanisms. One mediating variable is emotion, which may modulate pain through an interaction of valence (pleasant-unpleasant) and arousal (calm-excited). This review examines whether gender differences in the experience and processing of emotion contribute to differences in the modulation and perception of pain. An English-language search of MEDLINE and PsycINFO was conducted from 1887 to May 2005. Additional literature was obtained from reference lists of articles retained in the initial search. Emotion appears to influence pain through a valence-by-arousal interaction. Specifically, negatively valenced emotions with low to moderate arousal (eg, anxiety) enhance pain, whereas negatively valenced emotions with high arousal (eg, fear) reduce pain. In contrast, positively valenced emotions always reduce pain, as long as minimal arousal is achieved. Some evidence suggests that women are more sensitive than men to threat-related stimuli and thus experience more negative affect than men. This would generally lead to enhanced pain perception in women. It is also possible that women are more likely than men to experience negative affect with high arousal (intense fear) and thus pain inhibition. However, the relatively lower base rate of intense negative emotions is not likely to contribute much to gender differences in pain. Evidence also suggests that men may be more sensitive to positive events, particularly sexual/erotic stimuli, which may lead to more positive emotion-induced pain reduction in men, relative to women. This review suggests that gender differences in the experience of pain may arise from differences in the experience and processing of emotion that, in turn, differentially alter pain processing. Specifically, the system associated with negative affect may be more attuned to threatening stimuli in women, and the system associated with positive affect may be more attuned to pleasurable stimuli in men. However, there is a paucity of research directly addressing this issue; much of the research on this topic has failed to test a comprehensive model of emotion, failed to use adequate manipulation checks, or failed to use within-subject experimental designs that control for intra- and interindividual differences. Therefore, it is concluded that additional research is warranted.

Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic pain and disinhibition of the spinal nociceptive circuitry.

PubMed

Ge, Yanhu; Jiao, Yingfu; Li, Peiying; Xiang, Zhenghua; Li, Zhi; Wang, Long; Li, Wenqian; Gao, Hao; Shao, Jiayun; Wen, Daxiang; Yu, Weifeng

2018-05-01

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

PubMed

Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Trunk postural adjustments: Medium-term reliability and correlation with changes of clinical outcomes following an 8-week lumbar stabilization exercise program.

PubMed

Boucher, Jean-Alexandre; Preuss, Richard; Henry, Sharon M; Nugent, Marilee; Larivière, Christian

2018-04-22

Low back pain (LBP) has been previously associated with delayed anticipatory postural adjustments (APAs) determined by trunk muscle activation. Lumbar stabilization exercise programs (LSEP) for patients with LBP may restore the trunk neuromuscular control of the lumbar spine, and normalize APAs. This exploratory study aimed at testing the reliability of EMG and kinematics-based postural adjustment measures over an 8-week interval, assessing their sensitivity to LBP status and treatment and examining their relationship with clinical outcomes. Muscle activation of 10 trunk muscles, using surface electromyography (EMG), and lumbar angular kinematics were recorded during a rapid arm-raising/lowering task. Patients with LBP were tested before and after an 8-week LSEP. Healthy controls receiving no treatment were assessed over the same interval to determine the reliability of the measures and act as a control group at baseline. Muscle activation onsets and reactive range of motion, range of velocities and accelerations were assessed for between group differences at baseline and pre- to post-treatment effects within patients with LBP using t-tests. Correlations between these dependent variables and the change of clinical outcomes (pain, disability) over treatment were also explored. Kinematic-based measures showed comparable reliability to EMG-based measures. Between-group differences were found in lumbar lateral flexion ROM at baseline (patients < controls). In the patients with LBP, lateral flexion velocity and acceleration significantly increased following the LSEP. Correlational analyses revealed that lumbar angular kinematics were more sensitive to changes in pain intensity following the LSEP compared to EMG measures. These findings are interpreted in from the perspective of guarding behaviors and lumbar stability hypotheses. Future clinical trials are needed to target patients with and without delayed APAs at baseline and to explore the sensitivity of different outcome measures related to APAs. Different tasks more challenging to postural stability may need to be explored to more effectively reveal APA dysfunction. Copyright © 2018. Published by Elsevier Ltd.

Central Sensitization and Perceived Indoor Climate among Workers with Chronic Upper-Limb Pain: Cross-Sectional Study

PubMed Central

Jakobsen, Markus D.; Jay, Kenneth; Persson, Roger; Andersen, Lars L.

2015-01-01

Monitoring of indoor climate is an essential part of occupational health and safety. While questionnaires are commonly used for surveillance, not all workers may perceive an identical indoor climate similarly. The aim of this study was to evaluate perceived indoor climate among workers with chronic pain compared with pain-free colleagues and to determine the influence of central sensitization on this perception. Eighty-two male slaughterhouse workers, 49 with upper-limb chronic pain and 33 pain-free controls, replied to a questionnaire with 13 items of indoor climate complaints. Pressure pain threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain-free controls (1.8 [95% CI: 1.3–2.3] versus 0.9 [0.4–1.5], resp.). PPT of the nonpainful leg muscle was negatively associated with the number of complaints. Workers with chronic pain reported more indoor climate complaints than pain-free controls despite similar actual indoor climate. Previous studies that did not account for musculoskeletal pain in questionnaire assessment of indoor climate may be biased. Central sensitization likely explains the present findings. PMID:26425368

Genomic Methods for Clinical and Translational Pain Research

PubMed Central

Wang, Dan; Kim, Hyungsuk; Wang, Xiao-Min; Dionne, Raymond

2012-01-01

Pain is a complex sensory experience for which the molecular mechanisms are yet to be fully elucidated. Individual differences in pain sensitivity are mediated by a complex network of multiple gene polymorphisms, physiological and psychological processes, and environmental factors. Here, we present the methods for applying unbiased molecular-genetic approaches, genome-wide association study (GWAS), and global gene expression analysis, to help better understand the molecular basis of pain sensitivity in humans and variable responses to analgesic drugs. PMID:22351080

Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.

PubMed

Koda, K; Hyakkoku, K; Ogawa, K; Takasu, K; Imai, S; Sakurai, Y; Fujita, M; Ono, H; Yamamoto, M; Fukuda, I; Yamane, S; Morita, A; Asaki, T; Kanemasa, T; Sakaguchi, G; Morioka, Y

2016-07-01

To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis. Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation. Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats. TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The face of pain--a pilot study to validate the measurement of facial pain expression with an improved electromyogram method.

PubMed

Wolf, Karsten; Raedler, Thomas; Henke, Kai; Kiefer, Falk; Mass, Reinhard; Quante, Markus; Wiedemann, Klaus

2005-01-01

The purpose of this pilot study was to establish the validity of an improved facial electromyogram (EMG) method for the measurement of facial pain expression. Darwin defined pain in connection with fear as a simultaneous occurrence of eye staring, brow contraction and teeth chattering. Prkachin was the first to use the video-based Facial Action Coding System to measure facial expressions while using four different types of pain triggers, identifying a group of facial muscles around the eyes. The activity of nine facial muscles in 10 healthy male subjects was analyzed. Pain was induced through a laser system with a randomized sequence of different intensities. Muscle activity was measured with a new, highly sensitive and selective facial EMG. The results indicate two groups of muscles as key for pain expression. These results are in concordance with Darwin's definition. As in Prkachin's findings, one muscle group is assembled around the orbicularis oculi muscle, initiating eye staring. The second group consists of the mentalis and depressor anguli oris muscles, which trigger mouth movements. The results demonstrate the validity of the facial EMG method for measuring facial pain expression. Further studies with psychometric measurements, a larger sample size and a female test group should be conducted.

The neural bases of social pain: Evidence for shared representations with physical pain

PubMed Central

Eisenberger, Naomi I.

2012-01-01

Experiences of social rejection or loss have been described as some of the most ‘painful’ experiences that we, as humans, face and perhaps for good reason. Because of our prolonged period of immaturity, the social attachment system may have co-opted the pain system, borrowing the pain signal to prevent the detrimental consequences of social separation. This review summarizes a program of research that has explored the idea that experiences of physical and social pain rely on shared neural substrates. First, evidence showing that social pain activates pain-related neural regions is reviewed. Then, studies exploring some of the expected consequences of such a physical-social pain overlap are summarized. These studies demonstrate: 1) that individuals who are more sensitive to one kind of pain are also more sensitive to the other and 2) that factors that increase or decrease one kind of pain alter the other in a similar manner. Finally, what these shared neural substrates mean for our understanding of socially painful experience is discussed. PMID:22286852

Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy

PubMed Central

McGreevy, Kai; Bottros, Michael M.; Raja, Srinivasa N.

2011-01-01

Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon. PMID:22102847

Contextual modulation of pain sensitivity utilising virtual environments

PubMed Central

Smith, Ashley; Carlow, Klancy; Biddulph, Tara; Murray, Brooke; Paton, Melissa; Harvie, Daniel S

2017-01-01

Background: Investigating psychological mechanisms that modulate pain, such as those that might be accessed by manipulation of context, is of great interest to researchers seeking to better understand and treat pain. The aim of this study was to better understand the interaction between pain sensitivity, and contexts with inherent emotional and social salience – by exploiting modern immersive virtual reality (VR) technology. Methods: A within-subjects, randomised, double-blinded, repeated measures (RM) design was used. In total, 25 healthy participants were exposed to neutral, pleasant, threatening, socially positive and socially negative contexts, using an Oculus Rift DK2. Pressure pain thresholds (PPTs) were recorded in each context, as well as prior to and following the procedure. We also investigated whether trait anxiety and pain catastrophisation interacted with the relationship between the different contexts and pain. Results: Pressure pain sensitivity was not modulated by context (p = 0.48). Anxiety and pain catastrophisation were not significantly associated with PPTs, nor did they interact with the relationship between context and PPTs. Conclusion: Contrary to our hypothesis, socially and emotionally salient contexts did not influence pain thresholds. In light of other research, we suggest that pain outcomes might only be tenable to manipulation by contextual cues if they specifically manipulate the meaning of the pain-eliciting stimulus, rather than manipulate psychological state generally – as per the current study. Future research might exploit immersive VR technology to better explore the link between noxious stimuli and contexts that directly alter its threat value. PMID:28491299

Bilateral widespread mechanical pain hypersensitivity as sign of central sensitization in patients with cluster headache.

PubMed

Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Cuadrado, María L; López-de-Silanes, Carlos; Pareja, Juan A

2011-03-01

To investigate bilateral widespread pressure pain hyperalgesia in deep tissues over symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with cluster headache (CH). Central sensitization is claimed to play a relevant role in CH. No study has previously searched for widespread pressure hyperalgesia in deep tissues over both symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with CH. Sixteen men (mean age: 43 ± 11 years) with CH in a remission phase and 16 matched controls were recruited. Pressure pain thresholds (PPTs) were bilaterally measured over the supra-orbital (V1), infra-orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves, C5-C6 zygapophyseal joint, mastoid process, and tibialis anterior muscle by an assessor blinded to the subjects' condition. The results showed that PPT levels were significantly decreased bilaterally in patients with CH as compared with healthy controls (all sites, P < .001). A greater degree of sensitization over the mastoid process (P < .001) and a lower degree of sensitization over the tibialis anterior muscle (P < .01) was found. Our findings revealed bilateral widespread pressure pain hypersensitivity in patients with CH confirming the presence of central sensitization mechanisms in this headache condition. © 2010 American Headache Society.

Sciatica: Detection and Confirmation by New Method

PubMed Central

Nadkarni, Sunil

2014-01-01

We need to overcome limitations of present assessment and also integrate newer research in our work about sciatica. Inflammation induces changes in the DRG and nerve root. It sensitizes the axons. Nociceptor is a unique axon. It is pseudo unipolar: both its ends, central and peripheral, behave in similar fashion. The nerve in periphery which carries these axons may selectively become sensitive to mechanical pressure--“mechanosensitized,” as we coin the phrase. Many pain questionnaires are used and are effective in identifying neuropathic pain solely on basis of descriptors but they do not directly physically correlate nerve root and pain. A thorough neurological evaluation is always needed. Physical examination is not direct pain assessment but testing mobility of nerve root and its effect on pain generation. There is a dogmatic dominance of dermatomes in assessment of leg pain. They are unreliable. Images may not correlate with symptoms and pathology in about 28% of cases. Electrophysiology may be normal in purely inflamed nerve root. Palpation may help in such inflammatory setting to refine our assessment further. Confirmation of sciatica is done by selective nerve root block (SNRB) today but it is fraught with several complications and needs elaborate inpatient and operating room set up. We have used the unique property of the pseudo unipolar axon that both its ends have similar functional properties and so inject along its peripheral end sodium channel blockers to block the basic cause of the mechanosensitization namely upregulated sodium channels in the root or DRG. Thus using palpation we may be able to detect symptomatic nerve in stage of inflammation and with distal end injection, along same inflamed nerve we may be able to abolish and so confirm sciatica. Discussions of sciatica pain diagnosis tend to immediately shift and centre on the affected disc rather than the nerve. Theoretically it may be possible to detect the affected nerve by palpating the nerve and relieve pain moment we desensitize the nerve. PMID:25694916

Altered pain sensitivity and axioscapular muscle activity in neck pain patients compared with healthy controls.

PubMed

Christensen, S W; Hirata, R P; Graven-Nielsen, T

2017-11-01

Previous studies have indicated that neck pain patients feel increased symptoms following upper limb activities, and altered axioscapular muscle function has been proposed as a contributing factor. Pain sensitivity and muscle activity, during arm movements, were assessed in neck pain patients and controls. Patients with ongoing insidious-onset neck pain (IONP, N = 16) and whiplash-associated disorders (WAD, N = 9) were included along with sex- and age-matched controls (N = 25). Six series of repeated arm abductions were performed during electromyographic (EMG) recordings from eight bilateral muscles. The first and last three series were separated by 8 min and 42 s, respectively. Each series consisted of three slow and three fast movements. Pressure pain thresholds (PPTs) were recorded bilaterally from neck, head and arm at baseline, after the third and sixth movement series. Pain intensity was recorded on an electronic visual analogue scale (VAS). Larger pain areas and higher VAS scores were found in patients compared with controls (p < 0.001), and in patients, the VAS scores increased in the course of movements (p < 0.02). PPTs were lower in patients compared with controls at all sites (p < 0.03), and these decreased during arm movements in the IONP group (p < 0.03), while increasing at head and neck sites in controls (p < 0.04). During the slow movements, increasing serratus anterior EMG activity was found in the series with short breaks in-between for the WAD group compared with IONP and controls (p < 0.001). Axioscapular movement caused different responses in pain sensitivity and muscle activity between neck pain patient groups compared with controls. Neck pain patients report increased symptoms following upper limb activities. This study shows that repeated arm movements caused differentiated responses in pain sensitivity and muscle activity between subgroups of neck pain patient and asymptomatic controls. Such findings may be of great clinical significance when planning rehabilitation for this patient population. © 2017 European Pain Federation - EFIC®.