Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: comorbid pain matters.

PubMed

Johansen, Aslak; Schirmer, Henrik; Stubhaug, Audun; Nielsen, Christopher S

2014-02-01

In a large survey incorporating medical examination (N=12,981), information on chronic pain and surgery was collected, and sensitivity to different pain modalities was tested. Tolerance to the cold pressor test was analysed with survival statistics for 10,486 individuals, perceived cold pressor pain intensity was calculated for 10,367 individuals, heat pain threshold was assessed for 4,054 individuals, and pressure pain sensitivity for 4,689 individuals. Persistent post-surgical pain, defined by self-report, was associated with lower cold pressor tolerance (sex-adjusted hazard ratio=1.34, 95% confidence interval=1.08-1.66), but not when adjusting for other chronic pain. Other experimental pain modalities did not differentiate between individuals with or without post-surgical pain. Of the individuals with chronic pain (N=3352), 6.2% indicated surgery as a cause, although only 0.5% indicated surgery as the only cause. The associations found between persistent post-surgical pain and cold pressor tolerance is largely explained by the co-existence of chronic pain from other causes. We conclude that most cases of persistent post-surgical pain are coexistent with other chronic pain, and that, in an unselected post-surgical population, persistent post-surgical pain is not significantly associated with pain sensitivity when controlling for comorbid pain from other causes. A low prevalence of self-reported persistent pain from surgery attenuates statistically significant associations. We hypothesize that general chronic pain is associated with central changes in pain processing as expressed by reduced tolerance for the cold pressor test. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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.

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.

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.

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

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.

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.

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

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

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.

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

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

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.

Bilateral experimental neck pain reorganize axioscapular muscle coordination and pain sensitivity.

PubMed

Christensen, S W; Hirata, R P; Graven-Nielsen, T

2017-04-01

Neck pain is a large clinical problem where reorganized trunk and axioscapular muscle activities have been hypothesised contributing to pain persistence and pain hypersensitivity. This study investigated the effects of bilateral experimental neck pain on trunk and axioscapular muscle function and pain sensitivity. In 25 healthy volunteers, bilateral experimental neck pain was induced in the splenius capitis muscles by hypertonic saline injections. Isotonic saline was used as control. In sitting, subjects performed slow, fast and slow-resisted unilateral arm movements before, during and after injections. Electromyography (EMG) was recorded from eight shoulder and trunk muscles bilaterally. Pressure pain thresholds (PPTs) were assessed bilaterally at the neck, head and arm. Data were normalized to the before-measures. Compared with control and post measurements, experimental neck pain caused (1) decreased EMG activity of the ipsilateral upper trapezius muscles during all but slow-resisted down movements (p < 0.001), and (2) increased EMG activity in the ipsilateral erector spinae muscle during slow and fast movements (p < 0.02), and in the contralateral erector spinae muscle during all but fast up and slow-resisted down movements (p < 0.007). The PPTs in the painful condition increased at the head and arm compared with post measurements and the control condition (p < 0.001). In the post-pain condition, the neck PPT was decreased compared with the control condition (p < 0.001). Acute bilateral neck pain reorganized axioscapular and trunk muscle activity together with local hyperalgesia and widespread hypoalgesia indicating that acute neck pain immediately affects trunk and axioscapular function which may affect both assessment and treatment. Bilateral clinical neck pain alters axioscapular muscle coordination but only effects of unilateral experimental neck pain has been investigated. Bilateral experimental neck pain causes task-dependent reorganized

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

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

Postinflammatory visceral sensitivity and pain mechanisms.

PubMed

Vergnolle, N

2008-05-01

The inflammatory reaction is normally tightly regulated, and as soon as the original insult has been cleared, a resolution phase starts that aims at leading the tissues back to a normal physiological state. However, after intestinal inflammation, a number of patients develop postinflammatory hypersensitivity symptoms, which can be defined as an excessive sensitivity to gut nociceptive stimulation. The pain experienced by those patients has been largely studied in the context of postinfectious intestinal diseases. The mechanisms of postinflammatory persistent visceral pain involve peripheral and central neuroplastic changes, low-grade chronic inflammation that sensitizes visceral afferent pathways and sensitization of non-neuronal resident cells of the gut. Several molecular determinants such as neurokinins, serotonin, proteases and voltage-gated ion channels seem to play a significant role in the control of postinflammatory visceral sensation. This review tries to give insights into the mechanisms of persistent visceral pain following the resolution of intestinal inflammation and tries to identify what needs to be done to further advance the field of postinflammatory hypersensitivity clinical management.

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.

Modification of COMT-dependent pain sensitivity by psychological stress and sex.

PubMed

Meloto, Carolina B; Bortsov, Andrey V; Bair, Eric; Helgeson, Erika; Ostrom, Cara; Smith, Shad B; Dubner, Ronald; Slade, Gary D; Fillingim, Roger B; Greenspan, Joel D; Ohrbach, Richard; Maixner, William; McLean, Samuel A; Diatchenko, Luda

2016-04-01

Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity.

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

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.

Integrative Approach to Pain Genetics Identifies Pain Sensitivity Loci across Diseases

PubMed Central

Ruau, David; Dudley, Joel T.; Chen, Rong; Phillips, Nicholas G.; Swan, Gary E.; Lazzeroni, Laura C.; Clark, J. David

2012-01-01

Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI), derived from Medical Subject Heading (MESH) annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10−10) for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10−4, 1.8×10−4, and 2.2×10−4 respectively). Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates. PMID:22685391

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.

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.

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

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

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.

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.

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.

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 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.

No effects of hydrocortisone and dexamethasone on pain sensitivity in healthy individuals.

PubMed

Wingenfeld, K; Wolf, S; Kunz, M; Krieg, J-C; Lautenbacher, S

2015-07-01

There is some evidence that stress-induced cortisol increase leads to a decrease in pain, while lowering cortisol levels enhances pain sensitivity, but no study has yet investigated both pharmacological enhancement and reduction of cortisol levels in the same individuals. Firstly, we tested in 16 healthy individuals whether the treatment with hydrocortisone and dexamethasone, respectively, results in altered pain thresholds. Secondly, we aimed to test whether hormone effects are different across the pain range by using ratings for pain stimuli with varying intensity; and thirdly, we tested whether cortisol levels influence the discrimination ability for painful stimuli. Despite substantial effects of dexamethasone and hydrocortisone administration on cortisol levels, no effect of these drugs was seen in terms of pain sensitivity (pain threshold, pain rating, pain discrimination ability), although comprehensively examined. However, in the placebo condition, a significant negative correlation between cortisol and pain thresholds was seen. Similarly, there were also strong negative associations between cortisol levels in the placebo condition and pain thresholds after drug treatment (especially after hydrocortisone). These findings suggest that short-term variations of cortisol do not influence pain sensitivity whereas, in general, high levels of cortisol are associated with increased pain sensitivity, at least for weak to moderate stimuli. © 2014 European Pain Federation - EFIC®

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.

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.

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

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

Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome.

PubMed

Jarrett, M E; Han, C J; Cain, K C; Burr, R L; Shulman, R J; Barney, P G; Naliboff, B D; Zia, J; Heitkemper, M M

2016-07-01

Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test. As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS-diarrhea [IBS-D], IBS-constipation plus mixed [IBS-CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS-CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS-CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. Despite similar levels of abdominal pain in IBS, the IBS-CM group demonstrated greater sensitivity to both thermal and visceral testing procedures. © 2016 John Wiley & Sons Ltd.

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

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®

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

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.

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.

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

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

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

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.

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

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 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

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.

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.

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

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

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

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.

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.

Pain sensitivity: an unnatural history from 1800 to 1965.

PubMed

Bourke, Joanna

2014-09-01

Who was truly capable of experiencing pain? In this article, I explore ideas about the distribution of bodily sensitivity in patients from the early nineteenth century to 1965 in Anglo-American societies. While certain patients were regarded as "truly hurting," other patients' distress could be disparaged or not even registered as being "real pain." Such judgments had major effects on regimes of pain-alleviation. Indeed, it took until the late twentieth century for the routine underestimation of the sufferings of certain groups of people to be deemed scandalous. Often the categorizations were contradictory. For instance, the humble status of workers and immigrants meant that they were said to be insensitive to noxious stimuli; the profound inferiority of these same patients meant that they were especially likely to respond with "exaggerated" sensitivity. How did physicians hold such positions simultaneously? Pain-assignation claimed to be based on natural hierarchical schemas, but the great Chain of Feeling was more fluid than it seemed.

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

Pleasure and pain: the effect of (almost) having an orgasm on genital and nongenital sensitivity.

PubMed

Paterson, Laurel Q P; Amsel, Rhonda; Binik, Yitzchak M

2013-06-01

The effect of sexual arousal and orgasm on genital sensitivity has received little research attention, and no study has assessed sensation pleasurableness as well as painfulness. To clarify the relationship between sexual arousal, orgasm, and sensitivity in a healthy female sample. Twenty-six women privately masturbated to orgasm and almost to orgasm at two separate sessions, during which standardized pressure stimulation was applied to the glans clitoris, vulvar vestibule, and volar forearm at three testing times: (i) baseline; (ii) immediately following masturbation; and (iii) following a subsequent 15-minute rest period. Touch thresholds (tactile detection sensitivity), sensation pleasurableness ratings (pleasurable sensitivity), and pain thresholds (pain sensitivity). Pleasurableness ratings were higher on the glans clitoris than the vulvar vestibule, and at most testing times on the vulvar vestibule than the volar forearm; and at baseline and immediately after masturbation than 15 minutes later, mainly on the genital locations only. Pain thresholds were lower on the genital locations than the volar forearm, and immediately and 15 minutes after masturbation than at baseline. After orgasm, genital pleasurableness ratings and vulvar vestibular pain thresholds were lower than after masturbation almost to orgasm. Post-masturbation pleasurableness ratings were positively correlated with pain thresholds but only on the glans clitoris. Hormonal contraception users had lower pleasurableness ratings and pain thresholds on all locations than nonusers. There were no significant effects for touch thresholds. Masturbation appears to maintain pleasurable genital sensitivity but increase pain sensitivity, with lower genital pleasurable sensitivity and higher vulvar vestibular pain sensitivity when orgasm occurs. Findings suggest that enhancing stimulation pleasurableness, psychological sexual arousal and lubrication mitigate normative increases in pain sensitivity during

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.

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.

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

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.

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.

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

Anxiety sensitivity, body vigilance and fear of pain.

PubMed

Esteve, M Rosa; Camacho, Laura

2008-06-01

The aim of the present study was to investigate the role of anxiety sensitivity (AS) as a factor relevant to pain and pain persistence. Two studies were conducted to examine the relationship between AS, body vigilance and the experience of pain in non-clinical samples. Study 1 investigated the relationship between AS and body vigilance that was operationalized by the detection latency for innocuous electrical stimuli; trait anxiety and neuroticism were also included as covariates. Results indicated that the high AS group (N=69) presented shorter detection latency than the low AS group (N=70); neuroticism and trait anxiety did not have significant effects on detection latency. Using another sample, Study 2 investigated the relationship between AS, body vigilance, pain tolerance, catastrophizing, and self-reported distress and pain during a cold pressor task. Neuroticism, trait anxiety and fear of pain were included as covariates. Results showed significant differences between high- (N=66) and low- (N=69) AS groups in body vigilance, catastrophizing and tolerance. The covariates neuroticism, trait anxiety and fear of pain did not have any significant effects. No significant differences were found in pain and distress ratings. Results from both studies support the importance of AS in body vigilance and the experience of pain. The theoretical, preventive and clinical implications of these findings are discussed.

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

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.

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.

Positive and negative affect dimensions in chronic knee osteoarthritis: effects on clinical and laboratory pain.

PubMed

Finan, Patrick H; Quartana, Phillip J; Smith, Michael T

2013-06-01

This study investigated whether daily and laboratory assessed pain differs as a function of the temporal stability and valence of affect in individuals with chronic knee osteoarthritis (KOA). One hundred fifty-one men and women with KOA completed 14 days of electronic diaries assessing positive affect (PA), negative affect (NA), and clinical pain. A subset of participants (n =79) engaged in quantitative sensory testing (QST). State PA and NA were assessed prior to administration of stimuli that induced suprathreshold pain and temporal summation. Multilevel modeling and multiple regression evaluated associations of affect and pain as a function of valence (i.e., positive versus negative) and stability (i.e., stable versus state). In the diary, stable NA (B = -.63, standard error [SE] = .13, p < .001) was a stronger predictor of clinical KOA pain than stable PA (B = -.18, SE = .11, p = .091), and state PA (B = -.09, p < .001) was a stronger predictor of concurrent daily clinical pain than state NA (B = .04, SE = .02, p = .068). In the laboratory, state PA (B = -.05, SE = .02, p = .042), but not state NA (p = .46), predicted diminished temporal summation of mechanical pain. Stable NA is more predictive of clinical pain than stable PA, whereas state PA is more predictive of both clinical and laboratory pain than state NA. The findings suggest that dynamic affect-pain processes in the field may reflect individual differences in central pain facilitation.

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

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

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.

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

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

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

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 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.

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.

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

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

Oxidation Sensitive Nociception Involved in Endometriosis Associated Pain

PubMed Central

Ray, Kristeena; Fahrmann, Johannes; Mitchell, Brenda; Paul, Dennis; King, Holly; Crain, Courtney; Cook, Carla; Golovko, Mikhail; Brose, Stephen; Golovko, Svetlana; Santanam, Nalini

2015-01-01

Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu, rich in inflammatory markers and pain-inducing prostaglandins PGE2/PGF2α and lipid peroxides, and the endometriotic tissue is innervated with nociceptors. Our clinical study showed the abundance of oxidatively-modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively-modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (i) the detection of lipoprotein derived oxidation-sensitive pain molecules, (ii) the ability of such molecules to induce nociception, and (iii) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins similar to that seen in the PF. The oxidatively-modified lipoproteins induced hypothermia (intra-cerebroventricular) in CD-1 mice and nociception in the Hargreaves paw-withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin-E and N-acetylcysteine and the NSAID, indomethacin suppressed the pain inducing ability of oxidatively-modified lipoproteins. Treatment of human endometrial cells with oxidatively-modified lipoproteins or PF from women with endometriosis showed up-regulation of similar genes belonging to the opioid and inflammatory pathways. Our finding that oxidatively-modified lipoproteins can induce nociception has a broader impact not only in the treatment of endometriosis-associated pain but also in other diseases associated with chronic pain. PMID:25599233

Pulp Sensitivity: Influence of Sex, Psychosocial Variables, COMT Gene, and Chronic Facial Pain.

PubMed

Mladenovic, Irena; Krunic, Jelena; Supic, Gordana; Kozomara, Ruzica; Bokonjic, Dejan; Stojanovic, Nikola; Magic, Zvonko

2018-05-01

The purpose of this study was to evaluate the associations of variability in pulp sensitivity with sex, psychosocial variables, the gene that encodes for the enzyme catechol-O-methyltransferase (COMT), and chronic painful conditions (temporomandibular disorders [TMDs]). The study was composed of 97 subjects (68 women and 29 men aged 20-44 years). The electric (electric pulp tester) and cold (refrigerant spray) stimuli were performed on mandibular lateral incisors. The results were expressed as pain threshold values for electric pulp stimulation (0-80 units) and as pain intensity scores (visual numeric scale from 0-10) for cold stimulation. The Research Diagnostic Criteria for TMD were used to assess TMD, depression, and somatization. DNA extracted from peripheral blood was genotyped for 3 COMT polymorphisms (rs4680, rs6269, and rs165774) using the real-time TaqMan method. Multivariate linear regression was used to investigate the joint effect of the predictor variables (clinical and genetic) on pulp sensitivity (dependent variables). Threshold responses to electric stimuli were related to female sex (P < .01) and the homozygous GG genotype for the rs165774 polymorphism (P < .05). Pain intensity to cold stimuli was higher in TMD patients (P < .01) and tended to be higher in women. Multivariate linear regression identified sex and the rs165774 COMT polymorphism as the determinants of electric pain sensitivity, whereas TMD accounts for the variability in the cold response. Our findings indicate that sex/a COMT gene variant and TMD as a chronic painful condition may contribute to individual variation in electric and cold pulp sensitivity, respectively. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Sex, gender, and age: contributions to laboratory pain responding in children and adolescents.

PubMed

Myers, Cynthia D; Tsao, Jennie C I; Glover, Dorie A; Kim, Su C; Turk, Norman; Zeltzer, Lonnie K

2006-08-01

A cross-sectional design across late childhood and adolescence examined the influence of sex, gender socialization, and age on responses to controlled laboratory pain tasks. Healthy children and adolescents (n = 240, 50% female, age 8 to 18 years) completed the Child Sex Role Inventory, a self-report measure of identification with stereotypically masculine and feminine personality traits, as an index of gender socialization and participated in pressure, cold pressor, and heat pain tasks. Pain tolerance, pain intensity, and bothersomeness of each pain task were assessed. Masculinity correlated with lower heat pain ratings in boys but not girls. Logistic regression indicated cold pain intensity ratings were predicted by sex, gender score, and the age-by-gender score interaction. Heat pain intensity was predicted by age, gender score, age-by-gender score interaction, and sex-by-gender score. The current findings support closer examination of the influence of gender socialization on young people's pain responses and highlight the importance of a multifactorial, developmental approach to studying the impact of gender socialization on the emergence of sex differences in pain responses after puberty.

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.

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.

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

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.

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

Generalized mechanical pain sensitivity over nerve tissues in patients with strictly unilateral migraine.

PubMed

Fernández-de-las-Peñas, César; Arendt-Nielsen, Lars; Cuadrado, María Luz; Pareja, Juan A

2009-06-01

No study has previously analyzed pressure pain sensitivity of nerve trunks in migraine. This study aimed to examine the differences in mechanical pain sensitivity over specific nerves between patients with unilateral migraine and healthy controls. Blinded investigators assessed pressure pain thresholds (PPT) over the supra-orbital nerves (V1) and peripheral nerve trunks of both upper extremities (median, radial, and ulnar nerves) in 20 patients with strictly unilateral migraine and 20 healthy matched controls. Pain intensity after palpation over both supra-orbital nerves was also assessed. A pressure algometer was used to quantify PPT, whereas a 10-point numerical pain rate scale was used to evaluate pain to palpation over the supra-orbital nerve. The analysis of covariance revealed that pain to palpation over the supra-orbital nerve was significantly higher (P<0.001) on the symptomatic side (mean: 3.4, SD: 1.5) as compared with the nonsymptomatic side (mean: 0.5, SD: 1.2) in patients with migraine and both the dominant (mean: 0.2, SD: 0.4) and nondominant (mean: 0.3, SD: 0.5) sides in healthy controls. PPT assessed over the supra-orbital nerve on the symptomatic side (mean: 1.05, SD: 0.2 kg/cm) was significantly lower (P<0.05) than PPT measurements on the nonsymptomatic side (mean: 1.35, SD: 0.3 kg/cm) and either the dominant (mean: 1.9, SD: 0.2 kg/cm) or nondominant (mean: 1.9, SD: 0.3 kg/cm) sides in controls (P<0.001). Finally, PPT assessed over the median, ulnar, and radial nerves were significantly lower in patients with migraine as compared with controls (P<0.001), without side-to-side differences (P>0.6). In patients with unilateral migraine, we found increased mechano-sensitivity of the supra-orbital nerve on the symptomatic side of the head. Outside the head, the same patients showed increased mechano-sensitivity of the main peripheral nerves of both upper limbs, without asymmetries. Such diffuse hypersensitivity of the peripheral nerves lends further

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.

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.

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

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.

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.

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

The Consequence of Combined Pain and Stress on Work Ability in Female Laboratory Technicians: A Cross-Sectional Study.

PubMed

Jay, Kenneth; Friborg, Maria Kristine; Sjøgaard, Gisela; Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel; Andersen, Lars Louis

2015-12-11

Musculoskeletal pain and stress-related disorders are leading causes of impaired work ability, sickness absences and disability pensions. However, knowledge about the combined detrimental effect of pain and stress on work ability is lacking. This study investigates the association between pain in the neck-shoulders, perceived stress, and work ability. In a cross-sectional survey at a large pharmaceutical company in Denmark 473 female laboratory technicians replied to questions about stress (Perceived Stress Scale), musculoskeletal pain intensity (scale 0-10) of the neck and shoulders, and work ability (Work Ability Index). General linear models tested the association between variables. In the multi-adjusted model, stress (p < 0.001) and pain (p < 0.001) had independent main effects on the work ability index score, and there was no significant stress by pain interaction (p = 0.32). Work ability decreased gradually with both increased stress and pain. Workers with low stress and low pain had the highest Work Ability Index score (44.6 (95% CI 43.9-45.3)) and workers with high stress and high pain had the lowest score (32.7 (95% CI 30.6-34.9)). This cross-sectional study indicates that increased stress and musculoskeletal pain are independently associated with lower work ability in female laboratory technicians.

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

Laboratory environmental factors and pain behavior: the relevance of unknown unknowns to reproducibility and translation.

PubMed

Mogil, Jeffrey S

2017-03-22

The poor record of basic-to-clinical translation in recent decades has led to speculation that preclinical research is "irreproducible", and this irreproducibility in turn has largely been attributed to deficiencies in reporting and statistical practices. There are, however, a number of other reasonable explanations of both poor translation and difficulties in one laboratory replicating the results of another. This article examines these explanations as they pertain to preclinical pain research. I submit that many instances of apparent irreproducibility are actually attributable to interactions between the phenomena and interventions under study and "latent" environmental factors affecting the rodent subjects. These environmental variables-often causing stress, and related to both animal husbandry and the specific testing context-differ greatly between labs, and continue to be identified, suggesting that our knowledge of their existence is far from complete. In pain research in particular, laboratory stressors can produce great variability of unpredictable direction, as stress is known to produce increases (stress-induced hyperalgesia) or decreases (stress-induced analgesia) in pain depending on its parameters. Much greater attention needs to be paid to the study of the laboratory environment if replication and translation are to be improved.

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.

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

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.

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.

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.

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.

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.

Transferability and within- and between-laboratory reproducibilities of EpiSensA for predicting skin sensitization potential in vitro: A ring study in three laboratories.

PubMed

Mizumachi, Hideyuki; Sakuma, Megumi; Ikezumi, Mayu; Saito, Kazutoshi; Takeyoshi, Midori; Imai, Noriyasu; Okutomi, Hiroko; Umetsu, Asami; Motohashi, Hiroko; Watanabe, Mika; Miyazawa, Masaaki

2018-05-03

The epidermal sensitization assay (EpiSensA) is an in vitro skin sensitization test method based on gene expression of four markers related to the induction of skin sensitization; the assay uses commercially available reconstructed human epidermis. EpiSensA has exhibited an accuracy of 90% for 72 chemicals, including lipophilic chemicals and pre-/pro-haptens, when compared with the results of the murine local lymph node assay. In this work, a ring study was performed by one lead and two naive laboratories to evaluate the transferability, as well as within- and between-laboratory reproducibilities, of EpiSensA. Three non-coded chemicals (two lipophilic sensitizers and one non-sensitizer) were tested for the assessment of transferability and 10 coded chemicals (seven sensitizers and three non-sensitizers, including four lipophilic chemicals) were tested for the assessment of reproducibility. In the transferability phase, the non-coded chemicals (two sensitizers and one non-sensitizer) were correctly classified at the two naive laboratories, indicating that the EpiSensA protocol was transferred successfully. For the within-laboratory reproducibility, the data generated with three coded chemicals tested in three independent experiments in each laboratory gave consistent predictions within laboratories. For the between-laboratory reproducibility, 9 of the 10 coded chemicals tested once in each laboratory provided consistent predictions among the three laboratories. These results suggested that EpiSensA has good transferability, as well as within- and between-laboratory reproducibility. Copyright © 2018 John Wiley & Sons, Ltd.

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®

Dissatisfaction with own body makes patients with eating disorders more sensitive to pain

PubMed Central

Yamamotova, Anna; Bulant, Josef; Bocek, Vaclav; Papezova, Hana

2017-01-01

Body image represents a multidimensional concept including body image evaluation and perception of body appearance. Disturbances of body image perception are considered to be one of the central aspects of anorexia nervosa and bulimia nervosa. There is growing evidence that body image distortion can be associated with changes in pain perception. The aim of our study was to examine the associations between body image perception, body dissatisfaction, and nociception in women with eating disorders and age-matched healthy control women. We measured body dissatisfaction and pain sensitivity in 61 patients with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnoses of eating disorders (31 anorexia nervosa and 30 bulimia nervosa) and in 30 healthy women. Thermal pain threshold latencies were evaluated using an analgesia meter and body image perception and body dissatisfaction were assessed using Anamorphic Micro software (digital pictures of their own body distorted into larger-body and thinner-body images). Patients with eating disorders overestimated their body size in comparison with healthy controls, but the two groups did not differ in body dissatisfaction. In anorexia and bulimia patient groups, body dissatisfaction (calculated in pixels as desired size/true image size) correlated with pain threshold latencies (r=0.55, p=0.001), while between body image perception (determined as estimation size/true image size) and pain threshold, no correlation was found. Thus, we demonstrated that in patients with eating disorders, pain perception is significantly associated with emotional contrary to sensory (visual) processing of one’s own body image. The more the patients desired to be thin, the more pain-sensitive they were. Our findings based on some shared mechanisms of body dissatisfaction and pain perception support the significance of negative emotions specific for eating disorders and contribute to better understanding of the psychosomatic

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.

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.

Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome: evidence of central processing in unilateral neuropathy.

PubMed

Fernández-de-las-Peñas, César; de la Llave-Rincón, Ana Isabel; Fernández-Carnero, Josué; Cuadrado, María Luz; Arendt-Nielsen, Lars; Pareja, Juan A

2009-06-01

The aim of this study was to investigate whether bilateral widespread pressure hypersensitivity exists in patients with unilateral carpal tunnel syndrome. A total of 20 females with carpal tunnel syndrome (aged 22-60 years), and 20 healthy matched females (aged 21-60 years old) were recruited. Pressure pain thresholds were assessed bilaterally over median, ulnar, and radial nerve trunks, the C5-C6 zygapophyseal joint, the carpal tunnel and the tibialis anterior muscle in a blinded design. The results showed that pressure pain threshold levels were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, the C5-C6 zygapophyseal joint, and the tibialis anterior muscle in patients with unilateral carpal tunnel syndrome as compared to healthy controls (all, P < 0.001). Pressure pain threshold was negatively correlated to both hand pain intensity and duration of symptoms (all, P < 0.001). Our findings revealed bilateral widespread pressure hypersensitivity in subjects with carpal tunnel syndrome, which suggest that widespread central sensitization is involved in patients with unilateral carpal tunnel syndrome. The generalized decrease in pressure pain thresholds associated with pain intensity and duration of symptoms supports a role of the peripheral drive to initiate and maintain central sensitization. Nevertheless, both central and peripheral sensitization mechanisms are probably involved at the same time in carpal tunnel syndrome.

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

Central sensitization and neuropathic features of ongoing pain in a rat model of advanced osteoarthritis

PubMed Central

Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

2015-01-01

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 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 while a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present studies, palpation of the ipsilateral hindlimb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced FOS expression in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways by microinjection of lidocaine within the rostral ventromedial medulla (RVM) induced conditioned place preference (CPP) selectively in rats treated with the high dose of MIA. CPP to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, i.p. at −30 min). 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 may guide drug discovery for treatment of advanced OA pain without the need for joint replacement. PMID:26694132

Ecological aspects of pain in sensory modulation disorder.

PubMed

Bar-Shalita, T; Deutsch, L; Honigman, L; Weissman-Fogel, I

2015-01-01

Sensory Modulation Disorder (SMD) interferes with the daily life participation of otherwise healthy individuals and is characterized by over-, under- or seeking responsiveness to naturally occurring sensory stimuli. Previous laboratory findings indicate pain hyper-sensitivity in SMD individuals suggesting CNS alteration in pain processing and modulation. However, laboratory studies lack ecological validity, and warrant clinical completion in order to elicit a sound understanding of the phenomenon studied. Thus, this study explored the association between sensory modulation and pain in a daily life context in a general population sample. Daily life context of pain and sensations were measured in 250 adults (aged 23-40 years; 49.6% males) using 4 self-report questionnaires: Pain Sensitivity Questionnaire (PSQ) and Pain Catastrophizing Scale (PCS) to evaluate the sensory and cognitive aspects of pain; the Sensory Responsiveness Questionnaire (SRQ) to appraise SMD; and the Short Form - 36 Health Survey, version 2 (SF36) to assess health related Quality of Life (QoL). Thirty two individuals (12.8%) were found with over-responsiveness type of SMD, forming the SOR-SMD group. While no group differences (SOR-SMD vs. Non-SMD) were found, low-to-moderate total sample correlations were demonstrated between the SRQ-Aversive sub-scale and i) PSQ total (r=0.31, p<0.01) and sub-scales scores (r=0.27-0.28, p<0.01), as well as ii) PCS total and the sub-scales of Rumination and Helplessness scores (r=0.15, p<0.05). PSQ total and sub-scale scores were more highly correlated with SRQ-Aversive in the SOR-SMD group (r=0.57-0.68, p=0.03-<0.01) compared to Non-SMD group. The Physical Health - Total score (but not the Mental Health - Total) of the SF36 was lower for the SOR-SMD group (p=0.03), mainly due to the difference in the Body pain sub-scale (p=0.04). Results suggest that SOR-SMD is strongly associated with the sensory aspect of pain but weakly associated with the cognitive aspect

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.

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

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

Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity.

PubMed

Vaegter, Henrik B; Graven-Nielsen, Thomas

2016-07-01

Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). Heat detection and heat pain thresholds at clinical painful and nonpainful body areas were assessed. Based on TSP and CPM, 4 distinct groups were formed: group 1 (n = 85) had impaired CPM and facilitated TSP; group 2 (n = 148) had impaired CPM and normal TSP; group 3 (n = 45) had normal CPM and facilitated TSP; and group 4 (n = 122) had normal CPM and normal TSP. Group 1 showed more pain regions than the other 3 groups (P < 0.001), indicating that impaired CPM and facilitated TSP play an important role in widespread pain. Groups 1 and 2 compared with group 4 had lower heat pain threshold at nonpainful areas and lower cuff pressure pain tolerance (P < 0.02), indicating that CPM plays a role for widespread hyperalgesia. Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.

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

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

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.

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.

Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions

PubMed Central

Pezet, Sophie; Marchand, Fabien; D'Mello, Richard; Grist, John; Clark, Anna K.; Malcangio, Marzia; Dickenson, Anthony H.; Williams, Robert J.; McMahon, Stephen B.

2010-01-01

Here we show that phosphatidylinositol 3-kinase (PI3K) is a key player in the establishment of central sensitization, the spinal cord phenomenon associated with persistent afferent inputs and contributing to chronic pain states. We demonstrated electrophysiologically that PI3K is required for the full expression of spinal neuronal wind-up. In an inflammatory pain model, intrathecal administration of LY294002, a potent PI3K inhibitor, dose-dependently inhibited pain related behavior. This effect was correlated with a reduction of the phosphorylation of extracellular signal-regulated kinase (ERK) and CaMKinase II. In addition, we observed a significant decrease in the phosphorylation of the NMDA receptor subunit NR2B, decreased translocation to the plasma membrane of the GluR1 AMPA receptor subunit in the spinal cord and a reduction of evoked neuronal activity as measured using c-Fos immunohistochemistry. Our study suggests that PI3K is a major factor in the expression of central sensitization after noxious inflammatory stimuli. PMID:18417706

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.

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.

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain

PubMed Central

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R.; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-01-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, TNF-α transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose-dependently inhibited by the JNK inhibitors SP600125 and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Further, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous excitatory synaptic currents (sEPSCs) but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Taken together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes following JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. PMID:19339605

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

PubMed

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-04-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

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.

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.

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

Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain.

PubMed

Yunus, Muhammad B

2007-06-01

Patients with widespread pain or fibromyalgia syndrome have many symptoms besides musculoskeletal pain: e.g. fatigue, sleep difficulties, a swollen feeling in tissues, paresthesia, cognitive dysfunction, dizziness, and symptoms of overlapping conditions such as irritable bowel syndrome, headaches and restless legs syndrome. There is evidence for central sensitization in these conditions, but further studies are needed. Anxiety, stress and depression are also present in 30-45% of patients. Other factors that may contribute to symptoms include endocrine dysfunction, psychosocial distress, trauma, and disrupted sleep. Evaluation of a patient presenting with widespread pain includes history and physical examination to diagnose both fibromyalgia and associated or concomitant conditions. Fibromyalgia should be diagnosed by its own characteristic features. Some patients with otherwise typical symptoms of fibromyalgia may have as few as four to six tender points in clinical practice. Patients with rheumatoid arthritis and systemic lupus erythematosus should be evaluated for fibromyalgia, since 20-30% of them have associated fibromyalgia, requiring a different treatment approach.

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.

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

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

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

Pain assessment and management in patients undergoing endovascular procedures in the catheterization laboratory.

PubMed

Hilário, Thamires de Souza; Santos, Simone Marques Dos; Kruger, Juliana; Goes, Martha Georgina; Casco, Márcia Flores; Rabelo-Silva, Eneida Rejane

2017-05-25

To describe how pain is assessed (characteristic, location, and intensity) and managed in clinical practice in patients undergoing endovascular procedures in the catheterization laboratory setting. Cross-sectional study with retrospective data collection. Overall, 345 patients were included; 116 (34%) experienced post-procedural pain; in 107 (92%), pain characteristics were not recorded; the location of pain was reported in 100% of patients, and its intensity in 111 (96%); management was largely pharmacologic; of the patients who received some type of management (n=71), 42 (59%) underwent reassessment of pain. The location and intensity of pain are well reported in clinical practice. Pharmacologic pain management is still prevalent. Additional efforts are needed to ensure recording of the characteristics of pain and its reassessment after interventions. Describir cómo se evalúa el dolor (características, localización e intensidad) y su manejo en la práctica clínica en pacientes sometidos a procedimientos endovasculares en el laboratorio de cateterización. Estudio transversal con recolección retrospectiva de datos. En total, se incluyeron 345 pacientes; 116 (34%) experimentaron dolor post-procedimiento; en 107 (92%), no se registraron las características del dolor; la localización del dolor se informó en el 100% de los pacientes, y su intensidad en 111 (96%); el manejo fue en gran medida farmacológico; de los pacientes que recibieron algún tipo de tratamiento (n=71), 42 (59%) fueron sometidos a reevaluación del dolor. La ubicación y la intensidad del dolor se informan bien en la práctica clínica. El manejo farmacológico del dolor sigue siendo frecuente. Se necesitan esfuerzos adicionales para asegurar el registro de las características del dolor y su reevaluación después de las intervenciones.

Balancing "hands-on" with "hands-off" physical therapy interventions for the treatment of central sensitization pain in osteoarthritis.

PubMed

Lluch Girbés, E; Meeus, M; Baert, I; Nijs, J

2015-04-01

Traditional understanding of osteoarthritis-related pain has recently been challenged in light of evidence supporting a key role of central sensitization in a subgroup of this population. This fact may erroneously lead musculoskeletal therapists to conclude that hands-on interventions have no place in OA management, and that hands-off interventions must be applied exclusively. The aim of this paper is to encourage clinicians in finding an equilibrium between hands-on and hands-off interventions in patients with osteoarthritis-related pain dominated by central sensitization. The theoretical rationale for simultaneous application of manual therapy and pain neuroscience education is presented. Practical problems when combining these interventions are also addressed. Future studies should explore the combined effects of these treatment strategies to examine whether they increase therapeutic outcomes against current approaches for chronic osteoarthritis-related pain. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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.

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

The role of state anxiety in children's memories for pain.

PubMed

Noel, Melanie; Chambers, Christine T; McGrath, Patrick J; Klein, Raymond M; Stewart, Sherry H

2012-06-01

To investigate the impact of experimentally manipulated state anxiety and the influence of anxiety-related variables on children's memories for pain. A total of 110 children (60 boys) between the ages of 8 and 12 years were randomly assigned to complete a state anxiety induction task or a control task. Following experimental manipulation, children completed a laboratory pain task, pain ratings, and questionnaire measures of anxiety-related variables. 2 weeks later, children provided pain ratings based on their memories of the pain task. The experimental manipulation effectively induced state anxiety; however, pain memories did not differ between groups. Irrespective of group assignment, children with higher state anxiety had more negative pain memories. State anxiety uniquely predicted children's pain memories over and above other well established factors. Anxiety sensitivity and trait anxiety were significant predictors of recalled pain-related fear. These data highlight the importance of anxiety in the development of children's memories for pain.

Central Sensitivity Syndromes: Mounting Pathophysiologic Evidence to Link Fibromyalgia with other Common Chronic Pain Disorders

PubMed Central

Kindler, Lindsay L.; Bennett, Robert M.; Jones, Kim D.

2009-01-01

Objective To review emerging data from the fields of nursing, rheumatology, dentistry, gastroenterology, gynecology, neurology, and orthopedics that supports or disputes pathophysiologic similarities in pain syndromes studied by each specialty. Methods A literature search was performed through PubMed and Ovid using the terms fibromyalgia, temporomandibular joint disorder, irritable bowel syndrome, irritable bladder/interstitial cystitis, headache, chronic low back pain, chronic neck pain, functional syndromes and somatization. Each term was linked with pathophysiology and/or central sensitization. This paper presents a review of relevant articles with a specific goal of identifying pathophysiological findings related to nociceptive processing. Results The extant literature presents considerable overlap in the pathophysiology of these diagnoses. Given the psychosomatic lens through which many of these disorders are viewed, demonstration of evidence based links supporting shared pathophysiology between these disorders could provide direction to clinicians and researchers working to treat these diagnoses. Conclusions Central sensitivity syndromes denotes an emerging nomenclature that could be embraced by researchers investigating each of these disorders. Moreover, a shared paradigm would be useful in promoting cross-fertilization between researchers. Scientists and clinicians could most effectively forward the understanding and treatment of fibromyalgia and other common chronic pain disorders through an appreciation of their shared pathophysiology. PMID:21349445

Pain sensitivity in patients with haemophilia following moderate aerobic exercise intervention.

PubMed

Krüger, S; Weitz, C; Runkel, B; Hilberg, T

2016-11-01

Physical activity is influenced by pain and vice versa. Although studies recommend exercise therapy for patients with haemophilia (PwH), the influence of physical activity on the pain condition in PwH has not been investigated so far. Aim of this study was to examine the effect of a treadmill intervention with self-chosen velocity on the acute pain sensitivity in PwH. Twenty PwH [aged 24-58 years, moderate (n = 3) to severe (n = 17) haemophilia A (n = 17) or B (n = 3)] and 20 control subjects (aged 26-61 years) were included in this study. Eighteen PwH and all controls completed a treadmill intervention for 30 min. Pressure pain thresholds (PPT) in Newton (N) were measured at both the knees, ankles and elbows, sternum and forehead before (pre) and immediately after walking (post). PwH and controls walked with comparable speed (mean speed in km h -1 ; PwH: 3.5, controls: 3.8), resulting in significantly different values of performance-related parameters such as heart rate (mean heart rate per minute; PwH: 102, controls: 86; P ≤ 0.01). Compared to baseline values, PPT remained unaltered at all landmarks in both groups after walking (e.g. pre/post in Newton; knee right: PwH: 63.1/63.0, controls: 93.8/93.8; left knee: PwH: 62.1/62.7, controls: 90.0/93.4), indicating a non-increasing pain condition. Findings of unaltered PPT following moderate aerobic exercise showed initial evidence that PwH are able to perform an endurance exercise with self-chosen velocity for 30 min as recommended, without increasing the acute pain condition. By doing so, PwH can benefit from the positive effects of endurance exercise. © 2016 John Wiley & Sons Ltd.

Improving understanding of trigger points and widespread pressure pain sensitivity in tension-type headache patients: clinical implications.

PubMed

Fernández-De-Las-Peñas, César; Arendt-Nielsen, Lars

2017-09-01

The underlying etiology of tension type headache (TTH) is not understood. The current paper highlights the etiologic role of muscle trigger points (TrPs) to the development and maintenance of central sensitization in TTH and its clinical repercussion for proper management of these patients. Areas covered: A literature search on Pub Med for English-language published papers between 1990 and May 2017 to provide the most updated data on the topic was conducted. Current literature suggests that the referred pain elicited by active trigger points (TrPs) contributes to the manifestations of TTH. There is also evidence supporting that TrPs represent a peripheral source of nociception and thereby a driver in the development of central sensitization. In fact, TrPs have been found to be associated with widespread pressure pain sensitivity in TTH. Temporal and spatial summation of TrP nociception suggests that inactivating TrP in the neck, head and shoulder muscles could help these patients; however, current evidence supporting the therapeutic role of TrPs in TTH is conflicting. Expert commentary: Understanding the role of TrPs in TTH in widespread pain sensitization may help to develop better management regimes and possibly prevent TTH from developing into more chronic conditions.

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.

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin in the evaluation of acute chest pain of uncertain etiology. A PITAGORAS substudy.

PubMed

Sanchis, Juan; Bardají, Alfredo; Bosch, Xavier; Loma-Osorio, Pablo; Marín, Francisco; Sánchez, Pedro L; Calvo, Francisco; Avanzas, Pablo; Hernández, Carolina; Serrano, Silvia; Carratalá, Arturo; Barrabés, José A

2013-07-01

High-sensitivity troponin assays have improved the diagnosis of acute coronary syndrome in patients presenting with chest pain and normal troponin levels as measured by conventional assays. Our aim was to investigate whether N-terminal pro-brain natriuretic peptide provides additional information to troponin determination in these patients. A total of 398 patients, included in the PITAGORAS study, presenting to the emergency department with chest pain and normal troponin levels as measured by conventional assay in 2 serial samples (on arrival and 6 h to 8h later) were studied. The samples were also analyzed in a central laboratory for high-sensitivity troponin T (both samples) and for N-terminal pro-brain natriuretic peptide (second sample). The endpoints were diagnosis of acute coronary syndrome and the composite endpoint of in-hospital revascularization or a 30-day cardiac event. Acute coronary syndrome was adjudicated to 79 patients (20%) and the composite endpoint to 59 (15%). When the N-terminal pro-brain natriuretic peptide quartile increased, the diagnosis of acute coronary syndrome also increased (12%, 16%, 23% and 29%; P=.01), as did the risk of the composite endpoint (6%, 13%, 16% and 24%; P=.004). N-terminal pro-brain natriuretic peptide elevation (>125ng/L) was associated with both endpoints (relative risk= 2.0; 95% confidence interval, 1.2-3.3; P=.02; relative risk=2.4; 95% confidence interval, 1.4-4.2; P=.004). However, in the multivariable models adjusted by clinical and electrocardiographic data, a predictive value was found for high-sensitivity T troponin but not for N-terminal pro-brain natriuretic peptide. In low-risk patients with chest pain of uncertain etiology evaluated using high-sensitivity T troponin, N-terminal pro-brain natriuretic peptide does not contribute additional predictive value to diagnosis or the prediction of short-term outcomes. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights

Factors influencing the attitudes of cattle veterinarians, farmers, and claw trimmers towards the pain associated with the treatment of sole ulcers and the sensitivity to pain of dairy cows.

PubMed

Becker, Johanna; Reist, Martin; Steiner, Adrian

2014-04-01

This study assessed the attitudes of personnel involved in therapeutic claw trimming of dairy cattle in Switzerland towards pain associated with sole ulcers and their treatment. Data from 77 farmers, 32 claw trimmers, and 137 cattle veterinarians were used. A large range of factors were associated with whether the respondents thought that anaesthesia during the treatment of sole ulcers was beneficial; these included year of graduation, work experience, attitude to costs of analgesia, perception of competition between veterinarians and claw trimmers, estimation of pain level associated with treatment, estimated sensitivity of dairy cows to pain, knowledge of the obligation to provide analgesia, and whether the respondent thought lesion size and occurrence of defensive behaviour by the cow were important. Respondents' estimation of the pain level associated with sole ulcer treatment was linked to frequency of therapeutic claw trimming, age, farmers' income, estimated knowledge of the benefits of analgesia, and estimated sensitivity of dairy cows to pain. The latter factor was associated with profession, frequency of therapeutic claw trimming, capability of pain recognition, opinion on the benefits of analgesia, knowledge of the obligation to provide analgesia, and self-estimation of the ability to recognise pain. Improving the knowledge of personnel involved in therapeutic claw trimming with regard to pain in dairy cows and how to alleviate it is crucial if management of pain associated with treatment of sole ulcer and the welfare of lame cows are to be optimised. Copyright © 2014 Elsevier Ltd. All rights reserved.

Muscle pain sensitivity after glutamate injection is not modified by systemic administration of monosodium glutamate.

PubMed

Shimada, Akiko; Castrillon, Eduardo; Baad-Hansen, Lene; Ghafouri, Bijar; Gerdle, Björn; Ernberg, Malin; Cairns, Brian; Svensson, Peter

2015-01-01

Monosodium glutamate (MSG) is often thought to be associated with headache and craniofacial pains like temporomandibular disorders. This randomized, double-blinded, placebo-controlled study was performed to investigate how ingestion of MSG affects muscle pain sensitivity before and after experimentally induced muscle pain. Sixteen healthy adult subjects participated in 2 sessions with at least 1-week interval between sessions. In each session, two injections of glutamate (Glu, 0.5 M, 0.2 ml) and two injections of saline (0.9%, 0.2 ml) into the masseter and temporalis muscles, respectively, were undertaken, with a 15 min interval between each injection. Injections of saline were made contralateral to Glu injections and done in a randomized order. Participants drank 400 mL of soda mixed with either MSG (150 mg/kg) or NaCl (24 mg/kg, placebo) 30 min before the intramuscular injections. Pressure pain thresholds (PPT), autonomic parameters and pain intensity were assessed prior to (baseline) and 30 min after ingestion of soda, as well as 5 min and 10 min after the intramuscular injections and at the end of the session. Whole saliva samples were collected prior to and 30, 45, 60, and 75 min after the ingestion of soda. MSG administration resulted in a significantly higher Glu level in saliva than administration of NaCl and was associated with a significant increase in systolic blood pressure. Injections of Glu were significantly more painful than injections of NaCl. However, ingestion of MSG did not change the intensity of Glu-evoked pain. Glu injections also significantly increased systolic and diastolic blood pressure, but without an additional effect of MSG ingestion. Glu injections into the masseter muscle significantly reduced the PPT. However, pre-injection MSG ingestion did not significantly alter this effect. Interestingly, PPT was significantly increased in the trapezius after MSG ingestion and intramuscular injection of Glu in the jaw muscles. The main finding

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.

Implementation of specific strength training among industrial laboratory technicians: long-term effects on back, neck and upper extremity pain.

PubMed

Pedersen, Mogens Theisen; Andersen, Christoffer H; Zebis, Mette K; Sjøgaard, Gisela; Andersen, Lars L

2013-10-09

Previous studies have shown positive effects of physical exercise at the workplace on musculoskeletal disorders. However, long-term adherence remains a challenge. The present study evaluates long-term adherence and effects of a workplace strength training intervention on back, neck and upper extremity pain among laboratory technicians. Cluster-randomized controlled trial involving 537 industrial laboratory technicians. Subjects were randomized at the cluster level to one of two groups: training group 1 (TG1, n = 282) performing supervised strength training from February to June 2009 (round one) or training group 2 (TG2, n = 255) performing supervised strength training from August to December 2009 (round two). The outcome measures were changes in self-reported pain intensity (0-9) in the back, neck and upper extremity as well as Disability of the Arm, Shoulder and Hand (DASH, 0-100). Regular adherence, defined as at least one training session per week, was achieved by around 85% in both groups in the supervised training periods. In the intention-to-treat analyses there were significant group by time effects for pain in the neck, right shoulder, right hand and lower back and DASH-resulting in significant reductions in pain (mean 0.3 to 0.5) and DASH (mean 3.9) in the scheduled training group compared to the reference group. For TG1 there were no significant changes in pain in round two, i.e. they maintained the pain reduction achieved in round one. Subgroup analyses among those with severe pain (> = 3 on a scale of 0-9) showed a significant group by time effect for pain in the neck, right shoulder, upper back and lower back. For these subgroups the pain reduction in response to training ranged from 1.1 to 1.8. Specific strength training at the workplace can lead to significant long-term reductions in spinal and upper extremity pain and DASH. The pain reductions achieved during the intensive training phase with supervision appears to be maintained a half

The influence of children's pain memories on subsequent pain experience.

PubMed

Noel, Melanie; Chambers, Christine T; McGrath, Patrick J; Klein, Raymond M; Stewart, Sherry H

2012-08-01

Healthy children are often required to repeatedly undergo painful medical procedures (eg, immunizations). Although memory is often implicated in children's reactions to future pain, there is a dearth of research directly examining the relationship between the 2. The current study investigated the influence of children's memories for a novel pain stimulus on their subsequent pain experience. One hundred ten healthy children (60 boys) between the ages of 8 and 12 years completed a laboratory pain task and provided pain ratings. Two weeks later, children provided pain ratings based on their memories as well as their expectancies about future pain. One month following the initial laboratory visit, children again completed the pain task and provided pain ratings. Results showed that children's memory of pain intensity was a better predictor of subsequent pain reporting than their actual initial reporting of pain intensity, and mediated the relationship between initial and subsequent pain reporting. Children who had negatively estimated pain memories developed expectations of greater pain prior to a subsequent pain experience and showed greater increases in pain ratings over time than children who had accurate or positively estimated pain memories. These findings highlight the influence of pain memories on healthy children's expectations of future pain and subsequent pain experiences and extend predictive models of subsequent pain reporting. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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.

Immediate changes in widespread pressure pain sensitivity, neck pain, and cervical range of motion after cervical or thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain: a randomized clinical trial.

PubMed

Martínez-Segura, Raquel; De-la-Llave-Rincón, Ana I; Ortega-Santiago, Ricardo; Cleland, Joshua A; Fernández-de-Las-Peñas, César

2012-09-01

Randomized clinical trial. To compare the effects of cervical versus thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain on pressure pain sensitivity, neck pain, and cervical range of motion (CROM). Evidence suggests that spinal interventions can stimulate descending inhibitory pain pathways. To our knowledge, no study has investigated the neurophysiological effects of thoracic thrust manipulation in individuals with bilateral chronic mechanical neck pain, including widespread changes on pressure sensitivity. Ninety patients (51% female) were randomly assigned to 1 of 3 groups: cervical thrust manipulation on the right, cervical thrust manipulation on the left, or thoracic thrust manipulation. Pressure pain thresholds (PPTs) over the C5-6 zygapophyseal joint, lateral epicondyle, and tibialis anterior muscle, neck pain (11-point numeric pain rating scale), and cervical spine range of motion (CROM) were collected at baseline and 10 minutes after the intervention by an assessor blinded to the treatment allocation of the patients. Mixed-model analyses of covariance were used to examine the effects of the treatment on each outcome variable, with group as the between-subjects variable, time and side as the within-subject variables, and gender as the covariate. The primary analysis was the group-by-time interaction. No significant interactions were found with the mixed-model analyses of covariance for PPT level (C5-6, P>.210; lateral epicondyle, P>.186; tibialis anterior muscle, P>.268), neck pain intensity (P = .923), or CROM (flexion, P = .700; extension, P = .387; lateral flexion, P>.672; rotation, P>.192) as dependent variables. All groups exhibited similar changes in PPT, neck pain, and CROM (all, P<.001). Gender did not influence the main effects or the interaction effects in the analyses of the outcomes (P>.10). The results of the current randomized clinical trial suggest that cervical and thoracic thrust manipulation induce similar

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

The Rat Grimace Scale: A partially automated method for quantifying pain in the laboratory rat via facial expressions

PubMed Central

2011-01-01

We recently demonstrated the utility of quantifying spontaneous pain in mice via the blinded coding of facial expressions. As the majority of preclinical pain research is in fact performed in the laboratory rat, we attempted to modify the scale for use in this species. We present herein the Rat Grimace Scale, and show its reliability, accuracy, and ability to quantify the time course of spontaneous pain in the intraplantar complete Freund's adjuvant, intraarticular kaolin-carrageenan, and laparotomy (post-operative pain) assays. The scale's ability to demonstrate the dose-dependent analgesic efficacy of morphine is also shown. In addition, we have developed software, Rodent Face Finder®, which successfully automates the most labor-intensive step in the process. Given the known mechanistic dissociations between spontaneous and evoked pain, and the primacy of the former as a clinical problem, we believe that widespread adoption of spontaneous pain measures such as the Rat Grimace Scale might lead to more successful translation of basic science findings into clinical application. PMID:21801409

Pain perception and nonsuicidal self-injury: a laboratory investigation.

PubMed

Hooley, Jill M; Ho, Doreen T; Slater, Joshua; Lockshin, Amanda

2010-07-01

People who engage in self-injurious behaviors such as cutting and burning may have altered pain perception. Using a community sample, we examined group differences in pain threshold and pain endurance between participants who self-injured and control participants who were exposed to pressure pain applied to the finger. Participants who self-injured had higher pain thresholds (time to report pain) and endured pain for longer than control participants. Among participants who self-injured, those with longer histories of self-injury had higher pain thresholds. Duration of self-injury was unrelated to pain endurance. Instead, greater pain endurance was predicted by higher levels of introversion and neuroticism and by more negative beliefs about one's self-worth. A highly self-critical cognitive style was the strongest predictor of prolonged pain endurance. People who self-injure may regard suffering and pain as something that they deserve. Our findings also have implications for understanding factors that might be involved in the development and maintenance of self-injury. PsycINFO Database Record (c) 2010 APA, all rights reserved

Sex and gender differences in pain and analgesia.

PubMed

Mogil, Jeffrey S; Bailey, Andrea L

2010-01-01

It is a clinical reality that women make up the large majority of chronic pain patients, and there is now consensus from laboratory experiments that when differences are seen, women are more sensitive to pain than men. Research in this field has now begun to concentrate on finding explanations for this sex difference. Although sex differences in sociocultural, psychological, and experiential factors likely play important roles, evidence largely from animal studies has revealed surprisingly robust and often qualitative sex differences at low levels of the neuraxis. Although not yet able to affect clinical practice, the continued study of sex differences in pain may have important implications for the development of new analgesic strategies. Copyright © 2010 Elsevier B.V. All rights reserved.

Effects of cardiopulmonary baroreceptor activation on pain may be moderated by risk for hypertension.

PubMed

Ditto, Blaine; Lewkowski, Maxim D; Rainville, Pierre; Duncan, Gary H

2009-10-01

Cardiopulmonary baroreceptor stimulation may modulate pain, though the literature is much smaller than research showing that sinoaortic baroreceptor stimulation can buffer pain. To examine the possibility that risk for established high blood pressure may moderate the effects of cardiopulmonary baroreceptor stimulation on pain, 22 borderline hypertensive and 18 normotensive men participated in a laboratory experiment. Group differences in blood pressure were documented by 24-h ambulatory blood pressure recording. Ratings of the intensity of acute heat pain were influenced by both group membership and leg position. Passive elevation of the legs, a technique that stimulates cardiopulmonary baroreceptors, reduced ratings of heat pain though only among borderline hypertensives. Alteration of pain sensitivity may reflect the development of the hypertensive process.

Report on first certificate course on applied physiology of pain, analgesia, anesthesia, and euthanasia for laboratory animals held in Sri Lanka.

PubMed

Gunatilake, Mangala

2018-06-01

Similar to human beings, pain is an unpleasant sensation experienced by animals as well. There is no exception when the animals are subjected to experimental procedures. Our duty as researchers/scientists is to prevent or minimize the pain in animals so as to lessen their suffering and distress during experimental procedures. The basics of the physiology of pain and pain perception, analgesia, anesthesia, and euthanasia of laboratory animals were included to complete the program, before the practical part was attempted and before advanced topics, such as comparison of anesthetic combinations, were discussed. Therefore, this course was organized in Sri Lanka for the first time in collaboration with the Comparative Biology Centre of Newcastle University, UK. During this course, we were able to demonstrate how an anesthesia machine could be used in laboratory animal anesthesia for the first time in the country. None of the animal houses in the country were equipped with an anesthesia machine at the time of conducting the course.

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.

Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain

PubMed Central

Khasabov, Sergey G.; Hamamoto, Darryl T.; Harding-Rose, Catherine; Simone, Donald A.

2009-01-01

Pain associated with cancer, particularly when tumors metastasize to bone, is often severe and debilitating. Better understanding of the neurobiological mechanisms underlying cancer pain will likely lead to the development of more effective treatments. The aim of this study was to characterize changes in response properties of nociceptive dorsal horn neurons following implantation of fibrosarcoma cells into and around the calcaneus bone, an established model of cancer pain. Extracellular electrophysiological recordings were made from wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons in mice with tumor-evoked hyperalgesia and control mice. WDR and HT neurons were examined for ongoing activity and responses to mechanical, heat, and cold stimuli applied to the plantar surface of the hind paw. Behavioral experiments showed that mice exhibited hyperalgesia to mechanical and heat stimuli applied to their tumor-bearing hind paw. WDR, but not HT, nociceptive dorsal horn neurons in tumor-bearing mice exhibited sensitization to mechanical, heat, and cold stimuli and may contribute to tumor-evoked hyperalgesia. Specifically, the proportion of WDR neurons that exhibited ongoing activity and their evoked discharge rates were greater in tumor-bearing than in control mice. In addition, WDR neurons exhibited lower response thresholds for mechanical and heat stimuli, and increased responses to suprathreshold mechanical, heat, and cold stimuli. Our findings show that sensitization of WDR neurons contribute to cancer pain and support the notion that the mechanisms underlying cancer pain differ from those that contribute to inflammatory and neuropathic pain. PMID:17935703

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

Pain Reduces Sexual Motivation in Female But Not Male Mice

PubMed Central

Farmer, Melissa A.; Leja, Alison; Foxen-Craft, Emily; Chan, Lindsey; MacIntyre, Leigh C.; Niaki, Tina; Chen, Mengsha; Mapplebeck, Josiane C.S.; Tabry, Vanessa; Topham, Lucas; Sukosd, Melissa; Binik, Yitzchak M.; Pfaus, James G.

2014-01-01

Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected. PMID:24760835

Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome

PubMed Central

Theodorou, Vassilia; Belgnaoui, Afifa Ait; Agostini, Simona; Eutamene, Helene

2014-01-01

The last ten years’ wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient’s quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation. PMID:25184834

Do Australian Football players have sensitive groins? Players with current groin pain exhibit mechanical hyperalgesia of the adductor tendon.

PubMed

Drew, Michael K; Lovell, Gregory; Palsson, Thorvaldur S; Chiarelli, Pauline E; Osmotherly, Peter G

2016-10-01

This is the first study to evaluate the mechanical sensitivity, clinical classifications and prevalence of groin pain in Australian football players. Case-control. Professional (n=66) and semi-professional (n=9) Australian football players with and without current or previous groin injuries were recruited. Diagnoses were mapped to the Doha Agreement taxonomy. Point and career prevalence of groin pain was calculated. Pressure pain thresholds (PPTs) were assessed at regional and distant sites using handheld pressure algometry across four sites bilaterally (adductor longus tendon, pubic bone, rectus femoris, tibialis anterior muscle). To assess the relationship between current groin pain and fixed effects of hyperalgesia of each site and a history of groin pain, a mixed-effect logistic regression model was utilised. Receiver Operator Characteristic (ROC) curve were determined for the model. Point prevalence of groin pain in the preseason was 21.9% with a career prevalence of 44.8%. Adductor-related groin pain was the most prevalent classification in the pre-season period. Hyperalgesia was observed in the adductor longus tendon site in athletes with current groin pain (OR=16.27, 95% CI 1.86 to 142.02). The ROC area under the curve of the regression model was fair (AUC=0.76, 95% CI 0.54 to 0.83). Prevalence data indicates that groin pain is a larger issue than published incidence rates imply. Adductor-related groin pain is the most common diagnosis in pre-season in this population. This study has shown that hyperalgesia exists in Australian football players experiencing groin pain indicating the value of assessing mechanical pain sensitivity as a component of the clinical assessment. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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.

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.

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

Painful neurotrophins and their role in visceral pain.

PubMed

López-Pérez, Ana E; Nurgali, Kulmira; Abalo, Raquel

2018-04-01

Beyond their well-known role in embryonic development of the central and peripheral nervous system, neurotrophins, particularly nerve growth factor and brain-derived neurotrophic factor, exert an essential role in pain production and sensitization. This has mainly been studied within the framework of somatic pain, and even antibodies (tanezumab and fasinumab) have recently been developed for their use in chronic somatic painful conditions, such as osteoarthritis or low back pain. However, data suggest that neurotrophins also exert an important role in the occurrence of visceral pain and visceral sensitization. Visceral pain is a distressing symptom that prompts many consultations and is typically encountered in both 'organic' (generally inflammatory) and 'functional' (displaying no obvious structural changes in routine clinical evaluations) disorders of the gut, such as inflammatory bowel disease and irritable bowel syndrome, respectively. The present review provides a summary of neurotrophins as a molecular family and their role in pain in general and addresses recent investigations of the involvement of nerve growth factor and brain-derived neurotrophic factor in visceral pain, particularly that associated with inflammatory bowel disease and irritable bowel syndrome.

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

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.

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.

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

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

Increased pain sensitivity is not associated with electrodiagnostic findings in women with carpal tunnel syndrome.

PubMed

de la Llave-Rincón, Ana Isabel; Fernández-de-las-Peñas, César; Laguarta-Val, Sofia; Alonso-Blanco, Cristina; Martínez-Perez, Almudena; Arendt-Nielsen, Lars; Pareja, Juan A

2011-01-01

To determine the differences in widespread pressure pain and thermal hypersensitivity in women with minimal, moderate, and severe carpal tunnel syndrome (CTS) and healthy controls. A total of 72 women with CTS (19 with minimal, 18 with moderate, and 35 with severe) and 19 healthy age-matched women participated. Pressure pain thresholds were bilaterally assessed over the median, ulnar, and radial nerves, the C5 to C6 zygapophyseal joint, the carpal tunnel, and the tibialis anterior muscle. In addition, warm and cold detection thresholds and heat and cold pain thresholds were bilaterally assessed over the carpal tunnel and the thenar eminence. All outcome parameters were assessed by an assessor blinded to the participant's condition. No significant differences in pain parameters among patients with minimal, moderate, and severe CTS were found. The results showed that PPT were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, C5 to C6 zygapophyseal joint, and the tibialis anterior muscle in patients with minimal, moderate, or severe CTS as compared with healthy controls (all, P<0.001). In addition, patients with CTS also showed lower heat pain threshold and reduced cold pain threshold compared with controls (P<0.001). No significant sensory differences between minimal, moderate, or severe CTS were found. The similar widespread pressure and thermal hypersensitivity in patients with minimal, moderate, or severe CTS and pain intensity suggests that increased pain sensitivity is not related to electrodiagnostic findings.

Differential effects of repetitive oral administration of monosodium glutamate on interstitial glutamate concentration and muscle pain sensitivity.

PubMed

Shimada, Akiko; Baad-Hansen, Lene; Castrillon, Eduardo; Ghafouri, Bijar; Stensson, Niclas; Gerdle, Björn; Ernberg, Malin; Cairns, Brian; Svensson, Peter; Svensson Odont, Peter

2015-02-01

The aim of this study was to determine the relationship of high daily monosodium glutamate (MSG) consumption with glutamate concentrations in jaw muscle, saliva, and serum, and muscle pain sensitivity in healthy participants. A randomized, double-blinded, placebo-controlled study was conducted to investigate the effect of repetitive consumption of high-dose MSG on glutamate concentration in the masseter muscles measured by microdialysis and muscle pain sensitivity. In five contiguous experimental daily sessions, 32 healthy participants drank MSG (150 mg/kg) or NaCl (24 mg/kg) diluted with a 400 mL soda. The concentrations of glutamate before and after the ingestion were assessed in dialysate and plasma samples on the first and last days. Saliva glutamate concentration was assessed every day. Pressure pain threshold, pressure pain tolerance, autonomic parameters (heart rate, systolic and diastolic blood pressures) and reported side effects also were assessed. No significant change was noted in the baseline concentration of glutamate in the masseter muscle, blood, or saliva, but the peak concentration in the masseter muscle increased significantly between day 1 and 5. A statistically significant increase in systolic and diastolic blood pressures after MSG administration was observed, as well as a significantly higher frequency of reports of nausea and headache in the MSG group. No robust effect of MSG on muscle sensitivity was found. Interstitial glutamate concentration in the masseter muscle is not highly disturbed by excessive repetitive intake of MSG in healthy man. Copyright © 2015 Elsevier Inc. All rights reserved.

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

PubMed

Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-09-01

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P < .0004). Psychoactive and subjective effects were dose-dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. Because the 2 active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

The Cuernos del Paine mountains in Torres del Paine National Park, Chile, during NASA's AirSAR 2004 campaign

NASA Image and Video Library

2004-03-11

The Cuernos del Paine mountains in Torres del Paine National Park, Chile, during NASA's AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. Founded in 1959, Torres del Paine National Park encompasses 450,000 acres in the Patagonia region of Chile. This region is being studied by NASA using a DC-8 equipped with an Airborne Synthetic Aperture Radar (AirSAR) developed by scientists from NASA’s Jet Propulsion Laboratory. This is a very sensitive region that is important to scientists because the temperature has been consistently rising causing a subsequent melting of the region’s glaciers. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain.

PubMed

Liu, S; Liu, Y-P; Yue, D-M; Liu, G-J

2014-03-01

Treating bone cancer pain continues to be a major clinical challenge, and the underlying mechanisms of bone cancer pain remain elusive. Protease-activated receptor 2 (PAR2) has been reported to be involved in neurogenic inflammation, nociceptive pain and hyperalgesia. Here, we investigated the role of PAR2 in bone cancer pain development. Expression of PAR2, mechanical allodynia, thermal hyperalgesia and neurochemical alterations induced by bone cancer pain were analysed in male, adult C3H/HeJ mice with tumour cell implantation (TCI). To investigate the contribution of PAR2 to bone cancer pain, PAR2 antagonist peptide and PAR2 knockout mice were used. TCI produced bone cancer-related pain behaviours. Production and persistence of these pain behaviours were well correlated with TCI-induced up-regulation of PAR2 in sciatic nerve and dorsal root ganglia (DRG). PAR2 knockout and spinal administration of PAR2 antagonist peptide prevented and/or reversed bone cancer-related pain behaviours and associated neurochemical changes in DRG and dorsal horn (DH). TCI also induced proteases release in tumour-bearing tibia, sciatic nerve and DRG. Plantar injection of supernatant from sarcoma cells induced PAR2 up-regulation and intracellular calcium [Ca(2+) ]i increase in DRG, and calcitonin gene-related peptide accumulation in DH, as well as significant thermal and mechanical hyperalgesia, which were all in PAR2-dependent manners. These findings suggest that PAR2 may be a key mediator for peripheral sensitization of bone cancer pain. Inhibiting PAR2 activation, especially during the early phase, may be a new therapy for preventing/suppressing development of bone cancer pain. © 2013 European Pain Federation - EFIC®

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.

Ropivacaine and Bupivacaine prevent increased pain sensitivity without altering neuroimmune activation following repeated social defeat stress.

PubMed

Sawicki, Caroline M; Kim, January K; Weber, Michael D; Jarrett, Brant L; Godbout, Jonathan P; Sheridan, John F; Humeidan, Michelle

2018-03-01

Mounting evidence indicates that stress influences the experience of pain. Exposure to psychosocial stress disrupts bi-directional communication pathways between the central nervous system and peripheral immune system, and can exacerbate the frequency and severity of pain experienced by stressed subjects. Repeated social defeat (RSD) is a murine model of psychosocial stress that recapitulates the immune and behavioral responses to stress observed in humans, including activation of stress-reactive neurocircuitry and increased pro-inflammatory cytokine production. It is unclear, however, how these stress-induced neuroimmune responses contribute to increased pain sensitivity in mice exposed to RSD. Here we used a technique of regional analgesia with local anesthetics in mice to block the development of mechanical allodynia during RSD. We next investigated the degree to which pain blockade altered stress-induced neuroimmune activation and depressive-like behavior. Following development of a mouse model of regional analgesia with discrete sensory blockade over the dorsal-caudal aspect of the spine, C57BL/6 mice were divided into experimental groups and treated with Ropivacaine (0.08%), Liposomal Bupivacaine (0.08%), or Vehicle (0.9% NaCl) prior to exposure to stress. This specific region was selected for analgesia because it is the most frequent location for aggression-associated pain due to biting during RSD. Mechanical allodynia was assessed 12 h after the first, third, and sixth day of RSD after resolution of the sensory blockade. In a separate experiment, social avoidance behavior was determined after the sixth day of RSD. Blood, bone marrow, brain, and spinal cord were collected for immunological analyses after the last day of RSD in both experiments following behavioral assessments. RSD increased mechanical allodynia in an exposure-dependent manner that persisted for at least one week following cessation of the stressor. Mice treated with either Ropivacaine or

Pressure pain sensitivity topographical maps reveal bilateral hyperalgesia of the hands in patients with unilateral carpal tunnel syndrome.

PubMed

Fernández-de-Las-Peñas, César; Madeleine, Pascal; Martínez-Perez, Almudena; Arendt-Nielsen, Lars; Jiménez-García, Rodrigo; Pareja, Juan A

2010-08-01

To assess topographical pressure pain sensitivity maps of the hand in patients with unilateral carpal tunnel syndrome (CTS) as compared with healthy subjects. A total of 20 women with CTS (ages 32-52 years) and 20 healthy matched women (ages 32-51 years) were recruited. Pressure pain thresholds (PPTs) were measured bilaterally over 30 locations of the palm of each hand by an assessor blinded to the subjects' conditions. Patients showed lower PPTs in both hands in all of the measurement points as compared with controls (P < 0.001 for all). PPTs were lower in those points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers (P < 0.001). CTS patients showed lower PPT levels in dermatomes C6, C7, and C8 when compared with healthy controls (P < 0.001 for all), but without differences between dermatomes (P = 0.4). PPT was negatively correlated with both hand pain intensity and duration of symptoms (P < 0.001 for all). Our findings revealed bilateral generalized pressure pain hyperalgesia in unilateral CTS because lower PPT levels were found in all of the points. The pressure pain hyperalgesia was not uniformly distributed since PPTs were lower in points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers. The decrease in PPT levels was associated with the intensity and the duration of the pain symptoms, supporting a role of both peripheral and central sensitization mechanisms in this pain condition.

The Nature of the Association between Anxiety Sensitivity and Pain-Related Anxiety: Evidence from Correlational and Intervention Studies.

PubMed

Olthuis, Janine V; Watt, Margo C; Mackinnon, Sean P; Potter, Susan M; Stewart, Sherry H

2015-01-01

High anxiety sensitivity (AS) has been associated with elevated pain-related anxiety in anxiety and pain samples. The present study investigated (a) the associations among the lower order dimensions of AS and pain-related anxiety, using a robust measure of AS, and (b) the pain-related anxiety outcomes of a telephone-delivered cognitive behavioural treatment (CBT) designed to reduce high AS. Participants were 80 anxiety treatment-seeking participants with high AS (M age = 36 years; 79% women). After providing baseline data on AS and pain-related anxiety, participants were randomly assigned to an eight-week telephone CBT or a waiting list control. At baseline, bivariate correlations showed AS physical and cognitive, but not social, concerns were significantly associated with pain-related fear and arousal but not escape/avoidance behaviours. Multiple regression revealed that after accounting for emotional distress symptoms, AS physical, but not cognitive or social, concerns uniquely predicted pain-related anxiety. Multilevel modelling showed that the AS-targeted CBT reduced pain-related anxiety and treatment-related changes in global AS and AS physical concerns mediated changes in pain-related anxiety. Results suggest that an AS-targeted intervention may have implications for reducing pain-related anxiety. Further research is needed in a chronic pain sample.

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.

[Musculoskeletal pain].

PubMed

Casser, H-R; Schaible, H-G

2015-10-01

Among the clinically relevant pain conditions, pain in the musculoskeletal system is most frequent. This article reports extensive epidemiological data on musculoskeletal system pain in Germany and worldwide. Since back pain is most frequent, the diagnostics and therapeutic algorithms of acute, recurring, and chronic lower back pain in Germany will be particularly addressed. The importance of the physiologic-organic, the cognitive-emotional, the behavioral, and the social level to diagnostics and treatment will be discussed. We will also focus on osteoarthritic pain and address its epidemiology, clinical importance, and significance for the health care system. This article will list some reasons why the musculoskeletal system in particular is frequently the site of chronic pain. The authors believe that these reasons are to be sought in the complex structures of the musculoskeletal system; in the particular sensitivity of the deep somatic nociceptive system for long-term sensitization processes, as well as the ensuing nervous system reactions; and in the interactions between the nervous and immune systems. The article will give some insights into the research carried out on this topic in Germany.

Pressure pain sensitivity as a marker for stress and pressure pain sensitivity-guided stress management in women with primary breast cancer.

PubMed

Axelsson, Christen K; Ballegaard, Søren; Karpatschof, Benny; Schousen, Peer

2014-08-01

To validate (1) Pressure Pain Sensitivity (PPS) as a marker for stress and (2) a PPS-guided intervention in women with primary Breast Cancer (BC). (1) A total of 58 women with BC were examined before and after 6 months of intervention. A control group of 165 women office employees was divided in a High Stress Group (HSG, n = 37) and a Low Stress Group (LSG, n = 128) to evaluate the association between PPS, questionnaire-related Quality of Life (QOL) and self-evaluated stress. (2) A PPS-guided stress management program (n = 40) was compared to a Psychosocial Group Intervention (PGI, n = 91) and no treatment (n = 86) with respect to a European Organization for Research and Treatment of Cancer (EORTC) questionnaire measured QOL. (1) Resting PPS and changes in PPS during the intervention period correlated significantly to EORTC and Short Form 36 (SF 36) main scores: (all p < 0.05). Between BC, HSG and LSG there was a significant and positive correlation with respect to PPS, SF 36 main scores, depression, and clinical stress scores (all p < 0.05). However, the BC group scored significantly lower than both HSG and LSG (both p < 0.05) with respect to self-evaluated stress. (2) The PPS-guided intervention group improved EORTC main score, pain and nausea, when compared to the control groups (all p < 0.05). PPS was positively associated with QOL, which was in contrast to self-evaluated stress. PPS-guided intervention improved QOL in women with breast cancer.

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

Assessment of post-laparotomy pain in laboratory mice by telemetric recording of heart rate and heart rate variability

PubMed Central

Arras, Margarete; Rettich, Andreas; Cinelli, Paolo; Kasermann, Hans P; Burki, Kurt

2007-01-01

Background Pain of mild to moderate grade is difficult to detect in laboratory mice because mice are prey animals that attempt to elude predators or man by hiding signs of weakness, injury or pain. In this study, we investigated the use of telemetry to identify indicators of mild-to-moderate post-laparotomy pain. Results Adult mice were subjected to laparotomy, either combined with pain treatment (carprofen or flunixin, 5 mg/kg s/c bid, for 1 day) or without pain relief. Controls received anesthesia and analgesics or vehicle only. Telemetrically measured locomotor activity was undisturbed in all animals, thus confirming that any pain experienced was of the intended mild level. No symptoms of pain were registered in any of the groups by scoring the animals' outer appearance or spontaneous and provoked behavior. In contrast, the group receiving no analgesic treatment after laparotomy demonstrated significant changes in telemetry electrocardiogram recordings: increased heart rate and decreased heart rate variability parameters pointed to sympathetic activation and pain lasting for 24 hours. In addition, core body temperature was elevated. Body weight and food intake were reduced for 3 and 2 days, respectively. Moreover, unstructured cage territory and destroyed nests appeared for 1–2 days in an increased number of animals in this group only. In controls these parameters were not affected. Conclusion In conclusion, real-time telemetric recordings of heart rate and heart rate variability were indicative of mild-to-moderate post-laparotomy pain and could define its duration in our mouse model. This level of pain cannot easily be detected by direct observation. PMID:17683523

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

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®.

Sensitization of TRPV1 receptors by TNF-α orchestrates the development of vincristine-induced pain.

PubMed

Wang, Ying; Feng, Chenyang; He, Haoying; He, Jinjin; Wang, Jun; Li, Xiaomin; Wang, Shasha; Li, Wei; Hou, Jiuzhou; Liu, Tong; Fang, Dong; Xie, Song-Qiang

2018-04-01

Vincristine is one of the most common anticancer drugs clinically employed in the treatment of various malignancies. A major side effect associated with vincristine is the development of neuropathic pain, which is not readily relieved by available analgesics. Although efforts have been made to identify the pathogenesis of vincristine-induced neuropathic pain, the mechanisms underlying its pathogenesis have not been fully elucidated. In the present study, a neuropathic pain model was established in Sprague-Dawley rats by intraperitoneal injection of vincristine sulfate. The results demonstrated that vincristine administration induced the upregulation of transient receptor potential cation channel subfamily V member 1 (TRPV1) protein expression and current density in dorsal root ganglion (DRG) nociceptive neurons. Consistently, inhibition of TRPV1 with capsazepine alleviated vincristine-induced mechanical allodynia and thermal hyperalgesia in rats. Furthermore, vincristine administration induced the upregulation of tumor necrosis factor (TNF)-α production in DRGs, and inhibition of TNF-α synthesis with thalidomide in vivo reversed TRPV1 protein expression, as well as pain hypersensitivity induced by vincristine in rats. The present results suggested that TNF-α could sensitize TRPV1 by promoting its expression, thus leading to mechanical allodynia and thermal hyperalgesia in vincristine-treated rats. Taken together, these findings may enhance our understanding of the pathophysiological mechanisms underlying vincristine-induced pain.

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

PubMed

Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

2017-08-01

The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

The sensitivity of aquatic insects to divalent metals: a comparative analysis of laboratory and field data.

PubMed

Brix, Kevin V; DeForest, David K; Adams, William J

2011-09-15

Laboratory studies have traditionally indicated that aquatic insects are relatively insensitive to metals while field studies have suggested them to be among the most sensitive aquatic invertebrate taxa. We reviewed and synthesized available studies in the literature to critically assess why this discrepancy exists. Despite the intense effort to study the effects of metals on aquatic biota over the past several decades, we found studies specific to insects to still be relatively limited. In general, the discrepancy between laboratory and field studies continues with few efforts having been made to elucidate the ecological and physiological mechanisms that underlie the relative sensitivity (or insensitivity) of aquatic insects to metals. However, given the limited data available, it appears that aquatic insects are indeed relatively insensitive to acute metal exposures. In contrast, we suggest that some aquatic insect taxa may be quite sensitive to chronic metal exposure and in some cases may not be protected by existing water quality criteria for metals. The discrepancy between laboratory and field studies with respect to chronic sensitivity appears to largely be driven by the relatively short exposure periods in laboratory studies as compared to field studies. It also appears that, in some cases, the sensitivity of aquatic insects in field studies may be the result of direct effects on primary producers, which lead to indirect effects via the food chain on aquatic insects. Finally, available evidence suggests that diet is an important source of metal accumulation in insects, but to date there have been no conclusive studies evaluating whether dietary metal accumulation causes toxicity. There is a clear need for developing a more mechanistic understanding of aquatic insect sensitivity to metals in long-term laboratory and field studies. Copyright © 2011 Elsevier B.V. All rights reserved.

No change in rectal sensitivity after gut-directed hypnotherapy in children with functional abdominal pain or irritable bowel syndrome.

PubMed

Vlieger, A M; van den Berg, M M; Menko-Frankenhuis, C; Bongers, M E J; Tromp, E; Benninga, M A

2010-01-01

Gut-directed hypnotherapy (HT) has recently been shown to be highly effective in treating children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS). This study was conducted to determine the extent to which this treatment success is because of an improvement in rectal sensitivity. A total of 46 patients (aged 8-18 years) with FAP (n=28) or IBS (n=18) were randomized to either 12 weeks of standard medical therapy (SMT) or HT. To assess rectal sensitivity, a pressure-controlled intermittent distension protocol (barostat) was performed before and after the therapy. Rectal sensitivity scores changed in SMT patients from 15.1+/-7.3 mm Hg at baseline to 18.6+/-8.5 mm Hg after 12 weeks of treatment (P=0.09) and in HT patients from 17.0+/-9.2 mm Hg to 22.5+/-10.1 mm Hg (P=0.09). The number of patients with rectal hypersensitivity decreased from 6 of 18 to 0 of 18 in the HT group (P=0.04) vs. 6 of 20 to 4 of 20 in the SMT group (P=0.67). No relationship was established between treatment success and rectal pain thresholds. Rectal sensitivity scores at baseline were not correlated with intensity, frequency, or duration of abdominal pain. Clinical success achieved with HT cannot be explained by improvement in rectal sensitivity. Furthermore, no association could be found between rectal barostat findings and clinical symptoms in children with FAP or IBS. Further studies are necessary to shed more light on both the role of rectal sensitivity in pediatric FAP and IBS and the mechanisms by which hypnotherapy results in improvement of clinical symptoms.

Sex dimorphism in a mediatory role of the posterior midcingulate cortex in the association between anxiety and pain sensitivity.

PubMed

Kisler, Lee-Bareket; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

2016-11-01

Behavioral studies found greater pain sensitivity in females that vanishes fully or partially when controlling for the emotional state. Furthermore, pain-related brain activation hints at the role of limbic structures in sex differences in pain processing. We aimed to investigate the role of pain-related limbic structures in mediating the relation between subjects' affective state (i.e., anxiety) and pain. Contact heat-evoked potentials (CHEPs) were recorded in 26 healthy subjects (13 males) simultaneously with innocuous (42 °C) baseline and target noxious (52 °C) series of stimuli administered to the left non-dominant volar forearm. The N2 and P2 components were analyzed, and their generators' activity was estimated using standardized low-resolution brain electromagnetic tomography. Thereafter, structural equation modeling (SEM) was applied separately for females and males, examining the mediatory role of the CHEPs' limbic structures generators [posterior midcingulate cortex (pMCC), insula, amygdala, and hippocampus] in the anxiety-pain sensitivity association. Females exhibited greater P2 amplitudes that were highly associated with larger pMCC activity (r = 0.910, p < 0.001). This correlation was also evident in males, though with less strength (r = 0.578, p = 0.039). Moreover, the P2 amplitudes were associated both in females (r = 0.645, p = 0.017) and males (r = 0.608, p = 0.028) with the activity of the amygdala\\hippocampus\\insula. SEM revealed that the relationship between state anxiety and pain ratings was only in females fully mediated via the effect of the pMCC on the P2 amplitude. These findings suggest that sexual dimorphism in anxiety-related brain activity may explain the differences found in CHEPs and the sex-related association between anxiety and pain.

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.

Optimism and the experience of pain: benefits of seeing the glass as half full

PubMed Central

Goodin, Burel R.; Bulls, Hailey W.

2014-01-01

There is a strong body of literature that lends support to the health-promoting effects of an optimistic personality disposition, observed across various physical and psychological dimensions. In accordance with this evidence base, it has been suggested that optimism may positively influence the course and experience of pain. Although the associations among optimism and pain outcomes have only recently begun to be adequately studied, emerging experimental and clinical research links optimism to lower pain sensitivity and better adjustment to chronic pain. This review highlights recent studies that have examined the effects of optimism on the pain experience using samples of individuals with clinically painful conditions as well as healthy samples in laboratory settings. Furthermore, factors such as catastrophizing, hope, acceptance and coping strategies, which are thought to play a role in how optimism exerts its beneficial effects on pain, are also addressed. PMID:23519832

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

Local and Systemic Changes in Pain Sensitivity After 4 Weeks of Calf Muscle Stretching in a Nonpainful Population: A Randomized Trial.

PubMed

Bartholdy, Cecilie; Zangger, Graziella; Hansen, Lisbeth; Ginnerup-Nielsen, Elisabeth; Bliddal, Henning; Henriksen, Marius

2016-07-01

Stretching is often used in clinical practice for a variety of purposes, including pain therapy. The possible mechanism behind the effect of stretching remains to be clarified. To investigate whether 4 weeks of unilateral stretching of the calf muscles would affect local and central pain sensitivity. This study was a randomized assessor-blinded clinical study. Healthy participants (age 18 to 40) were included and randomized. Participants in the intervention group were instructed to perform 2 stretching exercises targeting the calf muscles; 3 times 30 seconds, 7 days a week for 4 weeks on the dominant leg. Participants in the control group were instructed not to do any stretching for 4 weeks. Pressure pain threshold (PPT) and temporal summation (TS) of pressure pain were measured on the stretched calf, the contra-lateral calf, and contra-lateral lower arm using a computerized cuff algometer. Analyses of variance on the per-protocol population (defined as participants that adhered to the protocol) were used to assess group differences in the changes from baseline. Forty healthy volunteers were included, of which 34 participants adhered to the protocol (15 intervention group/19 control group). No statistically significant group differences in the changes from baseline were found regarding PPT and TS measurements for the stretched calf, the contra-lateral calf, and the arm. Four weeks of regular stretching of the calf muscles does not affect pressure pain sensitivity, suggesting that pressure pain sensitivity is unaffected by stretching in a healthy population. The mechanisms underlying any benefits of regular stretching remain to be explained. © 2015 World Institute of Pain.

Fear-avoidance beliefs and temporal summation of evoked thermal pain influence self-report of disability in patients with chronic low back pain.

PubMed

George, Steven Z; Wittmer, Virgil T; Fillingim, Roger B; Robinson, Michael E

2006-03-01

Quantitative sensory testing has demonstrated a promising link between experimentally determined pain sensitivity and clinical pain. However, previous studies of quantitative sensory testing have not routinely considered the important influence of psychological factors on clinical pain. This study investigated whether measures of thermal pain sensitivity (temporal summation, first pulse response, and tolerance) contributed to clinical pain reports for patients with chronic low back pain, after controlling for depression or fear-avoidance beliefs about work. Consecutive patients (n=27) with chronic low back pain were recruited from an interdisciplinary pain rehabilitation program in Jacksonville, FL. Patients completed validated self-report questionnaires for depression, fear-avoidance beliefs, clinical pain intensity, and clinical pain related disability. Patients also underwent quantitative sensory testing from previously described protocols to determine thermal pain sensitivity (temporal summation, first pulse response, and tolerance). Hierarchical regression models investigated the contribution of depression and thermal pain sensitivity to clinical pain intensity, and fear-avoidance beliefs and thermal pain sensitivity to clinical pain related disability. None of the measures of thermal pain sensitivity contributed to clinical pain intensity after controlling for depression. Temporal summation of evoked thermal pain significantly contributed to clinical pain disability after controlling for fear-avoidance beliefs about work. Measures of thermal pain sensitivity did not contribute to pain intensity, after controlling for depression. Fear-avoidance beliefs about work and temporal summation of evoked thermal pain significantly influenced pain related disability. These factors should be considered as potential outcome predictors for patients with work-related low back pain. This study supported the neuromatrix theory of pain for patients with CLBP, as cognitive

Testicle pain

MedlinePlus

... Causes The testicles are very sensitive. Even a minor injury can cause pain. In some conditions, abdominal ... Non-urgent causes of testicle pain, such as minor injuries and fluid collection, can often be treated ...

Anatomical association between wrist extensor musculature and topographical pain sensitivity maps of the elbow area.

PubMed

Prados-Frutos, Juan Carlos; Ruiz-Ruiz, Beatriz; De-la-Llave-Rincón, Ana Isabel; Arendt-Nielsen, Lars; Madeleine, Pascal; Fernández-de-Las-Peñas, César

2012-06-01

High-density topographical sensitivity maps have been developed to visualize nonuniformity deep tissue pain sensitivity in, for example, lateral epicondylitis (LE). The aim of this cadaveric study was to determine the anatomical association between the topographical sensitivity maps over the elbow area and wrist extensor musculature. A topographical pressure sensitivity map consisting of 12 points forming a 3 × 4 matrix: 4 points in the superior part, 4 points in the middle, and 4 points in the lower part around the lateral epicondyle was marker on a 50-year embalmed cadaver. Color marker pins were inserted into each point. Pins were removed during the process of dissection, but the small holes created by their removal assured accurate relocation. Progressive dissection revealed that points 1 to 4 (superior line) were placed over the musculotendinous junction and belly of the extensor carpi radialis brevis (ECRB) muscle, points 6 to 8 (middle line) were placed over the musculotendinous junction and belly of the extensor digitorum communis muscle, and points 9 to 12 (inferior line) were located over the musculotendinous junction and belly of the extensor carpi ulnaris muscle. It was also observed that the superficial branch of the radial nerve runs between the belly of the ECRB and extensor digitorum communis muscles. This study confirmed that anatomical location previously assumed supporting the important wrist extensor muscles, particularly the ECRB, in patients with LE as depicted by pressure pain sensitivity maps. This study also suggests a potential role of the superficial branch of the radial nerve in LE. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

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 ...

Pain and motor control: From the laboratory to rehabilitation.

PubMed

Hodges, Paul W

2011-04-01

Movement is changed in pain and is the target of clinical interventions. Yet the understanding of the physiological basis for movement adaptation in pain remains limited. Contemporary theories are relatively simplistic and fall short of providing an explanation for the variety of permutations of changes in movement control identified in clinical and experimental contexts. The link between current theories and rehabilitation is weak at best. New theories are required that both account for the breadth of changes in motor control in pain and provide direction for development and refinement of clinical interventions. This paper describes an expanded theory of the motor adaptation to pain to address these two issues. The new theory, based on clinical and experimental data argues that: activity is redistributed within and between muscles rather than stereotypical inhibition or excitation of muscles; modifies the mechanical behaviour in a variable manner with the objective to "protect" the tissues from further pain or injury, or threatened pain or injury; involves changes at multiple levels of the motor system that may be complementary, additive or competitive; and has short-term benefit, but with potential long-term consequences due to factors such as increased load, decreased movement, and decreased variability. This expanded theory provides guidance for rehabilitation directed at alleviating a mechanical contribution to the recurrence and persistence of pain that must be balanced with other aspects of a multifaceted intervention that includes management of psychosocial aspects of the pain experience. Copyright © 2011 Elsevier Ltd. 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

Uncovering the influence of social skills and psychosociological factors on pain sensitivity using structural equation modeling.

PubMed

Tanaka, Yoichi; Nishi, Yuki; Nishi, Yuki; Osumi, Michihiro; Morioka, Shu

2017-01-01

Pain is a subjective emotional experience that is influenced by psychosociological factors such as social skills, which are defined as problem-solving abilities in social interactions. This study aimed to reveal the relationships among pain, social skills, and other psychosociological factors by using structural equation modeling. A total of 101 healthy volunteers (41 men and 60 women; mean age: 36.6±12.7 years) participated in this study. To evoke participants' sense of inner pain, we showed them images of painful scenes on a PC screen and asked them to evaluate the pain intensity by using the visual analog scale (VAS). We examined the correlation between social skills and VAS, constructed a hypothetical model based on results from previous studies and the current correlational analysis results, and verified the model's fit using structural equation modeling. We found significant positive correlations between VAS and total social skills values, as well as between VAS and the "start of relationships" subscales. Structural equation modeling revealed that the values for "start of relationships" had a direct effect on VAS values (path coefficient =0.32, p <0.01). In addition, the "start of relationships" had both a direct and an indirect effect on psychological factors via social support. The results indicated that extroverted people are more sensitive to inner pain and tend to get more social support and maintain a better psychological condition.

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.

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

Altering gender role expectations: effects on pain tolerance, pain threshold, and pain ratings.

PubMed

Robinson, Michael E; Gagnon, Christine M; Riley, Joseph L; Price, Donald D

2003-06-01

The literature demonstrating sex differences in pain is sizable. Most explanations for these differences have focused on biologic mechanisms, and only a few studies have examined social learning. The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain. This study used experimental manipulation of gender-role expectations for men and women. One hundred twenty students participated in the cold pressor task. Before the pain task, participants were given 1 of 3 instructional sets: no expectation, 30-second performance expectation, or a 90-second performance expectation. Pain ratings, threshold, and tolerance were recorded. Significant sex differences in the "no expectation" condition for pain tolerance (t = 2.32, df = 38, P <.05) and post-cold pressor pain ratings (t = 2.6, df = 37, P <.05) were found. Women had briefer tolerance times and higher post-cold pressor ratings than men. When given gender-specific tolerance expectations, men and women did not differ in their pain tolerance, pain threshold, or pain ratings. This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain.

Choosing the right laboratory: a review of clinical and forensic toxicology services for urine drug testing in pain management.

PubMed

Reisfield, Gary M; Goldberger, Bruce A; Bertholf, Roger L

2015-01-01

Urine drug testing (UDT) services are provided by a variety of clinical, forensic, and reference/specialty laboratories. These UDT services differ based on the principal activity of the laboratory. Clinical laboratories provide testing primarily focused on medical care (eg, emergency care, inpatients, and outpatient clinics), whereas forensic laboratories perform toxicology tests related to postmortem and criminal investigations, and drug-free workplace programs. Some laboratories now provide UDT specifically designed for monitoring patients on chronic opioid therapy. Accreditation programs for clinical laboratories have existed for nearly half a century, and a federal certification program for drug-testing laboratories was established in the 1980s. Standards of practice for forensic toxicology services other than workplace drug testing have been established in recent years. However, no accreditation program currently exists for UDT in pain management, and this review considers several aspects of laboratory accreditation and certification relevant to toxicology services, with the intention to provide guidance to clinicians in their selection of the appropriate laboratory for UDT surveillance of their patients on opioid therapy.

Pain and the ethics of pain management.

PubMed

Edwards, R B

1984-01-01

In this article I clarify the concepts of 'pain', 'suffering', 'pains of body', 'pains of soul'. I explore the relevance of an ethic to the clinical setting which gives patients a strong prima facie right to freedom from unnecessary and unwanted pain and which places upon medical professionals two concomitant moral obligations to patients. First, there is the duty not to inflict pain and suffering beyond what is necessary for effective diagnosis, treatment and research. Next, there is the duty to do all that can be done to relieve all the pain and suffering which can be alleviated. I develop in some detail that individuality of pain sensitivity must be taken into account in fulfilling these obligations. I explore the issue of the relevance of informed consent and the right to refuse treatment to the matter of pain relief. And I raise the question of what conditions, if any, should override the right to refuse treatment where pain relief is of paramount concern.

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.

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

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

The Cuernos del Paine mountains in Torres del Paine National Park in Chile, photographed during NASA's AirSAR 2004 campaign

NASA Image and Video Library

2004-03-11

The Cuernos del Paine mountains in Torres del Paine National Park in Chile, photographed during NASA's AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. Founded in 1959, Torres del Paine National Park encompasses 450,000 acres in the Patagonia region of Chile. This region is being studied by NASA using a DC-8 equipped with an Airborne Synthetic Aperture Radar (AirSAR) developed by scientists from NASA’s Jet Propulsion Laboratory. This is a very sensitive region that is important to scientists because the temperature has been consistently rising causing a subsequent melting of the region’s glaciers. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Uncovering the influence of social skills and psychosociological factors on pain sensitivity using structural equation modeling

PubMed Central

Tanaka, Yoichi; Nishi, Yuki; Nishi, Yuki; Osumi, Michihiro; Morioka, Shu

2017-01-01

Pain is a subjective emotional experience that is influenced by psychosociological factors such as social skills, which are defined as problem-solving abilities in social interactions. This study aimed to reveal the relationships among pain, social skills, and other psychosociological factors by using structural equation modeling. A total of 101 healthy volunteers (41 men and 60 women; mean age: 36.6±12.7 years) participated in this study. To evoke participants’ sense of inner pain, we showed them images of painful scenes on a PC screen and asked them to evaluate the pain intensity by using the visual analog scale (VAS). We examined the correlation between social skills and VAS, constructed a hypothetical model based on results from previous studies and the current correlational analysis results, and verified the model’s fit using structural equation modeling. We found significant positive correlations between VAS and total social skills values, as well as between VAS and the “start of relationships” subscales. Structural equation modeling revealed that the values for “start of relationships” had a direct effect on VAS values (path coefficient =0.32, p<0.01). In addition, the “start of relationships” had both a direct and an indirect effect on psychological factors via social support. The results indicated that extroverted people are more sensitive to inner pain and tend to get more social support and maintain a better psychological condition. PMID:28979161

[Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

PubMed

Yarushkina, N I; Filaretova, L P

2015-01-01

Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

Conditioned pain modulation: a predictor for development and treatment of neuropathic pain.

PubMed

Granovsky, Yelena

2013-09-01

Psychophysical evaluation of endogenous pain inhibition via conditioned pain modulation (CPM) represents a new generation of laboratory tests for pain assessment. In this review we discuss recent findings on CPM in neuropathic pain and refer to psychophysical, neurophysiological, and methodological aspects of its clinical implications. Typically, chronic neuropathic pain patients express less efficient CPM, to the extent that incidence of acquiring neuropathic pain (e.g. post-surgery) and its intensity can be predicted by a pre-surgery CPM assessment. Moreover, pre-treatment CPM evaluation may assist in the correct choice of serotonin-noradrenalin reuptake inhibitor analgesic agents for individual patients. Evaluation of pain modulation capabilities can serve as a step forward in individualizing pain medicine.

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

Sensitivity, specificity, and reproducibility of four measures of laboratory turnaround time.

PubMed

Valenstein, P N; Emancipator, K

1989-04-01

The authors studied the performance of four measures of laboratory turnaround time: the mean, median, 90th percentile, and proportion of tests reported within a predetermined cut-off interval (proportion of acceptable tests [PAT]). Measures were examined with the use of turnaround time data from 11,070 stat partial thromboplastin times, 16,761 urine cultures, and 28,055 stat electrolyte panels performed by a single laboratory. For laboratories with long turnaround times, the most important quality of a turnaround time measure is high reproducibility, so that improvement in reporting speed can be distinguished from random variation resulting from sampling. The mean was found to be the most reproducible of the four measures, followed by the median. The mean achieved acceptable precision with sample sizes of 100-500 tests. For laboratories with normally rapid turnaround times, the most important quality of a measure is high sensitivity and specificity for detecting whether turnaround time has dropped below standards. The PAT was found to be the best measure of turnaround time in this setting but required sample sizes of at least 500 tests to achieve acceptable accuracy. Laboratory turnaround time may be measured for different reasons. The method of measurement should be chosen with an eye toward its intended application.

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.

Lack of evidence for central sensitization in idiopathic, non-traumatic neck pain: a systematic review.

PubMed

Malfliet, Annaleen; Kregel, Jeroen; Cagnie, Barbara; Kuipers, Mandy; Dolphens, Mieke; Roussel, Nathalie; Meeus, Mira; Danneels, Lieven; Bramer, Wichor M; Nijs, Jo

2015-01-01

Chronic neck pain is a common problem with a poorly understood pathophysiology. Often no underlying structural pathology can be found and radiological imaging findings are more related to age than to a patient's symptoms. Besides its common occurrence, chronic idiopathic neck pain is also very disabling with almost 50% of all neck pain patients showing moderate disability at long-term follow-up. Central sensitization (CS) is defined as "an amplification of neural signaling within the central nervous system that elicits pain hypersensitivity," "increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input," or "an augmentation of responsiveness of central neurons to input from unimodal and polymodal receptors." There is increasing evidence for involvement of CS in many chronic pain conditions. Within the area of chronic idiopathic neck pain, there is consistent evidence for the presence and clinical importance of CS in patients with traumatic neck pain, or whiplash-associated disorders. However, the majority of chronic idiopathic neck pain patients are unrelated to a traumatic injury, and hence are termed chronic idiopathic non-traumatic neck pain. When comparing whiplash with idiopathic non-traumatic neck pain, indications for different underlying mechanisms are found. The goal of this article was to review the existing scientific literature on the role of CS in patients with chronic idiopathic non-traumatic neck pain. Systematic review. All selected studies were case control studies. A systematic search of existing, relevant literature was performed via the electronic databases Medline, Embase, Web of Science, Cinahl, PubMed, and Google Scholar. All titles and abstracts were checked to identify relevant articles. An article was considered eligible if it met following inclusion criteria: (1) participants had to be human adults (> 18 years) diagnosed with idiopathic non-traumatic chronic (present for at

Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization

PubMed Central

Costantini, Raffaele; Affaitati, Giannapia; Massimini, Francesca; Tana, Claudio; Innocenti, Paolo; Giamberardino, Maria Adele

2016-01-01

Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(p<0.0001). After cholecystectomy, fibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, p<0.01-p<0.001), the decrease in muscle thresholds correlating linearly with the peak postoperative pain at surgery site (p<0.003-p<0.0001). Fibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (p<0.05-p<0.0001). Over the same 12-month period: in non-fibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (p<0.05-p<0.0001). The results of the study show that biliary colics from

Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization.

PubMed

Costantini, Raffaele; Affaitati, Giannapia; Massimini, Francesca; Tana, Claudio; Innocenti, Paolo; Giamberardino, Maria Adele

2016-01-01

Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(p<0.0001). After cholecystectomy, fibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, p<0.01-p<0.001), the decrease in muscle thresholds correlating linearly with the peak postoperative pain at surgery site (p<0.003-p<0.0001). Fibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (p<0.05-p<0.0001). Over the same 12-month period: in non-fibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (p<0.05-p<0.0001). The results of the study show that biliary colics from

Profiling Arthritis Pain with a Decision Tree.

PubMed

Hung, Man; Bounsanga, Jerry; Liu, Fangzhou; Voss, Maren W

2018-06-01

Arthritis is the leading cause of work disability and contributes to lost productivity. Previous studies showed that various factors predict pain, but they were limited in sample size and scope from a data analytics perspective. The current study applied machine learning algorithms to identify predictors of pain associated with arthritis in a large national sample. Using data from the 2011 to 2012 Medical Expenditure Panel Survey, data mining was performed to develop algorithms to identify factors and patterns that contribute to risk of pain. The model incorporated over 200 variables within the algorithm development, including demographic data, medical claims, laboratory tests, patient-reported outcomes, and sociobehavioral characteristics. The developed algorithms to predict pain utilize variables readily available in patient medical records. Using the machine learning classification algorithm J48 with 50-fold cross-validations, we found that the model can significantly distinguish those with and without pain (c-statistics = 0.9108). The F measure was 0.856, accuracy rate was 85.68%, sensitivity was 0.862, specificity was 0.852, and precision was 0.849. Physical and mental function scores, the ability to climb stairs, and overall assessment of feeling were the most discriminative predictors from the 12 identified variables, predicting pain with 86% accuracy for individuals with arthritis. In this era of rapid expansion of big data application, the nature of healthcare research is moving from hypothesis-driven to data-driven solutions. The algorithms generated in this study offer new insights on individualized pain prediction, allowing the development of cost-effective care management programs for those experiencing arthritis pain. © 2017 World Institute of Pain.

Measuring pain in children with cognitive impairment: pain response to surgical procedures.

PubMed

Terstegen, Chantal; Koot, Hans M; de Boer, Josien B; Tibboel, Dick

2003-05-01

This study investigated post-surgical pain in children with profound cognitive impairment (PCI), searching for a core set of cues these children use to express their pain. Fifty-two children were observed while they were admitted to the Sophia Children's Hospital for surgery, twice before and five times after surgery. All observations were scored with the item pool consisting of 134 possible pain indicators, using a five-point scale ranging from 0 (never shown) to 4 (always shown). Second, we used the visual analogue scale (VAS) to give a general impression of the severity of the children's pain during the episodes they were observed. Several analyses provided evidence that 23 observable behaviors are sensitive to post-surgical pain in children with PCI, regardless of the pain intensity of the surgical procedures they underwent. The finding that all indicators, except for one, were scored significantly higher on episodes with VAS ratings >or=4, indicates the sensitivity of these indicators concerning absence versus presence of clinically meaningful levels of pain. This study reveals the potential clinical utility of a core set of indicators which can be used to assess post-surgical pain in children with PCI.

Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice.

PubMed

Miller, A L; Leach, M C

2015-04-01

Social housing is recommended where possible for laboratory mice. In order to achieve this, mice must be individually identifiable. Although, various methods are available, permanent identification is often required, such as ear notching. This method is likely to be painful and to date there is limited literature on pain assessment and alleviation for this routine husbandry practice. Here we aimed to determine if the mouse grimace scale (MGS) could be used to assess pain in C57BL/6 mice following routine ear notching. Langford et al. found that very acute noxious stimuli (i.e. < 10 min in duration) did not produce a change in MGS score in comparison to baseline. Here, no significant difference was found between MGS scores at baseline and immediately post ear notching, potentially indicating that the pain associated with ear notching is either too acute to assess using the MGS tool or the practice is not painful. Studies in other species indicate that ear notching is painful, therefore, unless we can confidently conclude that the process of ear notching is not painful, we should err on the side of caution and assume it is painful due to the large number of mice ear-notched and potential welfare consequences. Alternative methods of assessing pain following this routine practice should be used in order to assess both the potential pain in mice, and the effectiveness of analgesics or local anaesthetics to relieve any associated pain. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Pain and Laboratory Animals: Publication Practices for Better Data Reproducibility and Better Animal Welfare

PubMed Central

Carbone, Larry; Austin, Jamie

2016-01-01

Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful experiment. To explore how scientists in a range of fields describe their management of this ethical and methodological concern, we scored 400 scientific articles that included major animal survival surgeries as part of their experimental methods, for the completeness of information on anesthesia and analgesia. The 400 articles (250 accepted for publication pre-2011, and 150 in 2014–15, along with 174 articles they reference) included thoracotomies, craniotomies, gonadectomies, organ transplants, peripheral nerve injuries, spinal laminectomies and orthopedic procedures in dogs, primates, swine, mice, rats and other rodents. We scored articles for Publication Completeness (PC), which was any mention of use of anesthetics or analgesics; Analgesia Use (AU) which was any use of post-surgical analgesics, and Analgesia Completeness (a composite score comprising intra-operative analgesia, extended post-surgical analgesia, and use of multimodal analgesia). 338 of 400 articles were PC. 98 of these 338 were AU, with some mention of analgesia, while 240 of 338 mentioned anesthesia only but not post-surgical analgesia. Journals’ caliber, as measured by their 2013 Impact Factor, had no effect on PC or AU. We found no effect of whether a journal instructs authors to consult the ARRIVE publishing guidelines

Pain and Laboratory Animals: Publication Practices for Better Data Reproducibility and Better Animal Welfare.

PubMed

Carbone, Larry; Austin, Jamie

2016-01-01

Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful experiment. To explore how scientists in a range of fields describe their management of this ethical and methodological concern, we scored 400 scientific articles that included major animal survival surgeries as part of their experimental methods, for the completeness of information on anesthesia and analgesia. The 400 articles (250 accepted for publication pre-2011, and 150 in 2014-15, along with 174 articles they reference) included thoracotomies, craniotomies, gonadectomies, organ transplants, peripheral nerve injuries, spinal laminectomies and orthopedic procedures in dogs, primates, swine, mice, rats and other rodents. We scored articles for Publication Completeness (PC), which was any mention of use of anesthetics or analgesics; Analgesia Use (AU) which was any use of post-surgical analgesics, and Analgesia Completeness (a composite score comprising intra-operative analgesia, extended post-surgical analgesia, and use of multimodal analgesia). 338 of 400 articles were PC. 98 of these 338 were AU, with some mention of analgesia, while 240 of 338 mentioned anesthesia only but not post-surgical analgesia. Journals' caliber, as measured by their 2013 Impact Factor, had no effect on PC or AU. We found no effect of whether a journal instructs authors to consult the ARRIVE publishing guidelines

Impact of triphenyltin acetate in microcosms simulating floodplain lakes. II. Comparison of species sensitivity distributions between laboratory and semi-field.

PubMed

Roessink, I; Belgers, J D M; Crum, S J H; van den Brink, P J; Brock, T C M

2006-07-01

The study objectives were to shed light on the types of freshwater organism that are sensitive to triphenyltin acetate (TPT) and to compare the laboratory and microcosm sensitivities of the invertebrate community. The responses of a wide array of freshwater taxa (including invertebrates, phytoplankton and macrophytes) from acute laboratory Single Species Tests (SST) were compared with the concentration-response relationships of aquatic populations in two types of freshwater microcosms. Representatives of several taxonomic groups of invertebrates, and several phytoplankton and vascular plant species proved to be sensitive to TPT, illustrating its diverse modes of toxic action. Statistically calculated ecological risk thresholds (HC5 values) based on 96 h laboratory EC50 values for invertebrates were 1.3 microg/l, while these values on the basis of microcosm-Species Sensitivity Distributions (SSD) for invertebrates in sampling weeks 2-8 after TPT treatment ranged from 0.2 to 0.6 microg/l based on nominal peak concentrations. Responses observed in the microcosms did not differ between system types and sampling dates, indicating that ecological threshold levels are not affected by different community structures including taxa sensitive to TPT. The laboratory-derived invertebrate SSD curve was less sensitive than the curves from the microcosms. Possible explanations for the more sensitive field response are delayed effects and/or additional chronic exposure via the food chain in the microcosms.

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

Effect of individually tailored biopsychosocial workplace interventions on chronic musculoskeletal pain, stress and work ability among laboratory technicians: randomized controlled trial protocol.

PubMed

Jay, Kenneth; Brandt, Mikkel; Sundstrup, Emil; Schraefel, Mc; Jakobsen, Markus D; Sjøgaard, Gisela; Andersen, Lars L

2014-12-18

Among laboratory technicians, the prevalence of neck and shoulder pain is widespread possibly due to typical daily work tasks such as pipetting, preparing vial samples for analysis, and data processing on a computer including mouse work - all tasks that require precision in motor control and may result in extended periods of time spent in static positions.In populations characterized by intense chronic musculoskeletal pain and diagnosed conditions in conjunction with psycho-physiological symptoms such as stress-related pain and soreness and other disabling conditions, multifactorial approaches applying a combination of individually tailored physical and cognitive strategies targeting the areas most needed, may be an effective solution to the physical and mental health challenges.The aim of this study is therefore to investigate the effect of an individually tailored biopsychosocial intervention strategy on musculoskeletal pain, stress and work disability in lab technicians with a history of musculoskeletal pain at a single worksite in Denmark. In this single-blind two-armed parallel-group randomized controlled trial with allocation concealment, participants receive either an individualized multifactorial intervention or "usual care" for 10 weeks at the worksite. 1) female laboratory technician (18-67 years of age) and 2) Pain intensity ≥ 3 (0-10 Visual Analogue Scale) lasting ≥3 months with a frequency of ≥ 3 days per week in one or more of the following regions: i) upper back i) low back iii) neck, iv) shoulder, v) elbow and/or vi) hand. 1) life-threatening disease and 2) pregnancy. Stress, as measured by Cohen´s perceived stress questionnaire is not an inclusion criteria, thus participants can participate regardless of their stress level.We will implement an individualized intervention addressing biopsychosocial elements of musculoskeletal pain with the following components; i) increasing physical capacity through strength- and motor control

Biological sex and social setting affects pain intensity and observational coding of other people's pain behaviors.

PubMed

Vigil, Jacob M; Coulombe, Patrick

2011-09-01

This experiment examines the impact of biological sex and audience composition on laboratory-induced ischemic pain intensity and observational coding of other people's pain behaviors. Situational context was manipulated by varying the sex and number of audience stimuli in the laboratory setting during the pain task and during observational evaluations of other people's pain suffering. The analyses revealed sex differences in felt pain intensity and observable pain behaviors, with male subjects reporting lower pain intensity and evidencing fewer pain behaviors than female subjects on average. Follow-up analyses revealed that, after controlling for social anxiety, audience composition was linked to felt pain intensity, and this relation was moderated by participant sex and audience sex, such that only male subjects showed decreased pain intensity with increasing number of female audience members. Sex differences were also found in the rating of other people's pain behaviors, with male observers rating the pain of others lower than female observers. Composition of the audience influenced observers' pain ratings such that the presence of more male subjects in the audience correlated with lower observer ratings, whereas the presence of more female subjects correlated with higher observer ratings. This is the first study to show that the sex and the composition of the social context in which pain is experienced affects the intensity of felt pain and the evaluation of other people's pain suffering. Implications of the findings for measuring and interpreting pain suffering in male and female patients by male and female treatment providers in health care settings are discussed. Published by Elsevier B.V.

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

Neurophysiology of pain and hypnosis for chronic pain.

PubMed

Dillworth, Tiara; Mendoza, M Elena; Jensen, Mark P

2012-03-01

In the past decade there has been a dramatic increase in (1) understanding the neurophysiological components of the pain experiences, (2) randomized clinical trials testing the efficacy of hypnotic treatments on chronic pain, and (3) laboratory research examining the effects of hypnosis on the neurophysiological processes implicated in pain. Work done in these areas has not only demonstrated the efficacy of hypnosis for treating chronic pain but is beginning to shed light on neurophysiological processes that may play a role in its effectiveness. This paper reviews a selection of published studies from these areas of research, focusing on recent findings that have the most potential to inform both clinical work and research in this area. The paper concludes with research and clinical recommendations for maximizing treatment efficacy based on the research findings that are available.

Prevention and reversal of latent sensitization of dorsal horn neurons by glial blockers in a model of low back pain in male rats.

PubMed

Zhang, Juanjuan; Mense, Siegfried; Treede, Rolf-Detlef; Hoheisel, Ulrich

2017-10-01

In an animal model of nonspecific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues. To block microglial activation, minocycline was continuously administered intrathecally starting 1 day before or 2 days after the first NGF injection. The glia inhibitor fluorocitrate that also blocks astrocyte activation was administrated 2 days after the first injection. Minocycline applied before the first NGF injection reduced the manifest sensitization after the second NGF injection to control values. The proportion of neurons responsive to stimulation of deep tissues was reduced from 50% to 17.7% ( P < 0.01). No significant changes occurred when minocycline was applied after the first injection. In contrast, fluorocitrate administrated after the first NGF injection reduced significantly the proportion of neurons with deep input (15.8%, P < 0.01). A block of glia activation had no significant effect on the increased resting activity. The data suggest that blocking microglial activation prevented the NGF-induced latent spinal sensitization, whereas blocking astrocyte activation reversed it. The induction of spinal neuronal sensitization in this pain model appears to depend on microglia activation, whereas its maintenance is regulated by activated astrocytes. NEW & NOTEWORTHY Activated microglia and astrocytes mediate the latent sensitization induced by nerve growth factor in dorsal horn neurons that receive input from deep tissues of the low back. These processes may contribute to nonspecific low back pain. Copyright © 2017 the

Impaired conditioned pain modulation in youth with functional abdominal pain

PubMed Central

Morris, Matthew C.; Walker, Lynn S.; Bruehl, Stephen; Stone, Amanda L.; Mielock, Alyssa S.; Rao, Uma

2016-01-01

Functional abdominal pain (FAP) is associated with enhanced pain responsiveness. Although impaired conditioned pain modulation (CPM) characterizes adults with a variety of chronic pain conditions, relatively little is known about CPM in youth with FAP. The present study assessed CPM to evoked thermal pain in 140 youth (ages 10 to 17), 63 of whom had FAP and 77 of whom were healthy controls. Multilevel models demonstrated weaker CPM effects in FAP than healthy youth, as evident in slower within-person decreases in pain ratings during the conditioning phase. Weaker CPM effects were associated with greater somatic symptom severity and functional disability. Pain responses in FAP youth were heterogeneous, with 43% of youth showing an unexpected increase in pain ratings during the conditioning phase, suggesting sensitization rather than CPM-related pain inhibition. These findings highlight directions for future research on the emergence and maintenance of FAP in youth. PMID:27389918

Impaired conditioned pain modulation in youth with functional abdominal pain.

PubMed

Morris, Matthew C; Walker, Lynn S; Bruehl, Stephen; Stone, Amanda L; Mielock, Alyssa S; Rao, Uma

2016-10-01

Functional abdominal pain (FAP) is associated with enhanced pain responsiveness. Although impaired conditioned pain modulation (CPM) characterizes adults with a variety of chronic pain conditions, relatively little is known about CPM in youth with FAP. This study assessed CPM to evoked thermal pain in 140 youth (ages 10-17), 63 of whom had FAP and 77 of whom were healthy controls. Multilevel models demonstrated weaker CPM effects in youth with FAP than in healthy youth, as evident in slower within-person decreases in pain ratings during the conditioning phase. Weaker CPM effects were associated with greater somatic symptom severity and functional disability. Pain responses in youth with FAP were heterogeneous, with 43% of youth showing an unexpected increase in pain ratings during the conditioning phase, suggesting sensitization rather than CPM-related pain inhibition. These findings highlight directions for future research on the emergence and maintenance of FAP in youth.

McMaster-Toronto Arthritis Patient Preference Disability Questionnaire Sensitivity to Change in Low Back Pain: Influence of Shifts in Priorities

PubMed Central

Sanchez, Katherine; Papelard, Agathe; Nguyen, Christelle; Bendeddouche, Imad; Jousse, Marylène; Rannou, François; Revel, Michel; Poiraudeau, Serge

2011-01-01

Objective To assess the sensitivity to change of the McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR) in chronic low back pain (CLBP) and shifts in patients' priorities of disabling activities over time. Methods A prospective longitudinal survey of 100 patients (38 males) with CLBP in a tertiary care teaching hospital. Evaluation at baseline and 6 months by the MACTAR, Quebec Back Pain Disability Questionnaire (QUEBEC), Hospital Anxiety and Depression scale (HAD), Fear-Avoidance Beliefs Questionnaire (FABQ), Coping Strategies Questionnaire (CSQ), and pain and handicap visual analogue scales (VASs). Patients' perceived improvement or worsening of condition was assessed at 6 months. Effect size (ES) and Standardized response mean (SRM) and effect size (ES) were used to evaluate sensitivity to change of the MACTAR. Results The MACTAR SRM and ES values (SRM = 0.25; ES = 0.37) were among the highest for the instruments evaluated. For patients considering their condition as improved, the SRM was 0.66 and the ES 1. The 3 disability domains, classified by the International Classification of Functioning, Disability and Health (ICF), most often cited as priorities at baseline remained the most cited at follow-up: mobility (40.9% of patients); community, social and civic life (22.7%); and domestic life (22.4%). At 6 months, 48 patients shifted their priorities, for a decrease in MACTAR SRM and ES values for patients considering their condition improved and an increase in these values for those considering their condition deteriorated. Conclusions Although the MACTAR has similar sensitivity to change as other outcome measures widely used in CLBP, shifts in patient priorities over time are common and influence scores and sensitivity to change. PMID:21629777

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®

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

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

The Negative Affect Hypothesis of Noise Sensitivity

PubMed Central

Shepherd, Daniel; Heinonen-Guzejev, Marja; Heikkilä, Kauko; Dirks, Kim N.; Hautus, Michael J.; Welch, David; McBride, David

2015-01-01

Some studies indicate that noise sensitivity is explained by negative affect, a dispositional tendency to negatively evaluate situations and the self. Individuals high in such traits may report a greater sensitivity to other sensory stimuli, such as smell, bright light and pain. However, research investigating the relationship between noise sensitivity and sensitivity to stimuli associated with other sensory modalities has not always supported the notion of a common underlying trait, such as negative affect, driving them. Additionally, other explanations of noise sensitivity based on cognitive processes have existed in the clinical literature for over 50 years. Here, we report on secondary analyses of pre-existing laboratory (n = 74) and epidemiological (n = 1005) data focusing on the relationship between noise sensitivity to and annoyance with a variety of olfactory-related stimuli. In the first study a correlational design examined the relationships between noise sensitivity, noise annoyance, and perceptual ratings of 16 odors. The second study sought differences between mean noise and air pollution annoyance scores across noise sensitivity categories. Results from both analyses failed to support the notion that, by itself, negative affectivity explains sensitivity to noise. PMID:25993104

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.

Effect of short-term cold-water immersion on muscle pain sensitivity in elite track cyclists.

PubMed

Klich, Sebastian; Krymski, Igor; Michalik, Kamil; Kawczyński, Adam

2018-05-01

To determine the effect of short-term cold-water immersion (CWI) on muscle pain sensitivity after maximal anaerobic power training in track cyclists. Repeated measures. University Laboratory. 12 elite sprint track cyclists (age 24,75 ± 4,23 years). PPT measurements were made on dominant lower extremity (right) in 20 reference points, including anterior thigh muscles, posterior thigh muscles and posterior cuff muscles. PPT levels were measured: 1) before workout, 2) immediately after workout, but before CWI 3) 1 h after CWI and 4) 12 h after CWI. Mean PPT values for each muscle group per participant were calculated for further statistical analysis. The average PPT for anterior thigh muscles decreased significantly after effort (p = 0.001) and increased significantly 1 h after CWI (p = 0.048). In posterior thigh muscles PPT decreased significantly after effort (p = 0.014) and increased significantly 1 h and 12 h after CWI (p = 0.045 and p = 0.25 respectively). However, in posterior cuff muscles PPT decreased only after effort (p = 0.001). Short-term repeated sprint exercise appears to affect PPT in track cyclists. This study have reported that CWI in 5 °C for 5 min have had a beneficial effect in minimizing PPT 1 h post repeated maximal sprint training. Copyright © 2018 Elsevier Ltd. All rights reserved.

[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.

Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

PubMed

Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

2015-04-01

Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Painful purinergic receptors.

PubMed

Donnelly-Roberts, Diana; McGaraughty, Steve; Shieh, Char-Chang; Honore, Prisca; Jarvis, Michael F

2008-02-01

Multiple P2 receptor-mediated mechanisms exist by which ATP can alter nociceptive sensitivity following tissue injury. Evidence from a variety of experimental strategies, including genetic disruption studies and the development of selective antagonists, has indicated that the activation of P2X receptor subtypes, including P2X(3), P2X(2/3), P2X(4) and P2X(7), and P2Y (e.g., P2Y(2)) receptors, can modulate pain. For example, administration of a selective P2X(3) antagonist, A-317491, has been shown to effectively block both hyperalgesia and allodynia in different animal models of pathological pain. Intrathecally delivered antisense oligonucleotides targeting P2X(4) receptors decrease tactile allodynia following nerve injury. Selective antagonists for the P2X(7) receptor also reduce sensitization in animal models of inflammatory and neuropathic pain, providing evidence that purinergic glial-neural interactions are important modulators of noxious sensory neurotransmission. Furthermore, activation of P2Y(2) receptors leads to sensitization of polymodal transient receptor potential-1 receptors. Thus, ATP acting at multiple purinergic receptors, either directly on neurons (e.g., P2X(3), P2X(2/3), and P2Y receptors) or indirectly through neural-glial cell interactions (P2X(4) and P2X(7) receptors), alters nociceptive sensitivity. The development of selective antagonists for some of these P2 receptors has greatly aided investigations into the nociceptive role of ATP. This perspective highlights some of the recent advances to identify selective P2 receptor ligands, which has enhanced the investigation of ATP-related modulation of pain sensitivity.

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.

Sensitivity studies and laboratory measurements for the laser heterodyne spectrometer experiment

NASA Technical Reports Server (NTRS)

Allario, F.; Katzberg, S. J.; Larsen, J. C.

1980-01-01

Several experiments involving spectral scanning interferometers and gas filter correlation radiometers (ref. 2) using limb scanning solar occultation techniques under development for measurements of stratospheric trace gases from Spacelab and satellite platforms are described. An experiment to measure stratospheric trace constituents by Laser Heterodyne Spectroscopy, a summary of sensitivity analyses, and supporting laboratory measurements are presented for O3, ClO, and H2O2 in which the instrument transfer function is modeled using a detailed optical receiver design.

Immediate effects of atlanto-occipital joint manipulation on active mouth opening and pressure pain sensitivity in women with mechanical neck pain.

PubMed

Mansilla-Ferragut, Pilar; Fernández-de-Las Peñas, César; Alburquerque-Sendín, Francisco; Cleland, Joshua A; Boscá-Gandía, Juan José

2009-02-01

The purpose of this study was to investigate the effects of a spinal thrust manipulation directed to the upper cervical segments (atlanto-occipital joint) on active mouth opening and pressure pain sensitivity in a trigeminal nerve innervated region (sphenoid bone) in women with mechanical neck pain. Thirty-seven women, ages 21 to 50 years old (mean age, 35 +/- 8 years) with mechanical neck pain were recruited for this study. Participants were randomly assigned into 1 of 2 groups as follows: an experimental group that received a spinal manipulation of the atlanto-occipital joint and a control group that received a manual contact placebo intervention. Outcomes collected were assessed pretreatment and 5 minutes posttreatment by an assessor blinded to the treatment allocation and included active mouth opening and pressure pain thresholds (PPTs) over both sides of the sphenoid bone. A 2-way repeated measures analysis of variance (ANOVA) with time (pre-post) as the within subjects variable and group (control, experimental) as the between subjects variable was used to examine the effects of the intervention. The hypothesis of interest was group-time interaction. The ANOVA showed a significant effect for time (F = 23.1; P < .001) and an interaction between group and time (F = 37.7; P < .001) for active mouth opening as follows: the experimental group showed a greater improvement when compared to the control group. A large positive within-group effect size (d > 1.5) for the experimental group, whereas a negative medium within-group effect size (d = -0.5) for the control group were identified. The ANOVA showed a significant interaction between group and time (F = 14.4; P < .001) for PPT levels at the sphenoid bone as follows: the experimental group showed a greater improvement when compared to the control group. A medium positive within-group effect size (d = -0.5) for the experimental group, whereas a negative medium within-group effect size (d = -0.5) for the control group

Lumbar Disc Screening Using Back Pain Questionnaires: Oswestry Low Back Pain Score, Aberdeen Low Back Pain Scale, and Acute Low Back Pain Screening Questionnaire

PubMed Central

Kim, Do Yeon; Oh, Chang Hyun; Park, Hyung Chun; Park, Chong Oon

2012-01-01

Objective To evaluate the usefulness of back pain questionnaires for lumbar disc screening among Korean young males. Methods We carried out a survey for lumbar disc screening through back pain questionnaires among the volunteers with or without back pain. Three types of back pain questionnaire (Oswestry Low Back Pain Score, Aberdeen Low Back Pain Scale, and Acute Low Back Pain Screeing Questionnaire) were randomly assigned to the examinees. The authors reviewed lumbar imaging studies (simple lumbar radiographs, lumbar computed tomography, and magnetic resolutional images), and the severity of lumbar disc herniation was categorized according to the guidelines issued by the Korean military directorate. We calculated the relationship between the back pain questionnaire scores and the severity of lumbar disc herniation. Results The scores of back pain questionnaires increased according to the severity of lumbar disc herniation. But, the range of scores was very vague, so it is less predictable to detect lumbar disc herniation using only back pain questionnaires. The sensitivity between the back pain questionnaires and the presence of lumbar disc herniation was low (16-64%). Conclusion Screening of lumbar disc herniation using only back pain questionnaires has limited value. PMID:25983807

Active pain coping is associated with the response in real-time fMRI neurofeedback during pain.

PubMed

Emmert, Kirsten; Breimhorst, Markus; Bauermann, Thomas; Birklein, Frank; Rebhorn, Cora; Van De Ville, Dimitri; Haller, Sven

2017-06-01

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback is used as a tool to gain voluntary control of activity in various brain regions. Little emphasis has been put on the influence of cognitive and personality traits on neurofeedback efficacy and baseline activity. Here, we assessed the effect of individual pain coping on rt-fMRI neurofeedback during heat-induced pain. Twenty-eight healthy subjects completed the Coping Strategies Questionnaire (CSQ) prior to scanning. The first part of the fMRI experiment identified target regions using painful heat stimulation. Then, subjects were asked to down-regulate the pain target brain region during four neurofeedback runs with painful heat stimulation. Functional MRI analysis included correlation analysis between fMRI activation and pain ratings as well as CSQ ratings. At the behavioral level, the active pain coping (first principal component of CSQ) was correlated with pain ratings during neurofeedback. Concerning neuroimaging, pain sensitive regions were negatively correlated with pain coping. During neurofeedback, the pain coping was positively correlated with activation in the anterior cingulate cortex, prefrontal cortex, hippocampus and visual cortex. Thermode temperature was negatively correlated with anterior insula and dorsolateral prefrontal cortex activation. In conclusion, self-reported pain coping mechanisms and pain sensitivity are a source of variance during rt-fMRI neurofeedback possibly explaining variations in regulation success. In particular, active coping seems to be associated with successful pain regulation.

Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.

PubMed

Lautenbacher, Stefan; Kunz, Miriam; Strate, Peter; Nielsen, Jesper; Arendt-Nielsen, Lars

2005-06-01

Experimental data on age-related changes in pain perception have so far been contradictory. It has appeared that the type of pain induction method is critical in this context, with sensitivity to heat pain being decreased whereas sensitivity to pressure pain may be even enhanced in the elderly. Furthermore, it has been shown that temporal summation of heat pain is more pronounced in the elderly but it has remained unclear whether age differences in temporal summation are also evident when using other pain induction methods. No studies on age-related changes in spatial summation of pain have so far been conducted. The aim of the present study was to provide a comprehensive survey on age-related changes in pain perception, i.e. in somatosensory thresholds (warmth, cold, vibration), pain thresholds (heat, pressure) and spatial and temporal summation of heat and pressure pain. We investigated 20 young (mean age 27.1 years) and 20 elderly (mean age 71.6 years) subjects. Our results confirmed and extended previous findings by showing that somatosensory thresholds for non-noxious stimuli increase with age whereas pressure pain thresholds decrease and heat pain thresholds show no age-related changes. Apart from an enhanced temporal summation of heat pain, pain summation was not found to be critically affected by age. The results of the present study provide evidence for stimulus-specific changes in pain perception in the elderly, with deep tissue (muscle) nociception being affected differently by age than superficial tissue (skin) nociception. Summation mechanisms contribute only moderately to age changes in pain perception.

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

Sex, Gender, and Pain: A Review of Recent Clinical and Experimental Findings

PubMed Central

Fillingim, Roger B.; King, Christopher D.; Ribeiro-Dasilva, Margarete C.; Rahim-Williams, Bridgett; Riley, Joseph L.

2009-01-01

Sex-related influences on pain and analgesia have become a topic of tremendous scientific and clinical interest, especially in the last 10 to 15 years. Members of our research group published reviews of this literature more than a decade ago, and the intervening time period has witnessed robust growth in research regarding sex, gender, and pain. Therefore, it seems timely to revisit this literature. Abundant evidence from recent epidemiologic studies clearly demonstrates that women are at substantially greater risk for many clinical pain conditions, and there is some suggestion that postoperative and procedural pain may be more severe among women than men. Consistent with our previous reviews, current human findings regarding sex differences in experimental pain indicate greater pain sensitivity among females compared with males for most pain modalities, including more recently implemented clinically relevant pain models such as temporal summation of pain and intramuscular injection of algesic substances. The evidence regarding sex differences in laboratory measures of endogenous pain modulation is mixed, as are findings from studies using functional brain imaging to ascertain sex differences in pain-related cerebral activation. Also inconsistent are findings regarding sex differences in responses to pharmacologic and non-pharmacologic pain treatments. The article concludes with a discussion of potential biopsychosocial mechanisms that may underlie sex differences in pain, and considerations for future research are discussed. Perspective This article reviews the recent literature regarding sex, gender, and pain. The growing body of evidence that has accumulated in the past 10 to 15 years continues to indicate substantial sex differences in clinical and experimental pain responses, and some evidence suggests that pain treatment responses may differ for women versus men. PMID:19411059

Production of consistent pain by intermittent infusion of sterile 5% hypertonic saline, followed by decrease of pain with cryotherapy.

PubMed

Long, Blaine C; Knight, Kenneth L; Hopkins, Ty; Parcell, Allen C; Feland, J Brent

2012-08-01

It is suggested that postinjury pain is difficult to examine; thus, investigators have developed experimental pain models. To minimize pain, cryotherapy (cryo) is applied, but reports on its effectiveness are limited. To investigate a pain model for the anterior knee and examine cryo in reducing the pain. Controlled laboratory study. Therapeutic modality laboratory. 30 physically active healthy male subjects who were free from any lower extremity orthopedic, neurological, cardiovascular, or endocrine pathologies. Perceived pain was measured every minute. Surface temperature was also assessed in the center of the patella and the popliteal fossa. There was a significant interaction between group and time (F68,864 = 3.0, P = .0001). At the first minute, there was no difference in pain between the 3 groups (saline/cryo = 4.80 ± 4.87 mm, saline/sham = 2.80 ± 3.55 mm, no saline/cryo = 4.00 ± 3.33 mm). During the first 5 min, pain increased from 4.80 ± 4.87 to 45.90 ± 21.17 mm in the saline/cryo group and from 2.80 ± 3.55 to 31.10 ± 20.25 mm in the saline/sham group. Pain did not change within the no-saline/cryo group, 4.00 ± 3.33 to 1.70 ± 1.70 mm. Pain for the saline/sham group remained constant for 17 min. Cryo decreased pain for 16 min in the saline/cryo group. There was no difference in preapplication surface temperature between or within each group. No change in temperature occurred within the saline/sham. Cooling and rewarming were similar in both cryo groups. Ambient temperature fluctuated less than 1°C during data collection. Intermittent infusion of sterile 5% hypertonic saline may be a useful experimental pain model in establishing a constant level of pain in a controlled laboratory setting. Cryotherapy decreased the induced anterior knee pain for 16 min.

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-01-01

Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PMID:27286745

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

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.

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

Pain vulnerability and DNA methyltransferase 3a involved in the affective dimension of chronic pain

PubMed Central

Wang, Wei; Li, Caiyue; Cai, Youqing; Pan, Zhizhong Z

2017-01-01

Chronic pain with comorbid emotional disorders is a prevalent neurological disease in patients under various pathological conditions, yet patients show considerable difference in their vulnerability to developing chronic pain. Understanding the neurobiological basis underlying this pain vulnerability is essential to develop targeted therapies of higher efficiency in pain treatment of precision medicine. However, this pain vulnerability has not been addressed in preclinical pain research in animals to date. In this study, we investigated individual variance in both sensory and affective/emotional dimensions of pain behaviors in response to chronic neuropathic pain condition in a mouse model of chronic pain. We found that mice displayed considerably diverse sensitivities in the chronic pain-induced anxiety- and depression-like behaviors of affective pain. Importantly, the mouse group that was more vulnerable to developing anxiety was also more vulnerable to developing depressive behavior under the chronic pain condition. In contrast, there was relatively much less variance in individual responses in the sensory dimension of pain sensitization. Molecular analysis revealed that those mice vulnerable to developing the emotional disorders showed a significant reduction in the protein level of DNA methyltransferase 3a in the emotion-processing central nucleus of the amygdala. In addition, social stress also revealed significant individual variance in anxiety behavior in mice. These findings suggest that individual pain vulnerability may be inherent mostly in the emotional/affective component of chronic pain and remain consistent in different aspects of negative emotion, in which adaptive changes in the function of DNA methyltransferase 3a for DNA methylation in central amygdala may play an important role. This may open a new avenue of basic research into the neurobiological mechanisms underlying pain vulnerability. PMID:28849714

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.

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

The Cuernos del Paine mountains in Torres del Paine National Park in Chile provide a backdrop to a herd of guanacos during NASA's AirSAR 2004 campaign

NASA Image and Video Library

2004-03-11

The Cuernos del Paine mountains in Torres del Paine National Park in Chile provide a backdrop to a herd of guanacos during NASA's AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. Founded in 1959, Torres del Paine National Park encompasses 450,000 acres in the Patagonia region of Chile. This region is being studied by NASA using a DC-8 equipped with an Airborne Synthetic Aperture Radar (AirSAR) developed by scientists from NASA’s Jet Propulsion Laboratory. This is a very sensitive region that is important to scientists because the temperature has been consistently rising causing a subsequent melting of the region’s glaciers. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Context sensitive regulation of pain and emotion: Development and initial validation of a scale for context insensitive avoidance.

PubMed

Flink, Ida K; Klein-Strandberg, Ester; Linton, Steven J

2017-10-01

Context insensitivity has been put forward as a potential mechanism explaining the high co-occurrence of pain and emotional distress. In the pain literature, the concept has only been introduced at a theoretical level and an assessment tool for exploring its impact is lacking. In an interpersonal setting, a core aspect of context sensitivity and insensitivity concerns when to disclose and when to avoid expressing pain and related distress. Both context insensitive disclosure and context insensitive avoidance may hamper interpersonal support and fuel the problem. This exploratory study describes an attempt to develop a self-report instrument to assess tendencies to disclose vs. avoid expressions of pain and related distress, as well as self-perceived adjustment of disclosure vs. avoidance to the context. A pool of items was systematically developed to assess different aspects of context insensitivity, including disclosure vs. avoidance of expression. 105 participants with persistent pain were recruited at pain rehabilitation clinics (80% of the sample) and in a university setting (20% of the sample). The participants responded to the pool of items as well as to a number of validated self-report instruments covering pain, pain-related disability, pain catastrophizing, emotion regulation tendencies, self-compassion and pain acceptance. The analyses explored the factorial structure of the initial instrument, as well as the criterion and construct validity. The analyses confirmed a stable underlying structure of the initial scale, with four distinct factors explaining 64.4% of the total variance. However, the criterion and construct validity could only be confirmed for one of the factors, which contained items reflecting context insensitive avoidance of expression. Consequently, only this factor, demonstrating very good internal consistency, was kept in the final version of the instrument which was named context insensitive avoidance (CIA). We found support for the

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

Pain perception studies in tension-type headache.

PubMed

Bezov, David; Ashina, Sait; Jensen, Rigmor; Bendtsen, Lars

2011-02-01

Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders. © 2010 American Headache Society.

The Role of Coping and Race in Healthy Children’s Experimental Pain Responses

PubMed Central

Evans, Subhadra; Lu, Qian; Tsao, Jennie C. I.; Zelter, Lonnie K.

2009-01-01

This study examined the relationship between race, laboratory-based coping strategies and anticipatory anxiety and pain intensity for cold, thermal (heat) and pressure experimental pain tasks. Participants were 123 healthy children and adolescents, including 33 African Americans (51% female; mean age =13.9 years) and 90 Caucasians (50% female; mean age = 12.6 years). Coping in response to the cold task was assessed with the Lab Coping Style interview; based on their interview responses, participants were categorized as ‘attenders’ (i.e., those who focused on the task) vs. ‘distractors’ (i.e., those who distracted themselves during the task). Analysis of covariance (ANCOVA) revealed significant interactions between race (African-American vs. Caucasian) and lab-based coping style after controlling for sex, age and socioeconomic status. African-American children classified as attenders reported less anticipatory anxiety for the cold task and lower pain intensity for the cold, heat and pressure tasks compared to those categorized as distractors. For these pain outcomes, Caucasian children classified as distractors reported less anticipatory anxiety and lower pain intensity relative to those categorized as attenders. The findings point to the moderating effect of coping in the relationship between race and experimental pain sensitivity. PMID:20352035

Growing Pains

PubMed Central

Lehman, Patrick J.; Carl, Rebecca L.

2017-01-01

Context: The term growing pains describes a common, benign syndrome of recurrent discomfort that occurs in young children. First described in the 1800s, the etiology of this condition remains unclear. The peak incidence does not correspond to a time of rapid growth. Children typically report bilateral pain in the lower extremities that occurs late in the day or at night. Evidence Acquisition: The PubMed database was searched using the keywords growing pains, benign nocturnal limb pains of childhood, recurrent limb pain of childhood, and limb pain in childhood. Articles were also found by reviewing references from the initial PubMed search. Only English-language articles published from 1900 through 2016 were included in the review. Study Design: Clinical review. Level of Evidence: Level 3. Results: When a patient’s history is classic for growing pains and physical examination is normal, laboratory and radiographic evaluation are not needed to make the diagnosis. Findings typical for growing pains include bilateral lower extremity pain usually experienced in the early evening or at night. The pain is not caused by activity and will not cause a limp. Conclusion: Additional workup is warranted for children with an atypical history, systemic symptoms, or for those individuals with physical examination abnormalities such as allodynia, focal tenderness, joint swelling, or decreased joint range of motion. Management of growing pains generally consists of symptomatic care with massage and over-the-counter analgesics, as well as reassurance to children and parents about the benign, self-limited nature of this condition. This review article summarizes data on the epidemiology, etiology, and management of growing pains and provides a framework for distinguishing this entity from other causes of extremity pain. PMID:28177851

Predictors of Abdominal Pain in Depressed Pediatric Inflammatory Bowel Disease Patients

PubMed Central

Srinath, Arvind I.; Goyal, Alka; Zimmerman, Lori A.; Newara, Melissa C.; Kirshner, Margaret A.; McCarthy, F. Nicole; Keljo, David; Binion, David; Bousvaros, Athos; DeMaso, David R.; Youk, Ada; Szigethy, Eva M.

2015-01-01

Background Pediatric patients with inflammatory bowel disease (IBD) have high rates of abdominal pain. The study aims were to (1) Evaluate biological and psychological correlates of abdominal pain in depressed youth with IBD, (2) Determine predictors of abdominal pain in Crohn’s disease (CD) and ulcerative colitis (UC). Methods 765 patients ages 9–17 with IBD seen over 3 years at two sites were screened for depression. Depressed youth completed comprehensive assessments for abdominal pain, psychological (depression and anxiety), and biological (IBD-related, through disease activity indices and laboratory values) realms. Results 217 patients with IBD (161 CD, 56 UC) were depressed. 163 (120 CD, 43 UC) patients had complete API scores. In CD, abdominal pain was associated with depression (r=0.33; p<0.001), diarrhea (r=0.34; p=0.001), ESR (r=0.22; p=0.02), low albumin (r=0.24; p=.01), weight loss (r=0.33; p=0.001), and abdominal tenderness (r=0.38, p=0.002). A multivariate model with these significant correlates represented 32% of the variance in pain. Only depression (p=0.03), weight loss (p=0.04), and abdominal tenderness (p=0.01) predicted pain for CD patients. In UC, pain was associated with depression (r=0.46; p=0.002) and nocturnal stools (r=.32; p=.046). In the multivariate model with these significant correlates 23% of the variance was explained, and only depression (p=0.02) predicted pain. Conclusions The psychological state of pediatric patients with IBD may increase the sensitivity to abdominal pain. Thus, screening for and treating comorbid depression may prevent excessive medical testing and unnecessary escalation of IBD medications. PMID:24983975

The sensitivity of laboratory tests assessing driving related skills to dose-related impairment of alcohol: A literature review.

PubMed

Jongen, S; Vuurman, E F P M; Ramaekers, J G; Vermeeren, A

2016-04-01

Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multiple active myofascial trigger points and pressure pain sensitivity maps in the temporalis muscle are related in women with chronic tension type headache.

PubMed

Fernández-de-las-Peñas, César; Caminero, Ana B; Madeleine, Pascal; Guillem-Mesado, Amparo; Ge, Hong-You; Arendt-Nielsen, Lars; Pareja, Juan A

2009-01-01

To describe the common locations of active trigger points (TrPs) in the temporalis muscle and their referred pain patterns in chronic tension type headache (CTTH), and to determine if pressure sensitivity maps of this muscle can be used to describe the spatial distribution of active TrPs. Forty women with CTTH were included. An electronic pressure algometer was used to assess pressure pain thresholds (PPT) from 9 points over each temporalis muscle: 3 points in the anterior, medial and posterior part, respectively. Both muscles were examined for the presence of active TrPs over each of the 9 points. The referred pain pattern of each active TrP was assessed. Two-way analysis of variance detected significant differences in mean PPT levels between the measurement points (F=30.3; P<0.001), but not between sides (F=2.1; P=0.2). PPT scores decreased from the posterior to the anterior column (P<0.001). No differences were found in the number of active TrPs (F=0.3; P=0.9) between the dominant side the nondominant side. Significant differences were found in the distribution of the active TrPs (chi2=12.2; P<0.001): active TrPs were mostly found in the anterior column and in the middle of the muscle belly. The analysis of variance did not detect significant differences in the referred pain pattern between active TrPs (F=1.1, P=0.4). The topographical pressure pain sensitivity maps showed the distinct distribution of the TrPs indicated by locations with low PPTs. Multiple active TrPs in the temporalis muscle were found, particularly in the anterior column and in the middle of the muscle belly. Bilateral posterior to anterior decreased distribution of PPTs in the temporalis muscle in women with CTTH was found. The locations of active TrPs in the temporalis muscle corresponded well to the muscle areas with lower PPT, supporting the relationship between multiple active muscle TrPs and topographical pressure sensitivity maps in the temporalis muscle in women with CTTH.

The distribution of Abbott high-sensitivity troponin I levels in Korean patients with chest pain.

PubMed

Lee, Kyunghoon; Lee, Soo-Youn; Choi, Jin-Oh; Jeon, Eun-Seok; Park, Hyung-Doo

2015-01-01

Troponin is considered a primary biomarker for coronary heart disease. We investigated the clinical utility of the Abbott high-sensitivity cardiac troponin I (hs-TnI) assay in patients with various cardiac problems. Precision was investigated by ten levels of pooled sera and three levels of control materials. We determined Abbott hs-TnI levels in a total of 3314 Korean patients with chest pain, including acute myocardial infarction (n=381), unstable angina (n=327), stable angina (n=1361), variant angina (n=189), non-coronary artery diseases (n=236), and nonspecific chest pain (n=820). The 99(th) percentile cutoff was established by the plasma from the cardio-healthy subgroup and validated by 118 healthy individuals. The total coefficient of variation in patient pooled sera and controls ranged from 3.93-6.35% and 4.81-9.73%, respectively. There was a significant difference in hs-TnI among various cardiac problems: subjects with non-cardiac chest pain (median 1.7 pg/mL, 25%/75% quartile 1.1/2.8 pg/mL), variant angina (2.4 pg/mL,1.4/5.6 pg/mL), stable angina (3.7 pg/mL, 2.1/8.9 pg/mL), unstable angina (10.7 pg/mL, 3.7/61.7 pg/mL), and non-coronary artery diseases (9.3 pg/mL, 4.3/37.4 pg/mL). However, the median levels of hs-TnI were not statistically different (p=0.921) between unstable angina and non-coronary artery diseases. The overall 99(th) percentile cutoff was 19.3 pg/mL (range 0.2-30.6 pg/mL). This new hs-TnI assay may be helpful in determining a differential diagnosis in patients with chest pain. © 2015 by the Association of Clinical Scientists, Inc.

Painful Shoulder in Swimmers: A Diagnostic Challenge.

ERIC Educational Resources Information Center

McMaster, William C.

1986-01-01

This article discusses the incidence, diagnosis, and treatment of painful shoulder in swimmers, including: regional problems that can cause shoulder pain; physical, clinical, and laboratory tests for diagnostic use; and approaches to management of the problem. (Author/CB)

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.

Plain abdominal radiography in acute abdominal pain; past, present, and future

PubMed Central

Gans, Sarah L; Stoker, Jaap; Boermeester, Marja A

2012-01-01

Several studies have demonstrated that a diagnosis based solely on a patient’s medical history, physical examination, and laboratory tests is not reliable enough, despite the fact that these aspects are essential parts of the workup of a patient presenting with acute abdominal pain. Traditionally, imaging workup starts with abdominal radiography. However, numerous studies have demonstrated low sensitivity and accuracy for plain abdominal radiography in the evaluation of acute abdominal pain as well as various specific diseases such as perforated viscus, bowel obstruction, ingested foreign body, and ureteral stones. Computed tomography, and in particular computed tomography after negative ultrasonography, provides a better workup than plain abdominal radiography alone. The benefits of computed tomography lie in decision-making for management, planning of a surgical strategy, and possibly even avoidance of negative laparotomies. Based on abundant available evidence, major advances in diagnostic imaging, and changes in the management of certain diseases, we can conclude that there is no place for plain abdominal radiography in the workup of adult patients with acute abdominal pain presenting in the emergency department in current practice. PMID:22807640

[Changes in pain sensitivity after the ablation of the somatosensory areas of the cerebral cortex in cats].

PubMed

Reshetniak, V K; Kukushkin, M L

1986-12-01

The effects of ablation of the first and second somatosensory cortex on pain sensitivity were studied in the behavioural experiments on adult cats. The ablation of the first somatosensory cortex (SI) was shown to cause an increase of the response thresholds at all the levels of a conventional scale, while the destruction of the second somatosensory cortex (S2) decreased the response thresholds. The role of SI and S2 in the evaluation of nociceptive information is discussed.

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.

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.

Visceral Pain: The Neurophysiological Mechanism

PubMed Central

Sengupta, Jyoti N.

2011-01-01

The mechanism of visceral pain is still less understood compared with that of somatic pain. This is primarily due to the diverse nature of visceral pain compounded by multiple factors such as sexual dimorphism, psychological stress, genetic trait, and the nature of predisposed disease. Due to multiple contributing factors there is an enormous challenge to develop animal models that ideally mimic the exact disease condition. In spite of that, it is well recognized that visceral hypersensitivity can occur due to (1) sensitization of primary sensory afferents innervating the viscera, (2) hyperexcitability of spinal ascending neurons (central sensitization) receiving synaptic input from the viscera, and (3) dysregulation of descending pathways that modulate spinal nociceptive transmission. Depending on the type of stimulus condition, different neural pathways are involved in chronic pain. In early-life psychological stress such as maternal separation, chronic pain occurs later in life due to dysregulation of the hypothalamic–pituitary–adrenal axis and significant increase in corticotrophin releasing factor (CRF) secretion. In contrast, in early-life inflammatory conditions such as colitis and cystitis, there is dysregulation of the descending opioidergic system that results excessive pain perception (i.e., visceral hyperalgesia). Functional bowel disorders and chronic pelvic pain represent unexplained pain that is not associated with identifiable organic diseases. Often pain overlaps between two organs and approximately 35% of patients with chronic pelvic pain showed significant improvement when treated for functional bowel disorders. Animal studies have documented that two main components such as (1) dichotomy of primary afferent fibers innervating two pelvic organs and (2) common convergence of two afferent fibers onto a spinal dorsal horn are contributing factors for organ-to-organ pain overlap. With reports emerging about the varieties of peptide molecules

Assessing the Exposure and Relative Sensitivity of Native Freshwater Mussels to Environmental Stressors and Laboratory Conditions

EPA Science Inventory

1. Expands the database for pesticide toxicity on native freshwater mussels. 2. Aids in determining any potential differences in toxic sensitivity of gravid female mussel attributed to age and laboratory holding times. 3. Aids in determining potential differences in juvenile ...

An inter-laboratory comparison of PNH clone detection by high-sensitivity flow cytometry in a Russian cohort.

PubMed

Sipol, Alexandra A; Babenko, Elena V; Borisov, Vyacheslav I; Naumova, Elena V; Boyakova, Elena V; Yakunin, Dimitry I; Glazanova, Tatyana V; Chubukina, Zhanna V; Pronkina, Natalya V; Popov, Alexander M; Saveliev, Leonid I; Lugovskaya, Svetlana A; Lisukov, Igor A; Kulagin, Alexander D; Illingworth, Andrea J

2015-01-01