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Sample records for laboratory pain sensitivity

  1. Sleep Disorders and their Association with Laboratory Pain Sensitivity in Temporomandibular Joint Disorder

    PubMed Central

    Smith, Michael T.; Wickwire, Emerson M.; Grace, Edward G.; Edwards, Robert R.; Buenaver, Luis F.; Peterson, Stephen; Klick, Brendan; Haythornthwaite, Jennifer A.

    2009-01-01

    Study Objectives: We characterized sleep disorder rates in temporomandibular joint disorder (TMD) and evaluated possible associations between sleep disorders and laboratory measures of pain sensitivity. Design: Research diagnostic examinations were conducted, followed by two consecutive overnight polysomnographic studies with morning and evening assessments of pain threshold. Setting: Orofacial pain clinic and inpatient sleep research facility Participants: Fifty-three patients meeting research diagnostic criteria for myofascial TMD. Interventions: N/A Measurements and Results: We determined sleep disorder diagnostic rates and conducted algometric measures of pressure pain threshold on the masseter and forearm. Heat pain threshold was measured on the forearm; 75% met self-report criteria for sleep bruxism, but only 17% met PSG criteria for active sleep bruxism. Two or more sleep disorders were diagnosed in 43% of patients. Insomnia disorder (36%) and sleep apnea (28.4%) demonstrated the highest frequencies. Primary insomnia (PI) (26%) comprised the largest subcategory of insomnia. Even after controlling for multiple potential confounds, PI was associated with reduced mechanical and thermal pain thresholds at all sites (P < 0.05). Conversely, the respiratory disturbance index was associated with increased mechanical pain thresholds on the forearm (P < 0.05). Conclusions: High rates of PI and sleep apnea highlight the need to refer TMD patients complaining of sleep disturbance for polysomnographic evaluation. The association of PI and hyperalgesia at a non-orofacial site suggests that PI may be linked with central sensitivity and could play an etiologic role in idiopathic pain disorders. The association between sleep disordered breathing and hypoalgesia requires further study and may provide novel insight into the complex interactions between sleep and pain-regulatory processes. Citation: Smith MT; Wickwire EM; Grace EG; Edwards RR; Buenaver LF; Peterson S; Klick B

  2. Relationship of neuroticism and laboratory pain in healthy children: does anxiety sensitivity play a role?

    PubMed

    Payne, Laura A; Seidman, Laura C; Lung, Kirsten C; Zeltzer, Lonnie K; Tsao, Jennie C I

    2013-01-01

    Both neuroticism, a higher-order, stable personality trait, and anxiety sensitivity (AS), a lower-order pain-related construct, have been associated with pain, although no research exists examining the relationship of both these constructs to acute pain in children. In the current study, 99 healthy children (53 girls) completed self-report measures of neuroticism and AS before undergoing pain tasks involving cold and pressure pain. We hypothesized that both neuroticism and AS would be correlated with acute pain responses, but that AS would at least partially mediate the relationship between neuroticism and pain responses. Results indicated significant correlations between neuroticism, AS, and anticipatory anxiety, pain intensity and pain bother. Mediational models revealed that AS partially mediated relationships between neuroticism and pain intensity/bother, and fully mediated relationships between neuroticism and anticipatory anxiety. These data suggest that, at least in children, neuroticism may be best understood as a vulnerability factor for elevated pain responses, especially when coupled with a fear of bodily sensations.

  3. Relationship of child perceptions of maternal pain to children's laboratory and non-laboratory pain.

    PubMed

    Evans, S; Tsao, J Ci; Zeltzer, L K

    2008-01-01

    Previous research has established links between parent and child pain. However, little is known about sex-specific parent-child pain relationships in a nonclinical population. A sample of 186 children aged eight to 18 years (49% female) provided information on maternal and self bodily pain, assessed by asking children about the presence and location of bodily pain experienced. Children also completed three laboratory pain tasks and reported on cold pressor pain intensity, pressure pain intensity and heat pain intensity. The presence of child-reported maternal pain was consistently correlated with daughters' bodily and laboratory pain, but not with sons' pain in bivariate analyses. Multivariate analyses controlling for child age and maternal psychological distress indicated that children of mothers with bodily pain reported more total bodily pain sites as well as greater pressure and cold pain intensity, relative to children of mothers without bodily pain. For cold pain intensity, these results differed for boys versus girls, in that daughters reporting maternal pain evidenced significantly higher cold pain intensity compared with daughters not reporting maternal pain. No such differences were found for boys. The findings suggest that children's perceptions of maternal pain may play a role in influencing children's own experience of pain, and that maternal pain models may affect boys and girls differently.

  4. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    PubMed Central

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  5. Exercise-induced pain intensity predicted by pre-exercise fear of pain and pain sensitivity

    PubMed Central

    Bishop, Mark D; Horn, Maggie E; George, Steven Z

    2011-01-01

    Objectives Our primary goals were to determine whether pre-existing fear of pain and pain sensitivity contributed to post-exercise pain intensity. Methods Delayed onset muscle pain was induced in the trunk extensors of 60 healthy volunteers using an exercise paradigm. Levels of fear of pain and experimental pain sensitivity were measured before exercise. Pain intensity in the low back was collected at 24 and 48 hours post-exercise. Participants were grouped based on pain intensity. Group membership was used as the dependent variable in separate regression models for 24 and 48 hours. Predictor variables included fear, pain sensitivity, torque lost during the exercise protocol, and demographic variables. Results The final models predicting whether a participant reported clinically meaningful pain intensity at 24 hours only included baseline fear of pain at each level of pain intensity tested. The final model at 48 hours included average baseline pain sensitivity and the loss of muscle performance during the exercise protocol for one level of pain intensity tested (greater than 35mm out of 100). Discussion Combined, these findings suggest that the initial reports of pain after injury maybe more strongly influenced by fear while the inflammatory process and pain sensitivity may play a larger role for later pain intensity reports. PMID:21415719

  6. 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.

  7. Dynamic, but not static, pain sensitivity predicts exercise-induced muscle pain: Covariation of temporal sensory summation and pain intensity

    PubMed Central

    Bishop, Mark D.; George, Steven Z.; Robinson, Michael E.

    2016-01-01

    Cross-section studies suggest that measures of pain sensitivity, derived from quantitative sensory testing (QST), are elevated in persons with chronic pain conditions. However, little is known about whether development of chronic pain is preceded by elevated pain sensitivity or pain sensitivity increases as a result of prolonged experience of pain. Here we used QST to test static (single suprathreshold stimuli) and dynamic (temporal sensory summation) pain processing of thermal stimuli. Muscle pain was induced using high-intensity exercise (DOMS). Multi-level modeling approaches determined the daily covariation among static and dynamic QST measures and pain intensity. Variation in responses to static pain sensitivity was not associated with pain intensity from DOMS while, in contrast, variation in dynamic pain sensitivity was positively associated with variation in pain intensity from DOMS. This finding supports the use of TSS as a marker of the central pain state and potentially as an appropriate measure for treatment monitoring. PMID:22967843

  8. Pain Sensitivity and Recovery From Mild Chronic Sleep Loss

    PubMed Central

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

    2012-01-01

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

  9. Cockroach sensitization in laboratory workers.

    PubMed

    Steinberg, D R; Bernstein, D I; Gallagher, J S; Arlian, L; Bernstein, I L

    1987-10-01

    Six laboratory workers who were exposed to American cockroaches (AC) and German cockroaches (GC) while they were performing immunologic experiments were evaluated for cockroach hypersensitivity. Prick skin testing and RAST were performed with whole body extracts (1:20 wt/vol) of AC, brown-banded (BB), and GC species as well as hemolymph and fecal (F) extracts of AC. Three of six workers reported work-related nasal and ocular symptoms associated with xenografting and bleeding of cockroaches. All three symptomatic workers exhibited cutaneous reactivity to at least one cockroach antigen. Elevated RAST binding was observed in one of the three symptomatic workers. A nasal provocation to AC was positive in the most symptomatic worker at a provocative dose of 3.2 X 10(-3) mg causing a 50% decrease of nasal flow rate from baseline. After pretreatment with nasal cromolyn, the provocative dose causing a 50% decrease from baseline increased to 2.6 X 10(-1) mg. Nasal provocation with the same concentrations of AC were negative in two skin test negative subjects. RAST-inhibition studies demonstrated cross inhibition of the serum-specific IgE binding to AC-hemolymph by AC, GC, and BB whole body extracts. However, specific IgE binding to AC-F was inhibited by AC-F and AC but not by GC or BB whole body extracts, suggesting there was greater specificity of the F allergens. This study demonstrated that cockroach allergens elicit IgE-dependent upper respiratory sensitization in the workplace.

  10. Pain sensitivity profiles in patients with advanced knee osteoarthritis.

    PubMed

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

    2016-09-01

    The development of patient profiles to subgroup individuals on a variety of variables has gained attention as a potential means to better inform clinical decision making. Patterns of pain sensitivity response specific to quantitative sensory testing (QST) modality have been demonstrated in healthy subjects. It has not been determined whether these patterns persist in a knee osteoarthritis population. In a sample of 218 participants, 19 QST measures along with pain, psychological factors, self-reported function, and quality of life were assessed before total knee arthroplasty. Component analysis was used to identify commonalities across the 19 QST assessments to produce standardized pain sensitivity factors. Cluster analysis then grouped individuals who exhibited similar patterns of standardized pain sensitivity component scores. The QST resulted in 4 pain sensitivity components: heat, punctate, temporal summation, and pressure. Cluster analysis resulted in 5 pain sensitivity profiles: a "low pressure pain" group, an "average pain" group, and 3 "high pain" sensitivity groups who were sensitive to different modalities (punctate, heat, and temporal summation). Pain and function differed between pain sensitivity profiles, along with sex distribution; however, no differences in osteoarthritis grade, medication use, or psychological traits were found. Residualizing QST data by age and sex resulted in similar components and pain sensitivity profiles. Furthermore, these profiles are surprisingly similar to those reported in healthy populations, which suggests that individual differences in pain sensitivity are a robust finding even in an older population with significant disease.

  11. Preoperative widespread pain sensitization and chronic pain after hip and knee replacement: a cohort analysis

    PubMed Central

    Wylde, Vikki; Sayers, Adrian; Lenguerrand, Erik; Gooberman-Hill, Rachael; Pyke, Mark; Beswick, Andrew D.; Dieppe, Paul; Blom, Ashley W.

    2015-01-01

    Abstract Chronic pain after joint replacement is common, affecting approximately 10% of patients after total hip replacement (THR) and 20% of patients after total knee replacement (TKR). Heightened generalized sensitivity to nociceptive input could be a risk factor for the development of this pain. The primary aim of this study was to investigate whether preoperative widespread pain sensitivity was associated with chronic pain after joint replacement. Data were analyzed from 254 patients receiving THR and 239 patients receiving TKR. Pain was assessed preoperatively and at 12 months after surgery using the Western Ontario and McMaster Universities Osteoarthritis Pain Scale. Preoperative widespread pain sensitivity was assessed through measurement of pressure pain thresholds (PPTs) at the forearm using an algometer. Statistical analysis was conducted using linear regression and linear mixed models, and adjustments were made for confounding variables. In both the THR and TKR cohort, lower PPTs (heightened widespread pain sensitivity) were significantly associated with higher preoperative pain severity. Lower PPTs were also significantly associated with higher pain severity at 12 months after surgery in the THR cohort. However, PPTs were not associated with the change in pain severity from preoperative to 12 months postoperative in either the TKR or THR cohort. These findings suggest that although preoperative widespread pressure pain sensitivity is associated with pain severity before and after joint replacement, it is not a predictor of the amount of pain relief that patients gain from joint replacement surgery, independent of preoperative pain severity. PMID:25599300

  12. Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition

    PubMed Central

    Bulls, Hailey W; Freeman, Emily L; Anderson, Austen JB; Robbins, Meredith T; Ness, Timothy J; Goodin, Burel R

    2015-01-01

    It has been suggested that increased pain sensitivity and disruption of endogenous pain inhibitory processes may account, at least in part, for the greater prevalence and severity of chronic pain in women compared to men. However, previous studies addressing this topic have produced mixed findings. This study examined sex differences in pain sensitivity and inhibition using quantitative sensory testing (QST), while also considering the influence of other important factors such as depressive symptoms and sleep quality. Healthy men (n=24) and women (n=24) each completed a QST battery. This battery included an ischemic pain task (IPT) that used a submaximal effort tourniquet procedure as well as a conditioned pain modulation (CPM) procedure for the assessment of endogenous pain inhibition. Prior to QST, participants completed the Center for Epidemiologic Studies Depression Scale and the Pittsburgh Sleep Quality Index. Analyses revealed significant sex differences for the ischemic pain task and the conditioned pain modulation procedure, such that women tolerated the ischemic pain for a shorter amount of time and demonstrated less pain inhibition compared with men. This remained true even when accounting for sex differences in depressive symptoms and sleep quality. The results of this study suggest that women may be more pain sensitive and possess less-efficient endogenous pain inhibitory capacity compared with men. Whether interventions that decrease pain sensitivity and enhance pain inhibition in women ultimately improve their clinical pain outcomes is an area of research that deserves additional attention in the future. PMID:26170713

  13. Demographic Predictors of Pain Sensitivity: Results From the OPPERA Study.

    PubMed

    Ostrom, Cara; Bair, Eric; Maixner, William; Dubner, Ronald; Fillingim, Roger B; Ohrbach, Richard; Slade, Gary D; Greenspan, Joel D

    2017-03-01

    The demographic factors of sex, age, and race/ethnicity are well recognized as relevant to pain sensitivity and clinical pain expression. Of these, sex differences have been the most frequently studied, and most of the literature describes greater pain sensitivity for women. The other 2 factors have been less frequently evaluated, and current literature is not definitive. Taking advantage of the large Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study cohort, we evaluated the association of sex, age, and self-reported race with 34 measures of pressure, mechanical, and thermal pain sensitivity encompassing threshold and suprathreshold perception. Women were significantly more pain-sensitive than men for 29 of 34 measures. Age effects were small, and only significant for 7 of 34 measures, however, the age range was limited (18-44 years of age). Race/ethnicity differences varied across groups and pain assessment type. Non-Hispanic white individuals were less pain-sensitive than African-American (for 21 of 34 measures), Hispanic (19 of 34), and Asian (6 of 34) individuals. No pain threshold measure showed significant racial differences, whereas several suprathreshold pain measures did. This suggests that racial differences are not related to tissue characteristics or inherent nociceptor sensitivity. Rather, the differences observed for suprathreshold pain ratings or tolerance are more likely related to differences in central nociceptive processing, including modulation imposed by cognitive, psychological, and/or affective factors.

  14. Amantadine sulfate reduces experimental sensitization and pain in chronic back pain patients.

    PubMed

    Kleinböhl, Dieter; Görtelmeyer, Roman; Bender, Hans-Joachim; Hölzl, Rupert

    2006-03-01

    We investigated if established psychophysical measures of enhanced experimental sensitization in chronic musculoskeletal pain can be reduced by adjuvant treatment with a N-methyl-d-aspartate receptor antagonist, amantadine sulfate, and whether a reduction in sensitization might be accompanied by a concurrent improvement in clinical pain. Sensitization was evaluated by an experimental tonic heat model of short-term sensitization with concurrent subjective and behavioral psychophysical scaling. Twenty-six patients with chronic back pain were included in the randomized, double-blind, placebo-controlled study and received daily dosages of either placebo or 100 mg of amantadine sulfate during a 1-wk treatment. Participants completed quantitative sensory testing of pain thresholds and experimental sensitization before and after treatment and clinical pain ratings before, during, and after treatment. Experimental sensitization and clinical pain were reduced in patients receiving verum. Initially, experimental sensitization was enhanced in patients, with early sensitization at nonpainful intensities of contact heat and enhanced sensitization at painful intensities, as shown previously. After 1 wk of treatment, experimental sensitization was reduced with amantadine sulfate but not with placebo. We conclude that adjuvant chronic pain treatment with N-methyl-d-aspartate receptor antagonists might be beneficial for chronic pain if enhanced sensitization is involved and that the quantitative sensory test of temporal summation may be used to verify this.

  15. Characteristics of sensitization associated with chronic pain conditions

    PubMed Central

    Vierck, Charles J.; Wong, Fong; King, Christopher D.; Mauderli, Andre P.; Schmidt, Siegfried; Riley, Joseph L.

    2014-01-01

    Objectives To describe and understand varieties and characteristics of sensitization contributing to hyperalgesia for patients with chronic pain conditions. Methods Thermal stimulation was delivered to the face, forearm and calf of pain-free subjects and individuals with irritable bowel syndrome (IBS), temporomandibular pain disorder (TMD) and fibromyalgia syndrome (FMS). Three second contacts of a preheated thermode occurred at 30 sec. intervals in ascending and then descending series (0.7°C steps). Results Thermal pain ratings during ascending series were greater at each site for individuals diagnosed with chronic pain. Strong pain at the time of testing further enhanced the ratings at all sites, but mild or moderate clinical pain did not have this effect. Thermal pain for all subjects was greater during descending series than during ascending series of arm and leg stimulation. The hypersensitivity during descending series was comparable for pain-free, FMS and TMD subjects but was increased in duration for arm or leg stimulation of FMS subjects. Discussion The widespread sensitization for IBS and TMD subjects does not rely on mechanisms of spatial and temporal summation often invoked to explain widespread hyperalgesia associated with chronic pain. Increased sensitivity during descending series during stimulation of an arm or leg but not the face indicates a propensity for sensitization of nociceptive input to the spinal cord. Abnormally prolonged sensitization for FMS patients reveals a unique influence of widespread chronic pain referred to deep somatic tissues. PMID:23629594

  16. Central sensitization: implications for the diagnosis and treatment of pain.

    PubMed

    Woolf, Clifford J

    2011-03-01

    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 post-surgical 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 in both 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

  17. 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

  18. 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.

  19. Cerebral Cortical Thickness in Chronic Pain Due to Knee Osteoarthritis: The Effect of Pain Duration and Pain Sensitization

    PubMed Central

    2016-01-01

    Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role. PMID:27658292

  20. Mucosal versus muscle pain sensitivity in provoked vestibulodynia

    PubMed Central

    Witzeman, Kathryn; Nguyen, Ruby HN; Eanes, Alisa; As-Sanie, Sawsan; Zolnoun, Denniz

    2015-01-01

    Background An estimated 8.3%—16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD). Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy. Objective To explore the relative contribution of mucosal versus muscle pain sensitivity on pain report from intercourse among women with PVD. Design In this proof of concept study, 54 women with PVD underwent a structured examination assessing mucosal and pelvic muscle sensitivity. Methods We examined three mucosal sites in the upper and lower vestibule. Patients were asked to rate their pain on cotton swab palpation of the mucosa using a 10-point visual analog scale. Muscle pain was assessed using transvaginal application of pressure on right and left puborectalis, and the perineal muscle complex. The Gracely pain scale (0–100) was used to assess the severity of pain with intercourse, with women rating the lowest, average, and highest pain levels; a 100 rating the highest level of pain. Results The lower vestibule’s mucosa 5.81 (standard deviation =2.83) was significantly more sensitive than the upper vestibule 2.52 (standard deviation =2.6) (P<0.01) on exam. However, mucosal sensitivity was not associated with intercourse pain, while muscle sensitivity was moderately associated with both average and highest intensity of intercourse pain (r=−0.46, P=0.01 and r=−0.42, P=0.02), respectively. Conclusion This preliminary study suggests that mucosal measures alone may not sufficiently capture the spectrum of clinical pain report in women with PVD, which is consistent with the empirical success of physical therapy in this population. PMID:26316805

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

    PubMed Central

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

    2014-01-01

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

  2. 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

  3. Relating Chronic Pelvic Pain and Endometriosis to Signs of Sensitization and Myofascial Pain and Dysfunction.

    PubMed

    Aredo, Jacqueline V; Heyrana, Katrina J; Karp, Barbara I; Shah, Jay P; Stratton, Pamela

    2017-01-01

    Chronic pelvic pain is a frustrating symptom for patients with endometriosis and is frequently refractory to hormonal and surgical management. While these therapies target ectopic endometrial lesions, they do not directly address pain due to central sensitization of the nervous system and myofascial dysfunction, which can continue to generate pain from myofascial trigger points even after traditional treatments are optimized. This article provides a background for understanding how endometriosis facilitates remodeling of neural networks, contributing to sensitization and generation of myofascial trigger points. A framework for evaluating such sensitization and myofascial trigger points in a clinical setting is presented. Treatments that specifically address myofascial pain secondary to spontaneously painful myofascial trigger points and their putative mechanisms of action are also reviewed, including physical therapy, dry needling, anesthetic injections, and botulinum toxin injections.

  4. Pain treatment for patients with osteoarthritis and central sensitization.

    PubMed

    Lluch Girbés, Enrique; Nijs, Jo; Torres-Cueco, Rafael; López Cubas, Carlos

    2013-06-01

    Osteoarthritis is one of the most frequent, disabling, and costly pathologies of modern society. Among the main aims of osteoarthritis management are pain control and functional ability improvement. The exact cause of osteoarthritis pain remains unclear. In addition to the pathological changes in articular structures, changes in central pain processing or central sensitization appear to be involved in osteoarthritis pain. The latter calls for a broader approach to the management of patients with osteoarthritis. Yet, the scientific literature offers scant information addressing the treatment of central sensitization, specifically in patients with osteoarthritis. Interventions such as cognitive-behavioral therapy and neuroscience education potentially target cognitive-emotional sensitization (and descending facilitation), and centrally acting drugs and exercise therapy can improve endogenous analgesia (descending inhibition) in patients with osteoarthritis. Future studies should assess these new treatment avenues.

  5. Pain complaint and the weather: weather sensitivity and symptom complaints in chronic pain patients.

    PubMed

    Shutty, M S; Cundiff, G; DeGood, D E

    1992-05-01

    Chronic pain patients frequently report that weather conditions affect their pain; however, no standardized measures of weather sensitivity have been developed. We describe the development and use of the Weather and Pain Questionnaire (WPQ) which assess patient sensitivity to meteorologic variables defined by the National Weather Service (e.g., temperature, precipitation). Seventy chronic pain patients (59% females) with an average age of 43 years completed the WPQ. The instrument was revised using factor analysis to produce a Weather Sensitivity Index (WSI) (48% of variance) with high internal consistency (0.93) and test-retest reliability (r = 0.89). Reporting patterns suggested that patients could reliably identify which meteorologic variables influenced their pain but could not reliably determine which physical symptoms were consistently affected. The most frequently reported meteorologic variables which affect pain complaint were temperature (87%) and humidity (77%). The most frequently reported physical complaints associated with the weather were joint and muscle aches (82% and 79%, respectively). Patients labeled as being 'weather sensitive', defined by greater than median scores on the WPQ, reported significantly greater pain intensity, greater chronicity of pain problems, and more difficulties sleeping than patients with low scores on the WPQ. No differences in gender, education level, disability status, or global psychological distress were found. Results are discussed with respect to physiological and psychological mediating variables.

  6. 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

  7. Pain Sensitivity and Opioid Analgesia: A Pharmacogenomic Twin Study

    PubMed Central

    Angst, Martin S.; Phillips, Nicholas G.; Drover, David R.; Tingle, Martha; Ray, Amrita; Swan, Gary E.; Lazzeroni, Laura C.; Clark, J. David

    2012-01-01

    Opioids are the cornerstone medication for the management of moderate to severe pain. Unfortunately, vast inter-individual differences in dose requirements complicate their effective and safe clinical use. Mechanisms underlying such differences are incompletely understood, are likely multifactorial, and include genetic and environmental contributions. While accumulating evidence suggests that variants of several genes account for some of the observed response variance, the relative contribution of these factors remains unknown. This study used a twin paradigm to provide a global estimate of the genetic and environmental contributions to inter-individual differences in pain sensitivity and analgesic opioid effects. Eighty one monozygotic and 31 dizygotic twin pairs successfully underwent a computer-controlled infusion with the muopioid agonist alfentanil in a single occasion, randomized, double-blind and placebo-controlled study design. Pain sensitivity and analgesic effects were assessed with experimental heat and cold pressor pain models along with important covariates including demographic factors, depression, anxiety, and sleep quality. Significant heritability was detected for cold pressor pain tolerance and opioid-mediated elevations in heat and cold pressor pain thresholds. Genetic effects accounted for 12–60% of the observed response variance. Significant familial effects accounting for 24–32% of observed variance were detected for heat and cold pressor pain thresholds and opioid-mediated elevation in cold pressor pain tolerance. Significant covariates included age, gender, race, education, and anxiety. Results provide a strong rationale for more detailed molecular genetic studies to elucidate mechanisms underlying inter-individual differences in pain sensitivity and analgesic opioid responses. Such studies will require careful consideration of the studied pain phenotype. PMID:22444188

  8. 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

  9. 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

  10. 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

  11. Decreased pain sensitivity among people with schizophrenia: a meta-analysis of experimental pain induction studies.

    PubMed

    Stubbs, Brendon; Thompson, Trevor; Acaster, Sarah; Vancampfort, Davy; Gaughran, Fiona; Correll, Christoph U

    2015-11-01

    Patients with schizophrenia report reduced pain sensitivity in clinical studies, but experimental studies are required to establish pain sensitivity as a potential endophenotype. We conducted a systematic review of electronic databases from database inception until April 15, 2015, including experimental studies investigating pain among patients with schizophrenia spectrum disorder vs healthy controls. A random-effect meta-analysis yielding Hedges' g ±95% confidence intervals (CIs) as the effect size (ES) measure was conducted. Primary outcome was a pooled composite of pain threshold and pain tolerance; secondary outcomes included these parameters individually, plus sensory threshold, physiological pain response, and pain intensity or unpleasantness. Across 17 studies, patients with schizophrenia spectrum disorder (n = 387; age, 30.7 ± 6.9 years; females, 31.9%; illness duration, 7.0 ± 5.7 years) were compared with controls (n = 483; age, 29.5 ± 7.4 years; females, 31.0%). Patients had elevated pain threshold/pain tolerance vs controls (ES = 0.583; 95% CI, 0.212-0.954; P = 0.002; studies = 15). Results were similar in antipsychotic-free individuals (ES = 0.599; 95% CI, 0.291-0.907; P < 0.0001; studies = 8), with trend-level significance in antipsychotic-treated individuals (ES = 0.566; 95% CI, -0.007 to 1.125; P = 0.047; studies = 9). Likewise, patients with schizophrenia had increased pain tolerance (ES = 0.566; 95% CI, 0.235-0.897; P = 0.0001; studies = 6), sensory threshold (ES = 1.16; 95% CI, 0.505-1.727; P < 0.0001; studies = 5), and pain threshold (ES = 0.696; 95% CI, 0.407-0.986; P < 0.001; studies = 9), as well as reduced physiological response to noxious stimuli (ES = 0.456; 95% CI, 0.131-0.783; P = 0.006) and pain intensity/unpleasantness ratings (ES = 0.547; 95% CI, 0.146-0.949; P = 0.008). Findings were similarly significant in antipsychotic-free patients with schizophrenia (analysable parameters = 4) and antipsychotic-treated individuals (analysable

  12. Development of the Geop-Pain questionnaire for multidisciplinary assessment of pain sensitivity

    PubMed Central

    Ko, Su-Hwan; Lee, Mi-Soon; Koo, Bon-Sung; Lee, Joon-Ho; Kim, Sang-Hyun; Chae, Won Seok; Jin, Hee Cheol; Lee, Jeong Seok; Kim, Yong-Ik

    2016-01-01

    Background To assess the multidisciplinary aspects of pain, various self-rating questionnaires have been developed, but there have not been sufficient relevant studies on this topic in South Korea. The aim of this study was to develop a new pain sensitivity-related questionnaire in the Korean language that would be simple and would well reflect Koreans' senses. Methods A new pain assessment questionnaire was developed through a pre-survey on "geop", which is the Korean word expressing fear, anxiety, or catastrophizing. We named the new assessment questionnaire the Geop-Pain Questionnaire (GPQ). The GPQ was composed of 15 items divided into three categories and rated on a 5-point scale. As a preliminary study, internal consistency and test-retest reliability analyses were conducted. Subsequently, 109 individuals completed the GPQ along with three pain-related questionnaires translated into Korean (Pain Sensitivity Questionnaire [PSQ], Pain Anxiety Symptoms Scale [PASS], and Pain Catastrophizing Scale [PCS]), and the correlations were analyzed. Results All items in the GPQ showed appropriate internal consistency, and the test-retest reliability analysis showed no statistically significant differences. The correlations between the GPQ and the existing questionnaires revealed that the GPQ scores had mid-positive correlations with the PSQ scores and strong positive correlations with the PASS and PCS scores. Conclusions This study attempted to develop a questionnaire assessing pain sensitivity multidimensionally using the Korean word geop for the first time. The self-rating GPQ showed high correlations with the existing questionnaires and demonstrated potential to be utilized as a pain prediction index in clinical practice. PMID:27703631

  13. Neural mechanisms underlying pain's ability to reorient attention: evidence for sensitization of somatic threat detectors.

    PubMed

    Dowman, Robert

    2014-06-01

    Pain typically signals damage to the body, and as such can be perceived as threatening and can elicit a strong emotional response. This ecological significance undoubtedly underlies pain's well-known ability to demand attention. However, the neural mechanisms underlying this ability are poorly understood. Previous work from the author's laboratory has reported behavioral evidence suggesting that participants disengage their attention from an incorrectly cued visual target stimulus and reorient it toward a somatic target more rapidly when the somatic target is painful than when it is nonpainful. Furthermore, electrophysiological data suggest that this effect is mediated by a stimulus-driven process, in which somatic threat detectors located in the dorsal posterior insula activate the medial and lateral prefrontal cortex areas involved in reorienting attention toward the painful target. In these previous studies, the painful and nonpainful somatic targets were given in separate experiments involving different participants. Here, the nonpainful and painful somatic targets were presented in random order within the same block of trials. Unlike in the previous studies, both the nonpainful and painful somatic targets activated the somatic threat detectors, and the times taken to disengage and reorient attention were the same for both. These electrophysiological and behavioral data suggest that somatic threat detectors can become sensitized to nonpainful somatic stimuli that are presented in a context that includes painful stimuli.

  14. Understanding Ocular Discomfort and Dryness Using the Pain Sensitivity Questionnaire

    PubMed Central

    Li, Wing; Graham, Andrew D.

    2016-01-01

    Purpose To utilize the Pain Sensitivity Questionnaire (PSQ) to assess the influence of pain sensitivity on perceptions of ocular discomfort and dryness. Methods Subjects completed a battery of questionnaires, including history of ocular and general health, contact lens wear history, the Ocular Surface Disease Index (OSDI) questionnaire, visual analog scale (VAS) 100-point rating scales to assess severity and frequency of average and end of day (EOD) discomfort and dryness, and the PSQ to assess pain sensitivity level. Masked subjects were then instructed to wear one inverted and one normally oriented soft contact lens contralaterally for 30 minutes to induce an inter-eye difference in comfort and dryness sensations. Subjects rated comfort and dryness in each eye on VAS every 5 minutes during contact lens wear. A slit lamp examination was performed to evaluate ocular surface health and to assess contact lens fit. Results One hundred and fifty-three subjects (111 females, 42 males) completed the study. In separate models, a higher PSQ score was significantly associated with higher OSDI score (p = 0.002), lower average and EOD comfort (p = 0.005 and 0.001, respectively), and greater EOD dryness (p = 0.04). The minimum (0.14) and maximum (7.14) PSQ scores observed in our subject cohort (i.e., from the subjects who were the least and most sensitive to pain, respectively) corresponded to an estimated difference of 11 points on the OSDI, 20 points on the VAS scale for average comfort, 31 points for EOD comfort and 17 points for EOD dryness. In a mixed effects model, a higher PSQ score was significantly associated with a greater inter-eye difference in comfort (p = 0.013) and dryness (p = 0.010) during CL wear. Conclusions Pain sensitivity influences perceptions of ocular discomfort and dryness, and should be taken into account when evaluating subjective assessments of these symptoms. PMID:27137908

  15. 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

  16. Oxidation-sensitive nociception involved in endometriosis-associated pain.

    PubMed

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

    2015-03-01

    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 and is rich in inflammatory markers, pain-inducing prostaglandins prostaglandin E2 and prostaglandin F2α, and lipid peroxides; and the endometriotic tissue is innervated with nociceptors. Our clinical study showed that 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 (1) the detection of lipoprotein-derived oxidation-sensitive pain molecules, (2) the ability of such molecules to induce nociception, and (3) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins to be similar to that seen in the PF. Oxidatively modified lipoproteins induced hypothermia (intracerebroventricular) 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 nonsteroidal anti-inflammatory drug 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 upregulation of similar genes belonging to opioid and inflammatory pathways. Our finding that oxidatively modified lipoproteins can induce nociception has a broader impact not only on the treatment of endometriosis-associated pain but also on other diseases associated with chronic pain.

  17. Healthy Volunteers Can Be Phenotyped Using Cutaneous Sensitization Pain Models

    PubMed Central

    Rowbotham, Michael C.; Dahl, Jørgen B.

    2013-01-01

    Background Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. Methods We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]). Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C), the brief thermal sensitization (BTS), and the burn injury (BI) models. Three studies included both the H/C and BTS models. Results Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC) improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into ‘small area’ (1st quartile [<25%]) and ‘large area’ (4th quartile [>75%]) responders: 56–76% of subjects consistently fell into same ‘small-area’ or ‘large-area’ category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm) and BTS (thigh) models. Conclusion Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models. PMID:23671631

  18. Pain extent is associated with pain intensity but not with widespread pressure or thermal pain sensitivity in women with fibromyalgia syndrome.

    PubMed

    Barbero, Marco; Fernández-de-Las-Peñas, César; Palacios-Ceña, María; Cescon, Corrado; Falla, Deborah

    2017-02-04

    Widespread pain is considered a sign of central sensitization in people with chronic pain. Our aim was to examine whether pain extent, assessed from the pain drawing, relates to measures from quantitative sensory testing in fibromyalgia syndrome (FMS). Thirty women with FMS and no other co-morbid conditions completed pain drawings (dorsal and ventral views) and clinical and related disability questionnaires. Pain extent and pain frequency maps were obtained from the pain drawings using a novel customized software. Pressure pain thresholds were assessed over the 18 tender points considered by the 1990 American College of Rheumatology criteria for FMS diagnosis and over two additional standardized points. Heat and cold pain thresholds were also assessed on the dorsal aspect of the neck, the dorsal aspect of the wrist, and the tibialis anterior. Spearman's correlation coefficients were used to assess the relationship between pain extent and quantitative sensory testing outcomes as well as clinical symptoms. Larger extent of pain was associated with a higher pain intensity (dorsal area: r s = 0.461, P = 0.010; total area: r s = 0.593, P = 0.001), younger age (ventral area: r s = -0.544, P = 0.002; total area: r s = -0.409, P = 0.025), shorter history of pain (ventral area: r s = -0.367, P = 0.046), and higher cold pain thresholds over the tibialis anterior muscle (r s = -0.406, P = 0.001). No significant association was observed between pain extent and the remaining outcomes. Pain drawings constitute an easy and accurate approach to quantify widespread pain. Larger pain extent is associated with pain intensity but not with signs of central sensitization in women with FMS.

  19. Maternal Anxiety and Children’s Laboratory Pain: The Mediating Role of Solicitousness

    PubMed Central

    Evans, Subhadra; Payne, Laura A.; Seidman, Laura; Lung, Kirsten; Zeltzer, Lonnie; Tsao, Jennie C. I.

    2016-01-01

    There has been limited empirical examination of how parent variables such as anxiety and solicitousness collectively impact child pain response. We sought to examine the relationships among maternal anxiety, solicitous parenting, and children’s laboratory anxiety and pain intensity in children with chronic pain. Participants included 80 children and adolescents (ages 8–18) with chronic pain and their mothers. Children completed questionnaires and lab pain tasks measuring their parents’ solicitous parenting, pressure, cold and heat pain anticipatory anxiety and pain intensity. Using bootstrapping analysis, maternal anxiety predicted child anticipatory anxiety and pain intensity in girls with chronic pain, which was mediated by the child’s report of parental solicitousness. For boys with chronic pain, maternal anxiety predicted boys’ anticipatory anxiety and pain intensity, with no support for mediation. This study adds to the growing literature demonstrating the impact of maternal anxiety on children’s pain. The study highlights the importance of considering parents in treatment designed to reduce children’s pain. PMID:27417248

  20. The mu opioid receptor A118G gene polymorphism moderates effects of trait anger-out on acute pain sensitivity.

    PubMed

    Bruehl, Stephen; Chung, Ok Y; Burns, John W

    2008-10-15

    Both trait anger-in (managing anger through suppression) and anger-out (managing anger through direct expression) are related to pain responsiveness, but only anger-out effects involve opioid mechanisms. Preliminary work suggested that the effects of anger-out on postoperative analgesic requirements were moderated by the A118G single nucleotide polymorphism of the mu opioid receptor gene. This study further explored these potential genotypexphenotype interactions as they impact acute pain sensitivity. Genetic samples and measures of anger-in and anger-out were obtained in 87 subjects (from three studies) who participated in controlled laboratory acute pain tasks (ischemic, finger pressure, thermal). McGill Pain Questionnaire (MPQ) Sensory and Affective ratings for each pain task were standardized within studies, aggregated across pain tasks, and combined for analyses. Significant anger-outxA118G interactions were observed (p's<.05). Simple effects tests for both pain measures revealed that whereas anger-out was nonsignificantly hyperalgesic in subjects homozygous for the wild-type allele, anger-out was significantly hypoalgesic in those with the variant G allele (p's<.05). For the MPQ-Affective measure, this interaction arose both from low pain sensitivity in high anger-out subjects with the G allele and heightened pain sensitivity in low anger-out subjects with the G allele relative to responses in homozygous wild-type subjects. No genetic moderation was observed for anger-in, although significant main effects on MPQ-Affective ratings were noted (p<.005). Anger-in main effects were due to overlap with negative affect, but anger-outxA118G interactions were not, suggesting unique effects of expressive anger regulation. Results support opioid-related genotypexphenotype interactions involving trait anger-out.

  1. 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.

  2. The effects of emotion regulation strategies on the pain experience: a structured laboratory investigation.

    PubMed

    Hampton, Amy J D; Hadjistavropoulos, Thomas; Gagnon, Michelle M; Williams, Jaime; Clark, David

    2015-05-01

    Although emotion regulation modulates the pain experience, inconsistencies have been identified regarding the impact of specific regulation strategies on pain. Our goal was to examine the effects of emotion suppression and cognitive reappraisal on automatic (ie, nonverbal) and cognitively mediated (ie, verbal) pain expressions. Nonclinical participants were randomized into either a suppression (n = 58), reappraisal (n = 51), or monitoring control (n = 42) condition. Upon arrival to the laboratory, participants completed the Emotion Regulation Questionnaire, to quantify self-reported suppression and reappraisal tendencies. Subsequently, they completed a thermal pain threshold and tolerance task. They were then provided with instructions to use, depending on their experimental condition, suppression, reappraisal, or monitoring strategies. Afterward, they were exposed to experimentally induced pain. Self-report measures of pain, anxiety, and tension were administered, and facial expressions, heart rate, and galvanic skin response were recorded. The Facial Action Coding System was used to quantify general and pain-related facial activity (ie, we defined facial actions that occurred during at least 5% of pain stimulation periods as "pain-related actions"). Reappraisal and suppression induction led to reductions in nonverbal and verbal indices of pain. Moreover, self-reported tendencies to use suppression and reappraisal (as measured by the Emotion Regulation Questionnaire) did not interact with experimental condition in the determination of participants' responses. Results suggest that consciously applying emotion regulation strategies during a painful task can moderate both cognitively mediated (e.g., verbal) and automatic (e.g., facial activity) expressions of pain.

  3. High Frequency Migraine Is Associated with Lower Acute Pain Sensitivity and Abnormal Insula Activity Related to Migraine Pain Intensity, Attack Frequency, and Pain Catastrophizing

    PubMed Central

    Mathur, Vani A.; Moayedi, Massieh; Keaser, Michael L.; Khan, Shariq A.; Hubbard, Catherine S.; Goyal, Madhav; Seminowicz, David A.

    2016-01-01

    Migraine is a pain disorder associated with abnormal brain structure and function, yet the effect of migraine on acute pain processing remains unclear. It also remains unclear whether altered pain-related brain responses and related structural changes are associated with clinical migraine characteristics. Using fMRI and three levels of thermal stimuli (non-painful, mildly painful, and moderately painful), we compared whole-brain activity between 14 migraine patients and 14 matched controls. Although, there were no significant differences in pain thresholds nor in pre-scan pain ratings to mildly painful thermal stimuli, patients did have aberrant suprathreshold nociceptive processing. Brain imaging showed that, compared to controls, patients had reduced activity in pain modulatory regions including left dorsolateral prefrontal, posterior parietal, and middle temporal cortices and, at a lower-threshold, greater activation in the right mid-insula to moderate pain vs. mild pain. We also found that pain-related activity in the insula was associated with clinical variables in patients, including associations between: bilateral anterior insula and pain catastrophizing (PCS); bilateral anterior insula and contralateral posterior insula and migraine pain intensity; and bilateral posterior insula and migraine frequency at a lower-threshold. PCS and migraine pain intensity were also negatively associated with activity in midline regions including posterior cingulate and medial prefrontal cortices. Diffusion tensor imaging revealed a negative correlation between fractional anisotropy (a measure of white matter integrity; FA) and migraine duration in the right mid-insula and a positive correlation between left mid-insula FA and PCS. In sum, while patients showed lower sensitivity to acute noxious stimuli, the neuroimaging findings suggest enhanced nociceptive processing and significantly disrupted modulatory networks, particularly involving the insula, associated with indices

  4. 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.

  5. Analysis of thermal pain sensitivity and psychological profiles in different subgroups of TMD patients.

    PubMed

    Park, J W; Clark, G T; Kim, Y K; Chung, J W

    2010-10-01

    This study evaluated differences in pain sensitivities and psychological profiles among different temporomandibular disorder (TMD) pain subtypes. Evaluation was done on 36 normal subjects and 39 TMD patients with high Graded Chronic Pain scale scores. TMD patients were placed in three pain subgroups (myogenous, arthrogenous, mixed) using the Research Diagnostic Criteria for TMD (RDC/TMD) axis I guidelines. RDC/TMD axis II profiles including depression and somatization were analysed. Cold pain threshold (CPT), heat pain threshold (HPT), and heat pain tolerance threshold (HPTT) were measured on three facial regions (anterior temporalis, masseter, TMJ) and a leg region (anterior tibialis). The arthrogenous pain subgroup showed significantly higher CPT and lower HPT and HPTT in the facial region, and lower HPTT in the anterior tibialis region compared with normal and myogenous pain subgroups. The myogenous pain subgroup had significantly higher somatization scores than normal and arthrogenous pain subgroups, and higher depression scores than normal subjects. The results suggest that peripheral and/or central sensitization are present in chronic arthrogenous pain more so than in myogenous pain, and this phenomenon appears to take place regardless of the patient's psychological profiles. These results may explain the underlying mechanism that aggravates TMD pain.

  6. Chronic Widespread Pain Drawn on a Body Diagram is a Screening Tool for Increased Pain Sensitization, Psycho-Social Load, and Utilization of Pain Management Strategies.

    PubMed

    Visser, Eric J; Ramachenderan, Jonathan; Davies, Stephanie J; Parsons, Richard

    2016-01-01

    The aim of this study was to investigate the hypothesis that chronic widespread pain, (CWP) drawn by patients on a body diagram, could be used as a screening tool for increased pain sensitization, psycho-social load, and utilization of pain management strategies. The triage questionnaires of 144 adults attending a chronic pain outpatients' clinic were audited and the percentage pain surface area (PPSA) drawn on their body diagrams was calculated using the "rule of nines" (RON) method for burns area assessment. Outcomes were measured using the painDETECT Questionnaire (PD-Q) and other indices and compared using a nonrandomized, case-control method. It was found that significantly more subjects with CWP (defined as a PPSA ≥ 20%) reported high (≥ 19) PD-Q scores (suggesting pain "sensitization" or neuropathic pain) (P = 0.0002), "severe" or "extremely severe" anxiety scores on the Depression, Anxiety and Stress Scale-21 Items Questionnaire (P = 0.0270), ≥ 5 psycho-social stressors (P = 0.0022), ≥ 5 significant life events (P = 0.0098), and used ≥ 7 pain management strategies (PMS) (P < 00001), compared to control subjects with a lower PPSA. A Widespread Pain Index score ≥ 7 (OR = 11.36), PD-Q score ≥ 19 (OR = 4.46) and use of ≥ 7 PMS (OR = 5.49) were independently associated with CWP. This study demonstrates that calculating PPSA on a body diagram (using the RON method) is a valid and convenient "snapshot" screening tool to identify patients with an increased likelihood of pain sensitization, psycho-social load, and utilizing pain management resources.

  7. Asians differ from non-Hispanic Whites in experimental pain sensitivity.

    PubMed

    Rowell, Lauren N; Mechlin, Beth; Ji, Ellen; Addamo, Michael; Girdler, Susan S

    2011-08-01

    This study examined differences between Asians and non-Hispanic Whites (Whites) in pain sensitivity, and its relationship to mean arterial pressure (MAP) and heart rate (HR). In 30 Whites (50% female) and 30 Asians (50% female), experimental pain sensitivity was assessed with a hand cold pressor task, yielding measures of pain threshold, tolerance, intensity, and unpleasantness. Mean arterial pressure and HR measurements taken at rest and in response to speech stress were assessed. Perceived stress, anxiety, perfectionism, parental criticism, parental expectations and depressive symptoms were also measured. The results indicated that for the cold pain test, Asians demonstrated significantly lower pain threshold and tolerance levels than Whites. Although no ethnic differences were seen for MAP or HR responses to stress, for Whites higher stress MAP levels were correlated with reduced pain sensitivity, while for Asians higher baseline and stress HR levels were correlated with reduced pain sensitivity. Asians reported higher parental expectations and greater parental criticism than Whites. For Asians only, higher levels of perfectionism were related to more depressive symptoms, anxiety and perceived stress. These results indicate that Asian Americans are more sensitive to experimental pain than Whites and suggest ethnic differences in endogenous pain regulatory mechanisms (e.g. MAP and HR). The results may also have implications for understanding ethnic differences in clinical pain.

  8. Pain Sensitivity and Observer Perception of Pain in Individuals with Autistic Spectrum Disorder

    PubMed Central

    Allely, C. S.

    2013-01-01

    The peer-reviewed literature investigating the relationship between pain expression and perception of pain in individuals with ASD is sparse. The aim of the present systematic PRIMSA review was twofold: first, to see what evidence there is for the widely held belief that individuals with ASD are insensitive to pain or have a high pain threshold in the peer-reviewed literature and, second, to examine whether individuals with ASD react or express pain differently. Fifteen studies investigating pain in individuals with ASD were identified. The case studies all reported pain insensitivity in individuals with ASD. However, the majority of the ten experimental studies reviewed indicate that the idea that individuals with ASD are pain insensitive needs to be challenged. The findings also highlight the strong possibility that not all children with ASD express their physical discomfort in the same way as a neurotypical child would (i.e., cry, moan, seek comfort, etc.) which may lead caregivers and the medical profession to interpret this as pain insensitivity or incorrectly lead them to believe that the child is in no pain. These results have important implications for the assessment and management of pain in children with ASD. PMID:23843740

  9. Anxiety sensitivity and catastrophizing: Associations with pain and somatization in non-clinical children

    PubMed Central

    Tsao, Jennie C. I.; Allen, Laura B.; Evans, Subhadra; Lu, Qian; Myers, Cynthia D.; Zeltzer, Lonnie K.

    2009-01-01

    This study examined the relationships among anxiety sensitivity (AS), catastrophizing, somatization, and pain in 240 non-clinical children (121 girls; mean age = 12.7 years). Children with pain problems (n = 81; 33.8%) reported greater AS and catastrophizing (p’s < .01) relative to children without pain problems. AS but not catastrophizing was significantly associated with current pain. However, both AS and catastrophizing were significantly associated with somatization. AS and catastrophizing represent related but partially distinct cognitive constructs that may be targeted by interventions aimed at alleviating pain and somatization in children. PMID:19858329

  10. Gender, variation in opioid receptor genes and sensitivity to experimental pain

    PubMed Central

    2013-01-01

    Background Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included. Results Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain. Conclusion This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions. PMID:23570317

  11. 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.

  12. Sad mood increases pain sensitivity upon thermal grill illusion stimulation: implications for central pain processing.

    PubMed

    Boettger, Michael Karl; Schwier, Christiane; Bär, Karl-Jürgen

    2011-01-01

    In different fields of neuroscience research, illusions have successfully been used to unravel underlying mechanisms of stimulus processing. One such illusion existing for the field of pain research is the so-called thermal grill illusion. Here, painful sensations are elicited by interlacing warm and cold bars, with stimulus intensities (temperatures) of these bars being below the respective heat pain or cold pain thresholds. To date, the underlying mechanisms of this phenomenon are not completely understood. There is some agreement, however, that the sensation evoked by this stimulation is generated by central nervous interactions. Therefore, we followed two approaches in this study: firstly, we aimed at developing and validating a water-driven device which might be used in fMRI scanners in future studies - subject to minor adaptations. Secondly, we aimed to interfere with this illusion by induction of a sad mood state, a procedure which is suggested to influence central nervous structures that are also involved in pain processing. The newly developed device induced thermal grill sensations similar to those reported in the literature. Induction of sad, but not neutral mood states, resulted in higher pain and unpleasantness ratings of the painful illusion. These findings might be of importance for the understanding of pain processing in healthy volunteers, but putatively even more so in patients with major depressive disorder. Moreover, our results might indicate that central nervous structures involved in the affective domain or cognitive domain of pain processing might be involved in the perception of the illusion.

  13. Reduced expression of pain mediators and pain sensitivity in amyloid precursor protein over-expressing CRND8 transgenic mice.

    PubMed

    Shukla, M; Quirion, R; Ma, W

    2013-10-10

    β-Amyloid (Aβ) peptides are derived from the sequential cleavage of the amyloid precursor protein (APP). They are enriched in plaques present in Alzheimer's brains and thus play important roles in the pathogenesis of this disease. APP is also known to be expressed in the neurons of dorsal root ganglion (DRG) and contributes to neuronal survival and axonal growth during development. However, whether APP and Aβ peptides are involved in nociception and pathological pain states is mostly unknown. In the present study, we have used behavioral, biochemical and morphological approaches to address this issue in both adult rats and APP over-expressing CRND8 transgenic mice. We observed that the Aβ peptide (17-24) was predominantly expressed in small-sized DRG neurons of rats. Following intraplantar (i.pl.) injection of complete Freud's adjuvant (CFA), the levels of APP and Aβ peptides were significantly reduced in the ipsilateral lumbar 4-6 rat DRG. In 3-, 12- and 24-month-old CRND8 mice, pain sensitivity in response to heat and mechanical stimulation was significantly dampened compared to their age-matched wild-type littermates. In parallel with reduced pain sensitivity, the expression of pain mediators such as substance P, calcitonin gene-related peptide and transient receptor potential vanilloid-1 was significantly reduced in L4-6 DRG of CRND8 mice. Although i.pl. injection of CFA induced a rather similar pattern of inflammatory pain in 3-month-old CRND8 mice and their wild-type littermates, recovery from inflammatory pain seemed faster in 12-month-old CRND8 mice than wild-type mice. These findings suggest that APP and Aβ peptides suppress both nociception and inflammatory pain and are likely involved in blunt pain perception of Alzheimer's patients in clinical settings.

  14. Genetic predictors for acute experimental cold and heat pain sensitivity in humans

    PubMed Central

    Kim, H; Mittal, D P; Iadarola, M J; Dionne, R A

    2006-01-01

    Background The genetic contribution to pain sensitivity underlies a complex composite of parallel pain pathways, multiple mechanisms, and diverse inter‐individual pain experiences and expectations. Methods Variations for genes encoding receptors related to cold and heat sensation, such as transient receptor potential A subtype 1 (TRPA1), M subtype 8 (TRPM8), V subtype 1 (TRPV1), δ opioid receptor subtype 1 (OPRD1), catechol O‐methyltransferase (COMT), and fatty acid amide hydrolyase (FAAH), were investigated in four major ethnic populations. Results We defined 13 haplotype blocks in European Americans, seven blocks in African Americans, seven blocks in Hispanic subjects, and 11 blocks in Asian Americans. Further study in European American subjects found significant associations between short duration cold pain sensitivity and variations in TRPA1, COMT, and FAAH in a gender dependent manner. Our observations demonstrate that genetic variations in TRPA1, COMT, and FAAH contribute gender specifically to individual variations in short duration cold pain sensitivity in a European American cohort. Conclusions The effects of TRPA1 variations on experimental short duration heat pain sensitivity may contribute to inter‐individual variation in pain sensitivity in humans. PMID:16882734

  15. Muscle Trigger Points and Pressure Pain Sensitivity Maps of the Feet in Women with Fibromyalgia Syndrome.

    PubMed

    Tornero-Caballero, Maria C; Salom-Moreno, Jaime; Cigarán-Méndez, Margarita; Morales-Cabezas, Matilde; Madeleine, Pascal; Fernández-de-Las-Peñas, César

    2016-10-01

    OBJECTIVE : To investigate the presence of trigger points (TrPs) in feet musculature and topographical pressure sensitivity maps of the feet as well as the relationship between TrPs, pressure pain maps, and clinical variables in women with fibromyalgia (FMS). METHODS : Fifty-one FMS women and 24 comparable healthy women participated. TrPs within the flexor hallucis brevis, adductor hallucis, dorsal interossei, extensor digitorum brevis, and quadratus plantae, as well as external and internal gastrocnemius, were explored. Pressure pain thresholds (PPTs) were assessed in a blind manner over seven locations on each foot. Topographical pressure sensitivity maps of the plantar region were generated using the averaged PPT of each location. RESULTS : The prevalence rate of foot pain was 63% (n = 32). The number of active TrPs for each FMS woman with foot pain was 5 ± 1.5 without any latent TrPs. Women with FMS without foot pain and healthy controls had only latent TrPs (2.2 ± 0.8 and 1.5 ± 1.3, respectively). Active TrPs in the flexor hallucis brevis and adductor hallucis muscles were the most prevalent. Topographical pressure pain sensitivity maps revealed that FMS women with foot pain had lower PPT than FMS women without pain and healthy controls, and higher PPT on the calcaneus bone (P < 0.001). CONCLUSIONS : The presence of foot pain in women with FMS is high. The referred pain elicited by active TrPs in the foot muscles reproduced the symptoms in these patients. FMS women suffering foot pain showed higher pressure hypersensitivity in the plantar region than those FMS women without pain.

  16. Endogenous Opioids May Buffer Effects of Anger Arousal on Sensitivity to Subsequent Pain

    PubMed Central

    Burns, John W.; Bruehl, Stephen; Chung, Ok Y.; Magid, Edward; Chont, Melissa; Goodlad, James K.; Gilliam, Wesley; Matsuura, Justin; Somar, Kristin

    2014-01-01

    Evidence suggests that anger and pain are related, yet it is not clear by what mechanisms anger may influence pain. We have proposed that effects of anger states and traits on pain sensitivity are partly opioid-mediated. In this study, we tested the extent to which analgesic effects of acute anger arousal on subsequent pain sensitivity were opioid-mediated by subjecting healthy participants to anger-induction and pain either under opioid blockade (oral naltrexone) or placebo. Participants were 160 healthy individuals. A double-blind, placebo-controlled, between-subjects opioid blockade design was used, with participants assigned randomly to one of two Drug conditions (placebo or naltrexone), and to one of two Task Orders (anger-induction followed by pain or vice versa). Results of ANOVAs showed significant Drug Condition × Task Order interactions for sensory pain ratings (MPQ-Sensory) and angry and nervous affect during pain-induction, such that participants who underwent anger-induction prior to pain while under opioid blockade (naltrexone) reported more pain, and anger and nervousness than those who underwent the tasks in the same order, but did so on placebo. Results suggest that for people with intact opioid systems, acute anger arousal may trigger endogenous opioid release that reduces subsequent responsiveness to pain. Conversely, impaired endogenous opioid function, such as that found among some chronic pain patients, may leave certain people without optimal buffering from the otherwise hyperalgesic affects of anger arousal, and so may lead to greater pain and suffering following upsetting or angry events. PMID:19682793

  17. 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

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

    PubMed

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

    2015-10-01

    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.

  19. [Pain sensitivity changes in schizophrenic patients and animal models--Part II].

    PubMed

    Tuboly, Gábor; Horváth, Gyöngyi

    2009-05-30

    Diminished pain sensitivity in schizophrenic patients has been reported for more than 50 years, however little is known about the substrate and the basic mechanisms underlying altered pain sensitivity in this disease, therefore, relevant animal models are of decisive importance in the study of psychiatric diseases. The authors report a review consisting of two parts focusing on pain sensitivity changes in patients and in different animal models which proved the eligibility as schizophrenia models and pain sensitivities have also been determined. The second part of this article analyzed the results regarding knock out mice as schizophrenia models. These data proved that several genes have significant role in the pathomechanism of schizophrenia; therefore deficiency in one gene does not produce animals showing all signs of this disease. As regards the pain sensitivity changes, only a few data are available with controversial results. Data originated from complex chronic animal models indicate that they might be more adequate methods for studying the mechanisms of schizophrenia including the pain-sensitivity changes.

  20. 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.

  1. Relationship between self-reported pain sensitivity and pain after total knee arthroplasty: a prospective study of 71 patients 8 weeks after a standardized fast-track program

    PubMed Central

    Valeberg, Berit T; Høvik, Lise H; Gjeilo, Kari H

    2016-01-01

    Background and purpose This was a prospective cohort study assessing data from 71 adult patients undergoing total knee arthroplasty (TKA) following a standardized fast-track program between January and July 2013. The objective was to examine the relationship between self-rated pain sensitivity, as measured by the Pain Sensitivity Questionnaire (PSQ), and postoperative pain after TKA. Methods The baseline questionnaires, PSQ and Brief Pain Inventory, were given to the patients for self-administration at the presurgical evaluation (1–2 weeks prior to surgery). The follow-up questionnaire, Brief Pain Inventory, was administered at the first follow-up, 8 weeks after surgery. Results A statistically significant association was found between average preoperative pain and average pain 8 weeks after surgery (P=0.001). The PSQ-minor was statistically significantly associated with average pain only for patients younger than 70 years (P=0.03). Interpretation This is the first study to examine the relationship between pain sensitivity measured by PSQ and postoperative pain in patients after TKA. We found that a lower score on the PSQ-minor was statistically significantly associated with patients’ pain 8 weeks after TKA surgery, but only for younger patients. Further research is needed to explore whether the PSQ could be a useful screening tool for patients’ pain sensitivity in clinical settings. PMID:27660489

  2. Differential changes in gingival somatosensory sensitivity after painful electrical tooth stimulation.

    PubMed

    Baad-Hansen, Lene; Lu, Shengyi; Kemppainen, Pentti; List, Thomas; Zhang, Zhenting; Svensson, Peter

    2015-04-01

    We aimed to evaluate the effect of painful tooth stimulation on gingival somatosensory sensitivity of healthy volunteers in a randomized, controlled design. Thirteen healthy volunteers (six women, seven men; 28.4 ± 5.0 years) were included for two experimental sessions of electrical tooth stimulation: painful tooth stimulation and tooth stimulation below the sensory threshold (control). Eight of the human subjects participated in a third session without tooth stimulation. In all sessions, the somatosensory sensitivity of the gingiva adjacent to the stimulated tooth was evaluated with a standardized battery of quantitative sensory tests (QST) before, immediately after and 30 min after tooth stimulation. Painful tooth stimulation evoked significant decreases in warmth and heat pain thresholds (P < 0.001) as well as pressure pain thresholds (increased sensitivity) (P = 0.024) and increases in mechanical detection thresholds (decreased sensitivity) (P < 0.050). Similar thermal threshold changes (P < 0.019) but no mechanical changes were found after tooth stimulation below the sensory threshold (P > 0.086). No QST changes were detected in the session without tooth stimulation (P > 0.060). In conclusion, modest increased gingival sensitivity to warmth, painful heat and pressure stimuli as well as desensitization to non-painful mechanical stimulation were demonstrated after tooth stimulation. This suggests involvement of competing heterotopic facilitatory and inhibitory mechanisms. Furthermore, stimulation below the sensory threshold induced similar thermal sensitization suggesting the possibility of activation of axon-reflex-like mechanisms even at intensities below the perception threshold. These findings may have implications for interpretation of somatosensory results in patients with chronic intraoral pain.

  3. Alexithymia and anxiety sensitivity in patients with non-cardiac chest pain.

    PubMed

    White, Kamila S; McDonnell, Cassandra J; Gervino, Ernest V

    2011-12-01

    The aim of this study was to examine independent and combined influences of alexithymia and anxiety sensitivity on chest pain and life interference in patients with non-cardiac chest pain (NCCP). Theories of NCCP posit a central role for emotion in the experience of chest pain, however, studies have not examined how alexithymia characterized by a difficulty identifying or verbalizing emotions, may influence this relationship. This study examined 231 patients (56% females, M age=50 years) with chest pain seeking cardiac evaluation, who showed no abnormalities during exercise tolerance testing. Forty percent (40%) scored at or above the moderate range of alexithymia. Whereas health care utilization was associated with elevated alexithymia among men, health care utilization was associated with elevated anxiety sensitivity among women. Hierarchical regression analyses revealed that alexithymia and anxiety sensitivity were both uniquely and independently associated with pain severity and life interference due to pain. Alexithymia-pain links were stronger for men compared to women. Secondary analyses conducted with a subsample suggest that alexithymia may be increasingly stable over time (i.e., 18-month follow-up). Findings are largely congruent with theoretical models of NCCP showing that personality and emotional factors are important in this medically unexplained syndrome.

  4. A systematic literature review of 10 years of research on sex/gender and pain perception - part 2: do biopsychosocial factors alter pain sensitivity differently in women and men?

    PubMed

    Racine, Mélanie; Tousignant-Laflamme, Yannick; Kloda, Lorie A; Dion, Dominique; Dupuis, Gilles; Choinière, Manon

    2012-03-01

    This systematic review summarizes the results of 10 years of laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian to access multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The second set of results presented in this review (129 articles) examined various biopsychosocial factors that may contribute to differences in pain sensitivity between healthy women and men. The results revealed that the involvement of hormonal and physiological factors is either inconsistent or absent. Some studies suggest that temporal summation, allodynia, and secondary hyperalgesia may be more pronounced in women than in men. The evidence to support less efficient endogenous pain inhibitory systems in women is mixed and does not necessarily apply to all pain modalities. With regard to psychological factors, depression may not mediate sex differences in pain perception, while the role of anxiety is ambiguous. Cognitive and social factors appear to partly explain some sex-related differences. Finally, past individual history may be influential in female pain responses. However, these conclusions must be treated with much circumspection for various methodological reasons. Furthermore, some factors/mechanisms remain understudied in the field. There is also a need to assess and improve the ecological validity of findings from laboratory studies on healthy subjects, and perhaps a change of paradigm needs to be considered at this point in time to better understand the factors that influence the experience of women and men who suffer from acute or chronic pain.

  5. The genetic mediation of individual differences in sensitivity to pain and its inhibition

    PubMed Central

    Mogil, Jeffrey S.

    1999-01-01

    The underlying bases of the considerable interindividual variability in pain-related traits are starting to be revealed. Although the relative importance of genes versus experience in human pain perception remains unclear, rodent populations display large and heritable differences in both nociceptive and analgesic sensitivity. The identification and characterization of particularly divergent populations provides a powerful initial step in the genetic analysis of pain, because these models can be exploited to identify genes contributing to the behavior-level variability. Ultimately, DNA sequence differences representing the differential alleles at pain-relevant genes can be identified. Thus, by using a combination of “top-down” and “bottom-up” strategies, we are now able to genetically dissect even complex biological traits like pain. The present review summarizes the current progress toward these ends in both humans and rodents. PMID:10393892

  6. Pressure Pain Sensitivity in Patients With Suspected Opioid-Induced Hyperalgesia

    PubMed Central

    Wasserman, Ronald A.; Hassett, Afton L.; Harte, Steven E.; Goesling, Jenna; Malinoff, Herbert L.; Berland, Daniel W.; Zollars, Jennifer; Moser, Stephanie E.; Brummett, Chad M.

    2015-01-01

    Background and Objectives This study was designed to test whether a brief quantitative sensory testing (QST) assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia. Methods Twenty patients on long-term opioid therapy with suspected opioid-induced hyperalgesia were recruited along with and 20 healthy controls. Pressure pain threshold, Pain50, a measure of intermediate suprathreshold pressure pain sensitivity, and tolerance levels, were evaluated. As a secondary outcome, changes in pressure pain sensitivity following intravenous administration of placebo (saline) and fentanyl (1.5 μg/kg) were assessed. Results There were no significant differences in pain measures between healthy controls and patients. However, there was an association between higher doses of opioids and having a lower pain tolerance (r= -0.46, P=0.041) and lower Pain50 (r=-0.46, P = 0.044), which was consistent with the hypothesis. Patients on >100 mg oral morphine equivalents (OME) displayed decreased pressure pain tolerance compared to patients taking <100 mg OME (P = 0.042). In addition, male patients showed a hyperalgesic response to fentanyl administration, which was significant for the Pain50 measure (P=0.002). Conclusions Whereas there were no differences between patients suspected of having opioid-induced hyperalgesia and the healthy controls, the finding that higher doses of opioids were associated with more sensitivity suggests that dose might be an important factor in the development of hyperalgesia. In addition, male patients demonstrated a hyperalgesic response after a bolus of fentanyl. Future studies are needed to develop better diagnostics for detecting hyperalgesia in the clinical setting. PMID:26469365

  7. 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

  8. Sensitization of nociceptive spinal neurons contributes to pain in a transgenic model of sickle cell disease.

    PubMed

    Cataldo, Giuseppe; Rajput, Sugandha; Gupta, Kalpna; Simone, Donald A

    2015-04-01

    Chronic pain is a major characteristic feature of sickle cell disease (SCD). The refractory nature of pain and the development of chronic pain syndromes in many patients with SCD suggest that central neural mechanisms contribute to pain in this disease. We used HbSS-BERK sickle mice, which show chronic features of pain similar to those observed in SCD, and determined whether sensitization of nociceptive neurons in the spinal cord contributes to pain and hyperalgesia in SCD. Electrophysiological recordings of action potential activity were obtained from single identified dorsal horn neurons of the spinal cord in anesthetized mice. Compared with control HbAA-BERK mice, nociceptive dorsal horn neurons in sickle mice exhibited enhanced excitability as evidenced by enlarged receptive fields, increased rate of spontaneous activity, lower mechanical thresholds, enhanced responses to mechanical stimuli, and prolonged afterdischarges following mechanical stimulation. These changes were accompanied by increased phosphorylation of mitogen-activated protein kinases (MAPKs) in the spinal cord that are known to contribute to neuronal hyperexcitability, including c-Jun N-terminal kinase (JNK), p44/p42 extracellular signaling-regulated kinase (ERK), and p38. These findings demonstrate that central sensitization contributes to pain in SCD.

  9. Endogenous Opioid-Masked Latent Pain Sensitization: Studies from Mouse to Human

    PubMed Central

    Dahl, Jørgen B.; Werner, Marianne; Taylor, Bradley K.; Werner, Mads U.

    2015-01-01

    Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P < 0.001) and secondary hyperalgesia (P < 0.001) by naloxone (0.3–10 mg/kg), 168 hrs after the induction of MHI. Forward-translating the dose data to a human MHI model (n = 12) we could show that LS does indeed occur after naloxone 2 mg/kg, 168 hrs after a MHI. Our previous unsuccessful efforts to demonstrate unmasking of LS in humans are thus likely explained by an insufficient naloxone dose (0.021 mg/kg). However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future exploratory studies in humans should prioritize inclusion of “high-sensitizers” prone to develop LS and use post-surgical models to elucidate markers of vulnerability to chronic postsurgical pain. Trial Registration EudraCT 2012-005663-27 PMID:26305798

  10. 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.

  11. 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.

  12. Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain.

    PubMed

    Starkweather, Angela R; Heineman, Amy; Storey, Shannon; Rubia, Gil; Lyon, Debra E; Greenspan, Joel; Dorsey, Susan G

    2016-02-01

    Quantitative sensory testing can be used to assess peripheral and central sensitization; important factors that contribute to the individual's experience of pain and disability. Many studies use quantitative sensory testing in patients with low back pain to detect alterations in pain sensitivity, however, because investigators employ different protocols, interpretation of findings across studies can become problematic. The purpose of this article is to propose a standardized method of testing peripheral and central pain sensitization in patients with low back pain. Video clips are provided to demonstrate correct procedures for measuring the response to experimental pain using mechanical, thermal and pressure modalities. As nurse researchers and clinicians increase utilization of quantitative sensory testing to examine pain phenotypes, it is anticipated that more personalized methods for monitoring the trajectory of low back pain and response to treatment will improve outcomes for this patient population.

  13. Dental anxiety in relation to neuroticism and pain sensitivity. A twin study.

    PubMed

    Vassend, Olav; Røysamb, Espen; Nielsen, Christopher S

    2011-03-01

    Predisposing personality traits as well as heightened pain sensitivity and fear of pain have been hypothesized as central factors in the development of dental anxiety. The aim of the study was to estimate the heritability of dental anxiety, and to investigate the genetic and environmental sources of covariance between dental anxiety on one hand, and pain sensitivity and the neuroticism trait on the other. A sample comprising 188 twins, aged 23-35 years (53 monozygotic and 39 dizygotic twin pairs, and 4 single twins whose co-twin did not participate), was included in the study. Measures of dental anxiety and personality were obtained using Corah's Dental Anxiety Scale and the NEO Personality Inventory Revised, respectively. Heat pain and cold pressor pain sensitivity were assessed using standard pain testing procedures. Bivariate Cholesky models were employed to decompose the correlations between phenotypes into genetic and environmental factors. Using models with common additive genetic (A) and individual-specific environmental (E) factors, moderate heritability (i.e., .41) for dental anxiety was demonstrated. Virtually all of the phenotypic correlation between neuroticism and dental anxiety could be accounted for by A. Furthermore, a substantial part of the variance in dental anxiety was due to specific genetic and individual environmental influences unrelated to neuroticism. The phenotypic correlations between dental anxiety and the pain sensitivity indices were close to zero. Thus, while neuroticism and dental anxiety share a sizeable proportion of genetic (but not environmental) risk factors, the results also suggest that these two attributes are distinct entities with overlapping, but not identical, etiologies.

  14. 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.

  15. Changes in Pain Sensitivity following Spinal Manipulation: a Systematic Review and Meta-Analysis

    PubMed Central

    Coronado, Rogelio A; Gay, Charles W.; Bialosky, Joel E.; Carnaby, Giselle D.; Bishop, Mark D.; George, Steven Z.

    2012-01-01

    Spinal manipulation (SMT) is commonly used for treating individuals experiencing musculoskeletal pain. The mechanisms of SMT remain unclear; however, pain sensitivity testing may provide insight into these mechanisms. The purpose of this systematic review is to examine the literature on the hypoalgesic effects of SMT on pain sensitivity measures and to quantify these effects using meta-analysis. We performed a systematic search of articles using CINAHL, MEDLINE, PsycINFO, and SPORTDiscus from each databases’ inception until May 2011. We examined methodological quality of each study and generated pooled effect size estimates using meta-analysis software. Of 997 articles identified, 20 met inclusion criteria for this review. Pain sensitivity testing used in these studies included chemical, electrical, mechanical, and thermal stimuli applied to various anatomical locations. Meta-analysis was appropriate for studies examining the immediate effect of SMT on mechanical pressure pain threshold (PPT). SMT demonstrated a favorable effect over other interventions on increasing PPT. Subgroup analysis showed a significant effect of SMT on increasing PPT at the remote sites of stimulus application supporting a potential central nervous system mechanism. Future studies of SMT related hypoalgesia should include multiple experimental stimuli and test at multiple anatomical sites. PMID:22296867

  16. A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients.

    PubMed

    White, Hillary D; Robinson, Thomas D

    2015-08-01

    Fibromyalgia is a diffuse chronic pain condition that occurs predominantly in women and may be under-reported in men. Symptoms include a loss of feeling of well-being and generalized widespread flu-like muscle aches and pain that fail to resolve due to central sensitization of nociceptive neurons. It has commonalities with a myriad of other chronic pain conditions which include PTSD, "Gulf War Syndrome", and various stress-induced conditions caused, for example, by viral infection, emotional or physical stress, trauma, combat, accident or surgery. It is not understood why some individuals are susceptible to this condition and others are not. White et al., elsewhere in this issue, present a clinical feasibility study designed to test the hypothesis that 1) low or deficient testosterone serum levels are linked to a high risk for an inflamed nociceptive nervous system and resultant chronic pain states, and 2) a testosterone transdermal gel applied once a day by fibromyalgia patients can be an effective therapeutic against chronic pain. Here, a short profile of fibromyalgia is provided along with a brief summary of best practices currently recommended by clinical specialists. The link between testosterone and pain is then discussed, with an overview of scientific studies that lay the foundation for testosterone as a possible important additional therapeutic that has the potential to be safely administered and effective but also avoid the adverse effects of other therapeutics. Finally, novel mechanisms by which testosterone therapy is likely to down-modulate pain signaling are proposed.

  17. Five-factor personality traits and pain sensitivity: a twin study.

    PubMed

    Vassend, Olav; Røysamb, Espen; Nielsen, Christopher S

    2013-05-01

    Factors underlying individual differences in pain responding are incompletely understood, but are likely to include genetic influences on basal pain sensitivity in addition to demographic characteristics such as age, sex, and ethnicity, and psychological factors including personality. This study sought to explore the relationship between personality traits and experimental pain sensitivity, and to determine to what extent the covariances between these phenotypes are mediated by common genetic and environmental factors. A sample composed of 188 twins, aged 23 to 35years, was included in the study. Heat pain intensity (HPI) and cold-pressor pain intensity (CPI) ratings were obtained using standardized pain testing procedures, and personality traits were assessed with the NEO Personality Inventory, Revised. Associations between personality and the pain sensitivity indices were examined using zero-order correlations and generalized estimating equations. Bivariate Cholesky models were used in the biometric analyses. The most robust finding was a significant phenotypic association between CPI and the personality facets Impulsiveness (a facet of Neuroticism) and Excitement-Seeking (a facet of Extraversion), and estimates of the genetic correlation were .37 (P<.05) and .43 (P<.05), respectively. In contrast, associations between HPI and personality seemed weak and unstable, but a significant effect of Angry Hostility (a facet of Neuroticism) emerged in generalized estimating equations analysis. Although the genetic correlation between these phenotypes was essentially zero, a weak but significant individual-specific environmental correlation emerged (re=.21, P<.05). Taken together, these findings suggest that CPI is more consistently related to personality dispositions than HPI, both phenotypically and genetically.

  18. Abnormal Pressure Pain, Touch Sensitivity, Proprioception, and Manual Dexterity in Children with Autism Spectrum Disorders

    PubMed Central

    Riquelme, Inmaculada; Hatem, Samar M.

    2016-01-01

    Children with autism spectrum disorders (ASD) often display an abnormal reactivity to tactile stimuli, altered pain perception, and lower motor skills than healthy children. Nevertheless, these motor and sensory deficits have been mostly assessed by using clinical observation and self-report questionnaires. The present study aims to explore somatosensory and motor function in children with ASD by using standardized and objective testing procedures. Methods. Tactile and pressure pain thresholds in hands and lips, stereognosis, proprioception, and fine motor performance of the upper limbs were assessed in high-functioning children with ASD (n = 27) and compared with typically developing peers (n = 30).  Results. Children with ASD showed increased pain sensitivity, increased touch sensitivity in C-tactile afferents innervated areas, and diminished fine motor performance and proprioception compared to healthy children. No group differences were observed for stereognosis. Conclusion. Increased pain sensitivity and increased touch sensitivity in areas classically related to affective touch (C-tactile afferents innervated areas) may explain typical avoiding behaviors associated with hypersensitivity. Both sensory and motor impairments should be assessed and treated in children with ASD. PMID:26881091

  19. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26690466

  1. 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.

  2. The Comparative Effects of Spinal and Peripheral Thrust Manipulation and Exercise on Pain Sensitivity and the Relation to Clinical Outcome: A Mechanistic Trial Using a Shoulder Pain Model

    PubMed Central

    Coronado, Rogelio A.; Bialosky, Joel E.; Bishop, Mark D.; Riley, Joseph L.; Robinson, Michael E.; Michener, Lori A.; George, Steven Z.

    2016-01-01

    STUDY DESIGN Single-blind randomized trial. OBJECTIVES To compare the effects of cervical and shoulder thrust manipulation (TM) and exercise on pain sensitivity, and to explore associations with clinical outcomes in patients with shoulder pain. BACKGROUND Experimental studies indicate that spinal TM has an influence on central pain processes, supporting its application for treatment of extremity conditions. Direct comparison of spinal and peripheral TM on pain sensitivity has not been widely examined. METHODS Seventy-eight participants with shoulder pain (36 female; mean ± SD age, 39.0 ± 14.5 years) were randomized to receive 3 treatments of cervical TM (n = 26), shoulder TM (n = 27), or shoulder exercise (n = 25) over 2 weeks. Twenty-five healthy participants (13 female; mean ± SD age, 35.2 ± 11.1 years) were assessed to compare pain sensitivity with that in clinical participants at baseline. Primary outcomes were changes in local (eg, shoulder) and remote (eg, tibialis anterior) pressure pain threshold and heat pain threshold occurring over 2 weeks. Secondary outcomes were shoulder pain intensity and patient-rated function at 4, 8, and 12 weeks. Analysis-of-variance models and partial-correlation analyses were conducted to examine comparative effects and the relationship between measures. RESULTS At baseline, clinical participants demonstrated lower local (mean difference, −1.63 kg; 95% confidence interval [CI]: −2.40, −0.86) and remote pressure pain threshold (mean difference, −1.96 kg; 95% CI: −3.09, −0.82) and heat pain threshold (mean difference, −1.15°C; 95% CI: −2.06, −0.24) compared to controls, suggesting enhanced pain sensitivity. Following intervention, there were no between-group differences in pain sensitivity or clinical outcome (P>.05). However, improvements were noted, regardless of intervention, for pressure pain threshold (range of mean differences, 0.22–0.32 kg; 95% CI: 0.03, 0.43), heat pain threshold (range of mean

  3. Genotype-dependence of gabapentin and pregabalin sensitivity: the pharmacogenetic mediation of analgesia is specific to the type of pain being inhibited.

    PubMed

    Chesler, Elissa J; Ritchie, Jennifer; Kokayeff, Anna; Lariviere, William R; Wilson, Sonya G; Mogil, Jeffrey S

    2003-12-01

    The antiepileptic drug, gabapentin, and another structurally related compound, pregabalin, are increasingly employed in the pharmacotherapy of chronic pain states, although their primary mechanism of action remains a topic of active study. A genomic approach to the study of these drugs may elucidate their potentially novel mechanisms. We examined the heritability of sensitivity to analgesia from gabapentin and pregabalin as a precursor to linkage mapping efforts. Accordingly, 11 inbred mouse strains were tested for inhibition of nociception by gabapentin or pregabalin (50-300 mg/kg, i.p.) in two different preclinical assays of inflammatory pain, the formalin test (5% formalin; 20 microl) and zymosan thermal hyperalgesia on the paw-withdrawal test (3 mg/ml zymosan; 20 microl). Significant strain-dependence of drug action was noted in each case, indicating that sensitivity to these analgesics is heritable. Furthermore, the pattern of strain sensitivities to gabapentin and pregabalin were mostly similar, supporting the notion that they act via similar genetic and physiological mechanisms. However, there was virtually no correlation between strain sensitivities to pregabalin inhibition of formalin nociception and zymosan thermal hyperalgesia. In light of previous data from our laboratory and others regarding morphine analgesia, we now establish and empirically demonstrate the general principle that pharmacogenetic mechanisms underlying analgesic sensitivity are specific to the type of pain being inhibited. This has considerable implications for ongoing pharmacogenetic investigations and, more generally, for the choices of preclinical models of pain used in drug development.

  4. Sleep, pain catastrophizing and central sensitization in knee osteoarthritis patients with and without insomnia

    PubMed Central

    Campbell, Claudia M.; Buenaver, Luis F.; Finan, Patrick; Bounds, Sara C.; Redding, Mary; McCauley, Lea; Robinson, Mercedes; Edwards, Robert R.; Smith, Michael T.

    2015-01-01

    Objectives: Osteoarthritis, a chronic degenerative joint disorder, is characterized by joint pain. Emerging research demonstrates that a significant number of patients evidence central sensitization (CS), a hyper-excitability in nociceptive pathways, which is known to amplify and maintain clinical pain. The clinical correlates of CS in OA, however, are poorly understood. Insomnia is prevalent in older adults with OA and recent experiments suggest associations between poor sleep and measures of CS. Catastrophizing, a potent predictor of pain outcomes has also been associated with CS, but few studies have investigated possible interactions between catastrophizing, sleep and CS. Methods: We conducted a case controlled study of 4 well characterized groups of adults with insomnia and/or knee osteoarthritis. A total of 208 participants completed multimodal sleep assessments (questionnaire, diary, actigraphy, polysmnography) and extensive evaluation of pain using clinical measures and quantitative sensory testing to evaluate associations between CS, catastrophizing and insomnia. Descriptive characterization of each measure is presented, with specific focus on sleep efficiency and CS. Results: The KOA-Insomnia group demonstrated the greatest degree of CS compared to controls. In the overall sample, we found that catastrophizing moderated the relationship between sleep efficiency and CS. Specifically those with low sleep efficiency and high catastrophizing scores reported increased levels of CS. In addition, CS was significantly associated with increased clinical pain. Conclusions: These findings highlight the importance of assessing sleep efficiency, CS and catastrophizing in chronic pain patients and have important clinical implications for treatment planning. PMID:26041510

  5. Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations.

    PubMed

    Dworkin, Robert H; Turk, Dennis C; Peirce-Sandner, Sarah; Burke, Laurie B; Farrar, John T; Gilron, Ian; Jensen, Mark P; Katz, Nathaniel P; Raja, Srinivasa N; Rappaport, Bob A; Rowbotham, Michael C; Backonja, Misha-Miroslav; Baron, Ralf; Bellamy, Nicholas; Bhagwagar, Zubin; Costello, Ann; Cowan, Penney; Fang, Weikai Christopher; Hertz, Sharon; Jay, Gary W; Junor, Roderick; Kerns, Robert D; Kerwin, Rosemary; Kopecky, Ernest A; Lissin, Dmitri; Malamut, Richard; Markman, John D; McDermott, Michael P; Munera, Catherine; Porter, Linda; Rauschkolb, Christine; Rice, Andrew S C; Sampaio, Cristina; Skljarevski, Vladimir; Sommerville, Kenneth; Stacey, Brett R; Steigerwald, Ilona; Tobias, Jeffrey; Trentacosti, Ann Marie; Wasan, Ajay D; Wells, George A; Williams, Jim; Witter, James; Ziegler, Dan

    2012-06-01

    A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence-based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety.

  6. Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain

    PubMed Central

    Han, Liang; Li, Man; Li, Zhe; LaVinka, Pamela Colleen; Sun, Shuohao; Tang, Zongxiang; Park, Kyoungsook; Caterina, Michael J.; Ren, Ke; Dubner, Ronald; Wei, Feng; Dong, Xinzhong

    2014-01-01

    SUMMARY The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal new central mechanisms facilitating central terminal sensitization underlying chronic pain. PMID:24462040

  7. Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.

    PubMed

    Kim, Yu Shin; Chu, Yuxia; Han, Liang; Li, Man; Li, Zhe; Lavinka, Pamela Colleen; Sun, Shuohao; Tang, Zongxiang; Park, Kyoungsook; Caterina, Michael J; Ren, Ke; Dubner, Ronald; Wei, Feng; Dong, Xinzhong

    2014-02-19

    The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal central mechanisms facilitating central terminal sensitization underlying chronic pain.

  8. CAPSAICIN-SENSITIVE SENSORY NERVE FIBERS CONTRIBUTE TO THE GENERATION AND MAINTENANCE OF SKELETAL FRACTURE PAIN

    PubMed Central

    Jimenez-Andrade, Juan Miguel; Bloom, Aaron P.; Mantyh, William G.; Koewler, Nathan J.; Freeman, Katie T.; Delong, David; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2009-01-01

    Although skeletal pain can have a marked impact on a patient’s functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15–16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP+) sensory nerve fibers, but not 200 kD neurofilament H positive (NF200+) sensory nerve fibers in the periosteum. The periosteum is a thin, cellular and fibrous tissue that tightly adheres to the outer surface of all but the articulated surface of bone and appears to play a pivotal role in driving fracture pain. In animals treated with capsaicin, but not vehicle, there was a 50% reduction in the severity, but no change in the time course, of fracture-induced skeletal pain related behaviors as measured by spontaneous flinching, guarding and weight bearing. These results suggest that both capsaicin-sensitive (primarily CGRP+ C-fibers) and capsaicin-insensitive (primarily NF200+ A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain. PMID:19486928

  9. Short-term olfactory sensitization involves brain networks relevant for pain, and indicates chemical intolerance.

    PubMed

    Andersson, Linus; Claeson, Anna-Sara; Nyberg, Lars; Nordin, Steven

    2017-04-01

    Chemical intolerance is a medically unexplained affliction that implies deleterious reactions to non-toxic everyday chemical exposure. Sensitization (i.e. increased reactivity to repeated, invariant stimulation) to odorous stimulation is an important component in theoretical explanations of chemical intolerance, but empirical evidence is scarce. We hypothesized that (1) individuals who sensitize to repeated olfactory stimulation, compared with those who habituate, would express a lower blood oxygenated level dependent (BOLD) response in key inhibitory areas such as the rACC, and higher signal in pain/saliency detection regions, as well as primary and/or secondary olfactory projection areas; and (2) olfactory sensitization, compared with habituation, would be associated with greater self-reported chemical intolerance. Moreover, we assessed whether olfactory sensitization was paralleled by comparable trigeminal processing - in terms of perceptual ratings and BOLD responses. We grouped women from a previous functional magnetic imaging study based on intensity ratings of repeated amyl acetate exposure over time. Fourteen women sensitized to the exposure, 15 habituated, and 20 were considered "intermediate" (i.e. neither sensitizers nor habituaters). Olfactory sensitizers, compared with habituaters, displayed a BOLD-pattern in line with the hypothesis, and reported greater problems with odours in everyday life. They also expressed greater reactions to CO2 in terms of both perceived intensity and BOLD signal. The similarities with pain are discussed.

  10. Within-session sensitization and between-session habituation: a robust physiological response to repetitive painful heat stimulation.

    PubMed

    May, A; Rodriguez-Raecke, R; Schulte, A; Ihle, K; Breimhorst, M; Birklein, F; Jürgens, T P

    2012-03-01

    Habituation and sensitization are important behavioural responses to repeated exposure of painful stimuli. Whereas within-session response dynamics to nociceptive stimuli is well characterized, little is known about long-term behaviour due to repetitive nociceptive stimulation. We used a standardized longitudinal heat pain paradigm in 66 healthy participants, 21 patients with chronic low back pain and 22 patients with depression who received daily sessions of 60 suprathreshold heat stimuli (48 °C each) for eight consecutive days. All three groups showed the same response: Repeated painful stimulation over several days resulted in substantially decreased pain ratings to identical painful stimuli. The decreased perception of pain over time was associated with a very robust increase in pain ratings in each single pain session, i.e., all participants sensitized within sessions and habituated between sessions. This uniform pattern was equally present in all examined groups. Chronic pain and depression do not seem to interfere with short-term sensitization and long-term habituation in this model of repetitive phasic heat pain.

  11. Repeated amphetamine treatment alters spinal magnetic resonance signals and pain sensitivity in mice.

    PubMed

    Lei, Bing-Hsuan; Chen, Jyh-Horng; Yin, Hsiang-Shu

    2014-11-07

    Manganese-enhanced magnetic resonance imaging (MEMRI) has been extensively used in studying the structural and functional features of the central nervous system (CNS). Divalent manganese ion (Mn(2+)) not only enhances MRI contrast, but also enters cells via voltage-gated calcium channels or ionotropic glutamate receptors, which represents an index of neural activities. In the current mouse model, following the repeated amphetamine (Amph) treatment, a reduction of reactivity to thermal pain stimulus was noticed. Since the spinal dorsal horn is the first relay station for pain transmission in CNS, we examined the changes of neural activity in the dorsal spinal cord, particularly the superficial dorsal horn, by analyzing manganese-enhanced T1-weighted MR images (T1WIs). Our data revealed a temporal correlation between reduced pain sensitivity and increased MEMR signals in the spinal dorsal horn subsequent to repeated Amph treatments.

  12. Age-related differences in conditioned pain modulation of sensitizing and desensitizing trends during response dependent stimulation.

    PubMed

    Naugle, Kelly M; Cruz-Almeida, Yenisel; Vierck, Charles J; Mauderli, Andre P; Riley, Joseph L

    2015-08-01

    The current study evaluated age differences in conditioned pain modulation using a test stimulus that provided the opportunity to evaluate changes in heat pain sensitivity, sensitization, and desensitization within the same paradigm. During this psychophysical test, pain intensity clamping uses REsponse Dependent STIMulation (REDSTIM) methodology to automatically adjust stimulus intensity to maintain a desired pain rating set-point. Specifically, stimulus intensity increases until a pre-defined pain rating (the setpoint) is exceeded, and then decreases until pain ratings fall below the setpoint, with continued increases and decreases dictated by ratings. The subjects are blinded in terms of the setpoint and stimulus intensities. Younger and older subjects completed two test sessions of two REDSTIM trials, with presentation of conditioning cold stimulation between the trials of one session but not the other. The results indicated that conditioning cold stimulation similarly decreased the overall sensitivity of younger and older subjects, as measured by the average temperature that maintained a setpoint rating of 20 (on a scale of 0-100). The conditioning stimulus also significantly enhanced sensitization following ascending stimulus progressions and desensitization following descending stimulus progressions in older subjects relative to younger subjects. Thus, older subjects experienced greater swings in sensitivity in response to varying levels of painful stimulation. These results are discussed in terms of control over pain intensity by descending central modulatory systems. These findings potentially shed new light on the central control over descending inhibition and facilitation of pain.

  13. 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

  14. 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

  15. Musculoskeletal Sensitization and Sleep: Chronic Muscle Pain Fragments Sleep of Mice without Altering Its Duration

    PubMed Central

    Sutton, Blair C.; Opp, Mark R.

    2014-01-01

    Study Objectives: 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. Design: A one month pre-clinical study was designed to determine the impact of musculoskeletal sensitization on sleep of C57BL/6J mice. Methods: 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. Results: 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. Conclusions: 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. Citation: Sutton BC

  16. Pain management standards in the eighth edition of the Guide for the Care and Use of Laboratory Animals.

    PubMed

    Carbone, Larry

    2012-05-01

    The eighth edition Guide for the Care and Use of Laboratory Animals sets standards for diverse laboratory animal care and use practices. It frames its standards as performance, engineering, and practice standards, with a strong emphasis on performance standards, allowing for multiple routes to clearly defined outcomes. Standards intended to be upheld rigorously are indicated through the use of must in the description, and those accommodating more flexibility are indicated through may and should statements. With respect to pain management standards, a fourth type of standard-the jurisdictional standard-has been prevalent through all 8 editions of the Guide. Under jurisdictional standards, specific methods and outcomes for measuring, preventing, or alleviating pain are not detailed, but the various jurisdictions of veterinarian, investigator, and IACUC are elaborated. Although data on pain management in laboratory animals has expanded greatly since the 1996 Guide, the eighth (2011) edition does not contain major new standards or guidance regarding animal pain management. Requirements for veterinary and IACUC involvement remain as in prior editions, and the duty of veterinarians and scientists to stay abreast of new developments is expected to drive refinement of animal pain management institution by institution. The current article details selected specific pain management standards in the 2011 Guide, lists topics in pain management for which the Guide does not set clear standards, and suggests possible standards for those topics.

  17. Effects of Environmental Enrichment on Thermal Sensitivity in an Operant Orofacial Pain Assay

    PubMed Central

    Rossi, Heather L.; Neubert, John K.

    2008-01-01

    Environmental enrichment reduces reactivity to stressor and could also modulate pain perception. In this study we sought to compare the effects of enriched and standard housing on temperature perception. In an operant assay, rats housed in an enriched environment exhibited significantly lower sensitivities to thermal stimuli and displayed less exploratory behavior in a rearing chamber. These findings indicate that environmental enrichment can significantly affect temperature perception, likely through stress-related mechanisms. PMID:17976833

  18. The effect of hyperthyroidism on opiate receptor binding and pain sensitivity

    SciTech Connect

    Edmondson, E.A. ); Bonnet, K.A.; Friedhoff, A.J. )

    1990-01-01

    This study was conducted to determine the effect of thyroid hormone on opiate receptor ligand-binding and pain sensitivity. Specific opiate receptor-binding was performed on brain homogenates of Swiss-Webster mice. There was a significant increase in {sup 3}H-naloxone-binding in thyroxine-fed subjects (hyperthyroid). Scatchard analysis revealed that the number of opiate receptors was increased in hyperthyroid mice (Bmax = 0.238 nM for hyperthyroid samples vs. 0.174 nM for controls). Binding affinity was unaffected (Kd = 1.54 nM for hyperthyroid and 1.58 nM for control samples). When mice were subjected to hotplate stimulation, the hyperthyroid mice were noted to be more sensitive as judged by pain aversion response latencies which were half that of control animals. After morphine administration, the hyperthyroid animals demonstrated a shorter duration of analgesia. These findings demonstrate that thyroxine increases opiate receptor number and native pain sensitivity but decreases the duration of analgesia from morphine.

  19. The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study

    PubMed Central

    2009-01-01

    Introduction Despite recent advances in anti-inflammatory therapy, rheumatoid arthritis (RA) patients continue to rate pain as a priority. The etiology of RA pain is likely multifactorial, including both inflammatory and non-inflammatory components. In this study, we examine the association between disease activity, sleep, psychiatric distress and pain sensitivity in RA. Methods Fifty-nine female RA patients completed questionnaires and underwent pressure pain threshold testing to assess hyperalgesia/allodynia at joint and non-joint sites. Blood samples were taken to measure C-reactive protein (CRP). The association between disease activity, sleep problems, psychiatric distress and pain threshold was assessed using Pearson/Spearman correlations and multivariable linear regression. Disease activity levels, sleep problems and psychiatric distress were compared between RA patients with fibromyalgia and RA patients without fibromyalgia. Results In unadjusted analyses, CRP was not correlated with pain threshold, but tender joint count was inversely correlated with pain threshold at all sites (P ≤ 0.004). Sleep problems were associated with low pain threshold at all sites (P ≤ 0.0008). Psychiatric distress was associated with low pain threshold at the wrist and thumbnail (P ≤ 0.006). In multivariable linear regression models, CRP was inversely associated with wrist pain threshold (P = 0.003). Sleep problems were inversely associated with pain threshold at all sites (P ≤ 0.01), but psychiatric distress was not. Despite differences in pain threshold, CRP levels and sleep problems between RA patients with fibromyalgia and those without fibromyalgia, associations between these variables did not change when patients with fibromyalgia were excluded. Conclusions Multivariable models are essential in analyses of pain. Among RA patients, inflammation is associated with heightened pain sensitivity at joints. In contrast, poor sleep is associated with diffuse pain

  20. High sensitivity cardiac troponin assays in the clinical laboratories.

    PubMed

    Jarolim, Petr

    2015-04-01

    Immunoassays measuring cardiac troponins I or T have become firmly established as critical tools for diagnosing acute myocardial infarction. While most contemporary assays provide adequate diagnostic performance, the increased sensitivity and precision of the new, high sensitivity assays that have already been introduced into clinical practice, provide the potential to further shorten intervals between blood draws or the time needed to detect the first significant troponin elevation. In addition to the relatively modest benefits at the diagnostic end, the high sensitivity assays and the investigational ultrasensitive cardiac troponin assays offer improvements for predicting major adverse cardiovascular events, development of heart failure or transition to end-stage kidney disease. These novel high sensitivity assays can measure troponin concentrations in 50%-100% of healthy individuals and therefore allow for the distribution of troponin values within a healthy cohort to be measured, patient's baseline troponin levels to be monitored, and clinicians to be alerted of deteriorating cardiorenal conditions. We envisage that the high sensitivity assays will become important tools for predicting each patient's risk of future adverse events and for guiding and monitoring corresponding adjustments of preventative therapeutic interventions.

  1. Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex.

    PubMed

    Geng, Kai-Wen; He, Ting; Wang, Rui-Rui; Li, Chun-Li; Luo, Wen-Jun; Wu, Fang-Fang; Wang, Yan; Li, Zhen; Lu, Yun-Fei; Guan, Su-Min; Chen, Jun

    2016-10-01

    Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether γ-aminobutyric acid A (GABAA) receptors are involved in mediating the ethanol effects, muscimol, a selective GABAA receptor agonist, or bicuculline, a selective GABAA receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABAA receptors in the mPFC of rats.

  2. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury.

    PubMed

    de la Puente, Beatriz; Nadal, Xavier; Portillo-Salido, Enrique; Sánchez-Arroyos, Ricard; Ovalle, Sergio; Palacios, Gabriel; Muro, Asunción; Romero, Luz; Entrena, José Manuel; Baeyens, José Manuel; López-García, José Antonio; Maldonado, Rafael; Zamanillo, Daniel; Vela, José Miguel

    2009-10-01

    Sigma-1 receptor (sigma(1)R) is expressed in key CNS areas involved in nociceptive processing but only limited information is available about its functional role. In the present study we investigated the relevance of sigma(1)R in modulating nerve injury-evoked pain. For this purpose, wild-type mice and mice lacking the sigma(1)R gene were exposed to partial sciatic nerve ligation and neuropathic pain-related behaviors were investigated. To explore underlying mechanisms, spinal processing of repetitive nociceptive stimulation and expression of extracellular signal-regulated kinase (ERK) were also investigated. Sensitivity to noxious heat of homozygous sigma(1)R knockout mice did not differ from wild-type mice. Baseline values obtained in sigma(1)R knockout mice before nerve injury in the plantar, cold-plate and von Frey tests were also indistinguishable from those obtained in wild-type mice. However, cold and mechanical allodynia did not develop in sigma(1)R null mice exposed to partial sciatic nerve injury. Using isolated spinal cords we found that mice lacking sigma(1)R showed reduced wind-up responses respect to wild-type mice, as evidenced by a reduced number of action potentials induced by trains of C-fiber intensity stimuli. In addition, in contrast to wild-type mice, sigma(1)R knockout mice did not show increased phosphorylation of ERK in the spinal cord after sciatic nerve injury. Both wind-up and ERK activation have been related to mechanisms of spinal cord sensitization. Our findings identify sigma(1)R as a constituent of the mechanisms modulating activity-induced sensitization in pain pathways and point to sigma(1)R as a new potential target for drugs designed to alleviate neuropathic pain.

  3. Hepatitis C virus infection and pain sensitivity in patients on methadone or buprenorphine maintenance therapy for opioid use disorders

    PubMed Central

    Tsui, Judith I.; Lira, Marlene C.; Cheng, Debbie M.; Winter, Michael R.; Alford, Daniel P.; Liebschutz, Jane M.; Mao, Jianren; Edwards, Robert R.; Samet, Jeffrey H.

    2015-01-01

    Background Patients with opioid use disorders on opioid agonist therapy (OAT) have lower pain tolerance compared to controls. While chronic viral infections such as HCV and HIV have been associated with chronic pain in this population, no studies have examined their impact on pain sensitivity. Methods We recruited 106 adults (41 uninfected controls; 40 HCV mono-infected; and 25 HCV/HIV co-infected) on buprenorphine or methadone to assess whether HCV infection (with or without HIV) was associated with increased experimental pain sensitivity and self-reported pain. The primary outcome was cold pain tolerance assessed by cold-press or test. Secondary outcomes were cold pain thresholds, wind-up ratios to repetitive mechanical stimulation (i.e., temporal summation) and acute and chronic pain. Multivariable regression models evaluated associations between viral infection status and outcomes, adjusting for other factors. Results No significant differences were detected across groups for primary or secondary outcomes. Adjusted mean cold pain tolerance was 25.7 (uninfected controls) vs. 26.8 (HCV mono-infection) vs. 25.3 (HCV/HIV co-infection) seconds (global p-value=0.93). Current pain appeared more prevalent among HCV mono-infected (93%) compared to HCV/HIV co-infected participants (76%) and uninfected controls (80%), as did chronic pain (77% v. 64% v. 61% respectively). However, differences were not statistically significant in multivariable models. Conclusion This study did not detect an association between HCV infection and increased sensitivity to pain among adults with and without HIV who were treated with buprenorphine or methadone for opioid use disorders. Results reinforce that pain and hyperalgesia are common problems in this population. PMID:26048638

  4. Usefulness of laboratory data in the management of right iliac fossa pain in adults

    PubMed Central

    Ortega-Deballon, Pablo; Ruiz De Adana-Belbel, Juan C; Hernández-Matías, Alberto; García-Septiem, Javier; Moreno-Azcoita, Mariano

    2008-01-01

    Background Inflammatory markers could be helpful in the management of patients with right iliac fossa pain, but the heterogeneity of designs and results precludes a definitive conclusion. A retrospective analysis of prospectively collected data was performed to assess the usefulness of laboratory data in the management of these patients. Patients and methods Patients with right iliac fossa pain referred to the surgeon were included. Blood samples were obtained for C-reactive protein, leukocyte, and granulocyte analysis. Clinical, surgical, and histopathologic data were collected. Analysis of inflammatory parameters was performed with logistic regression and areas under the receiver operating characteristic curve were compared. Results One hundred thirty-four patients were included. C-reactive protein increased with the severity of appendicitis and predicted accurately perforation (r2 = 0.613; P < 0.0005), showing the highest accuracy among inflammatory markers (areas under the ROC curve were 0.846, 0.753 and 0.685 for C-reactive protein, leukocyte and granulocytes, respectively; P < 0.001). Accuracy improved when C-reactive protein and leukocytes were combined (positive and negative predictive values were 93.2 percent and 92.3 percent, respectively). Conclusions C-reactive protein is a helpful marker in the management of patients with right iliac fossa pain. It increases with the evolution of the inflammatory process. Its predictive values improve in combination with the leukocyte count. A patient with normal C-reactive protein and leukocytes has a very low probability of appendicitis and should not undergo surgery. PMID:18484138

  5. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain.

    PubMed

    Dai, Yi; Wang, Shenglan; Tominaga, Makoto; Yamamoto, Satoshi; Fukuoka, Tetsuo; Higashi, Tomohiro; Kobayashi, Kimiko; Obata, Koichi; Yamanaka, Hiroki; Noguchi, Koichi

    2007-07-01

    Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation. Transient receptor potential A1 (TRPA1) is an excitatory ion channel on primary sensory nerves of pain pathway. Here, we show that a functional interaction of PAR2 and TRPA1 in dorsal root ganglion (DRG) neurons could contribute to the sensation of inflammatory pain. Frequent colocalization of TRPA1 with PAR2 was found in rat DRG neurons. PAR2 activation increased the TRPA1 currents evoked by its agonists in HEK293 cells transfected with TRPA1, as well as DRG neurons. Application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppressed this potentiation. Decrease of plasma membrane PIP(2) levels through antibody sequestration or PLC-mediated hydrolysis mimicked the potentiating effects of PAR2 activation at the cellular level. Thus, the increased TRPA1 sensitivity may have been due to activation of PLC, which releases the inhibition of TRPA1 from plasma membrane PIP(2). These results identify for the first time to our knowledge a sensitization mechanism of TRPA1 and a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.

  6. [Prognostic elements at early stapes of severe spinal cord injuries (value of pain sensitivity].

    PubMed

    Vlahovitch, B; Fuentes, J M; Choucair, Y; Orst, G; Asencio, J G; Maille, B; Verger, A C

    1975-11-01

    The prognosis in serious spinal cord injury remains difficult. The neurologist has a large number of elements at his disposal, but their reliability is uncertain. Clinical information, experimental work and recent data on medullar vascularization makes it possible to isolate diagramatically in the spinal cord a medium layer which contains the pyramidal and spino-thalamic tracts. The neighbourhood of these two fasciculi confers them a similar vulnerability to severe injury. Thus when an injured tetraplegic or paraplegic patient recovers his sensitivity to pain, he finally must recover his motor function and on the contrary, the recovery of motility is impossible without a return of pain sens. Clinical observation is in consequence of major importance as it shows that the recovery of sensitivity to pain, in the case of a patient with a serious spinal cord injury, is an argument for a favourable prognosis, whereas the recovery of an isolated tact perception does not in itself makes it possible to hope for eventual recovery of motor power.

  7. [Somatic pain sensitivity under indometacin induced gastric and small intestinal injury in rats].

    PubMed

    Iarushkina, N I; Bagaeva, T R; Filaretova, L P

    2014-01-01

    The aim was to study the effect of indometacin (IM) induced gastrointestinal injury on somatic pain sensitivity in awake rats. IM was administered at the ulcerogenic dose (35 mg/kg, s. c.) to fasted (24 h) and fed rats. Somatic pain sensitivity was evaluated using a tail flick test. Latency time was measured under conditions of the formation of gastric erosion (1 - 4 h after IM injection) as well as small intestinal injury (24, 48 and 72 h after IM injection). IM administration caused the gastric erosion formation only in fasted rats (4 h after the administration) and the small intestinal injury in both fasted and fed rats (24, 48, 72 h after the administration). Indomethacin-caused gastric and small intestinal injury resulted in an increase in tail flick latency. We did not observe any changes in tail flick latency in IM-treated rats without significant gastrointestinal injury. The gastrointestinal injury was accompanied by signs of chronic stress: long-lasting increase in corticosterone blood level, adrenal hypertrophy, thymus involution, and loss of body weight. Thus, the IM-induced gastrointestinal injury formation resulted in somatic pain inhibition in awake rats.

  8. Somatic pain sensitivity during formation and healing of acetic acid-induced gastric ulcers in conscious rats.

    PubMed

    Yarushkina, Natalya; Bogdanov, Anatoly; Filaretova, Ludmila

    2006-06-30

    A classical feature of visceral pain is its referring to somatic locations. Gastric ulcer is a source of visceral pain. In the present study we investigated whether gastric ulcers may trigger the changes in somatic nociception. For this aim somatic pain sensitivity was estimated under conditions of gastric ulcer development and healing. Gastric ulcers were induced by luminal application of 60% acetic acid under surgical conditions. Control rats were subjected to the same surgical procedure, but with the application of saline instead of the acid. Somatic pain sensitivity (tail flick latency), plasma corticosterone level, adrenal and thymus weight were investigated under conditions of the formation and the healing of gastric ulcers. The application of the acid resulted in the formation of kissing gastric ulcers, the increase of somatic pain sensitivity (the decrease of tail flick latency) as well as the appearance of typical signs of chronic stress: long-lasting increase of plasma corticosterone level, adrenal gland hypertrophy and thymus gland involution. Natural healing of gastric ulcers was accompanied by restoration of pain sensitivity as well as attenuation of the signs of chronic stress. Delay of ulcer healing by the daily indomethacin administration (2 mg/kg, s.c.) prevented the restoration of somatic pain sensitivity. The results suggest that chronic gastric ulcers may trigger somatic hypersensitivity.

  9. 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 ...

  10. Sensitivity to Change of Patient‐Preference Measures for Pain in Patients With Knee Osteoarthritis: Data From Two Trials

    PubMed Central

    Callaghan, Michael J.; O'Neill, Terence W.; Forsythe, Laura M.; Lunt, Mark; Felson, David T.

    2016-01-01

    Objective In osteoarthritis (OA) clinical trials, a pain measure that is most sensitive to change is considered optimal. We compared sensitivity to change of patient‐reported pain outcomes, including a patient‐preference measure (where the patient nominates an activity that aggravates their pain). Methods We used data from 2 trials of patients with confirmed (American College of Rheumatology criteria) knee OA: a trial of brace treatment for patellofemoral OA, and a trial of intraarticular steroids in knee OA. Both trials reported an improvement in pain following treatment. Participants rated pain on a 100‐mm visual analog scale (VAS), in the activity that caused them the most knee pain (VASNA), as well as completing questions on overall knee pain and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were also calculated from the KOOS. Standardized changes in each outcome were generated between treatment and control after 6 weeks intervention in the BRACE trial, and 1–2 weeks following intervention in the steroid trial. Results The VASNA produced standardized changes following treatment that were at least as large as other pain outcomes. In the BRACE trial, the between‐groups standardized change with the VASNA was −0.63, compared with the KOOS pain subscale change of −0.33, and pain in the last week VAS change of −0.56. In the steroid study, within‐group change following treatment in the VASNA was −0.60, compared to the last week VAS change of −0.51, and KOOS pain subscale change of −0.58. Conclusion Pain on nominated activity appears to be at least as, and in some cases more, sensitive to change than the KOOS/WOMAC questionnaire. PMID:26713415

  11. Anger regulation style, anger arousal and acute pain sensitivity: evidence for an endogenous opioid “triggering” model

    PubMed Central

    Burns, John W.; Bruehl, Stephen; Chont, Melissa

    2014-01-01

    Findings suggest that greater tendency to express anger is associated with greater sensitivity to acute pain via endogenous opioid system dysfunction, but past studies have not addressed the role of anger arousal. We used a 2 × 2 factorial design with Drug Condition (placebo or opioid blockade with naltrexone) crossed with Task Order (anger-induction/pain-induction or pain-induction/anger-induction), and with continuous Anger-out Subscale scores. Drug × Task Order × Anger-out Subscale interactions were tested for pain intensity during a 4-min ischemic pain task performed by 146 healthy people. A significant Drug × Task Order × Anger-out Subscale interaction was dissected to reveal different patterns of pain intensity changes during the pain task for high anger-out participants who underwent pain-induction prior to anger-induction compared to those high in anger-out in the opposite order. Namely, when angered prior to pain, high anger-out participants appeared to exhibit low pain intensity under placebo that was not shown by high anger-out participants who received naltrexone. Results hint that people with a pronounced tendency to express anger may suffer from inadequate opioid function under simple pain-induction, but may experience analgesic benefit to some extent from the opioid triggering properties of strong anger arousal. PMID:23624641

  12. Longitudinal development of pain sensitivity in adolescent non-suicidal self-injury.

    PubMed

    Koenig, Julian; Rinnewitz, Lena; Niederbäumer, Maren; Strozyk, Tabea; Parzer, Peter; Resch, Franz; Kaess, Michael

    2017-02-04

    Nonsuicidal self-injury (NSSI) is associated with reduced pain sensitivity (PS). Existing theories posit that altered PS is a risk factor for NSSI. Cross-sectional data suggest that PS normalizes in those terminating self-injury. However, previously no study addressed the longitudinal course of PS in patients engaging in NSSI. We addressed changes in PS and clinical symptomatology in adolescents with NSSI (n = 18) and matched controls (n = 19) over one year. Despite significant clinical improvements, PS did not change in the NSSI group but decreased in controls. Greater NSSI reduction was associated with increased pain tolerance. Findings are discussed in the light of current theories on PS in NSSI.

  13. Central sensitization and changes in conditioned pain modulation in people with chronic nonspecific low back pain: a case-control study.

    PubMed

    Corrêa, Juliana Barbosa; Costa, Leonardo Oliveira Pena; de Oliveira, Naiane Teixeira Bastos; Sluka, Kathleen A; Liebano, Richard Eloin

    2015-08-01

    Quantitative sensory testing is widely used in human research to investigate the state of the peripheral and central nervous system contributions in pain processing. It is a valuable tool to help identify central sensitization and may be important in the treatment of low back pain. The aim of this study was to evaluate changes in local and segmental hypersensitivity and endogenous pain inhibition in people with chronic nonspecific low back pain. Thirty patients with chronic low back pain and thirty healthy subjects were studied. Pressure pain thresholds (PPTs) were measured from the lumbar region and over the tibialis anterior muscle (TA). A cold pressor test was used to assess the activation of conditioned pain modulation (CPM), and PPTs in the lumbar region were recorded 30 s after immersion of participant's foot in a bucket with cold water. People with chronic low back pain have significantly lower PPT than controls at both the lumbar region [89.5 kPa (mean difference) 95 % CI 40.9-131.1 kPa] and TA [59.45 kPa (mean difference) 95 % CI 13.49-105.42 kPa]. During CPM, people with chronic low back pain have significantly lower PPT than controls in lumbar region [118.6 kPa (mean difference) 95 % CI 77.9-159.2 kPa]. Women had significantly lower PPTs than men in both lumbar region [101.7 kPa (mean difference) 95 % CI 37.9-165.7 kPa] and over the TA [189.7 kPa (mean difference) 95 % CI 14.2-145.2 kPa]. There was no significant difference in PPTs in men between healthy controls and those with low back pain, suggesting the significant differences are mediated primarily by difference between women.

  14. Central sensitization and changes in conditioned pain modulation in people with chronic nonspecific low back pain: a case–control study

    PubMed Central

    Corrêa, Juliana Barbosa; Costa, Leonardo Oliveira Pena; de Oliveira, Naiane Teixeira Bastos; Sluka, Kathleen A.

    2015-01-01

    Quantitative sensory testing is widely used in human research to investigate the state of the peripheral and central nervous system contributions in pain processing. It is a valuable tool to help identify central sensitization and may be important in the treatment of low back pain. The aim of this study was to evaluate changes in local and segmental hypersensitivity and endogenous pain inhibition in people with chronic nonspecific low back pain. Thirty patients with chronic low back pain and thirty healthy subjects were studied. Pressure pain thresholds (PPTs) were measured from the lumbar region and over the tibialis anterior muscle (TA). A cold pressor test was used to assess the activation of conditioned pain modulation (CPM), and PPTs in the lumbar region were recorded 30 s after immersion of participant’s foot in a bucket with cold water. People with chronic low back pain have significantly lower PPT than controls at both the lumbar region [89.5 kPa (mean difference) 95 % CI 40.9–131.1 kPa] and TA [59.45 kPa (mean difference) 95 % CI 13.49–105.42 kPa]. During CPM, people with chronic low back pain have significantly lower PPT than controls in lumbar region [118.6 kPa (mean difference) 95 % CI 77.9–159.2 kPa]. Women had significantly lower PPTs than men in both lumbar region [101.7 kPa (mean difference) 95 % CI 37.9–165.7 kPa] and over the TA [189.7 kPa (mean difference) 95 % CI 14.2–145.2 kPa]. There was no significant difference in PPTs in men between healthy controls and those with low back pain, suggesting the significant differences are mediated primarily by difference between women. PMID:25963754

  15. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint.

    PubMed

    Burston, James J; Sagar, Devi Rani; Shao, Pin; Bai, Mingfeng; King, Emma; Brailsford, Louis; Turner, Jenna M; Hathway, Gareth J; Bennett, Andrew J; Walsh, David A; Kendall, David A; Lichtman, Aron; Chapman, Victoria

    2013-01-01

    Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA

  16. 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

  17. Monitoring Sensitive Bat Species at Los Alamos National Laboratory

    SciTech Connect

    Schoenberg, Kari M.

    2014-01-15

    Bats play a critical role in ecosystems and are vulnerable to disturbance and disruption by human activities. In recent decades, bat populations in the United States and elsewhere have decreased tremendously. There are 47 different species of bat in the United States and 28 of these occur in New Mexico with 15 different species documented at the Los Alamos National Laboratory (LANL) and surrounding areas. Euderma maculatum(the spotted bat) is listed as “threatened” by the state of New Mexico and is known to occur at LANL. Four other species of bats are listed as “sensitive” and also occur here. In 1995, a four year study was initiated at LANL to assess the status of bat species of concern, elucidate distribution and relative abundance, and obtain information on roosting sites. There have been no definitive studies since then. Biologists in the Environmental Protection Division at LANL initiated a multi-year monitoring program for bats in May 2013 to implement the Biological Resources Management Plan. The objective of this ongoing study is to monitor bat species diversity and seasonal activity over time at LANL. Bat species diversity and seasonal activity were measured using an acoustic bat detector, the Pettersson D500X. This ultrasound recording unit is intended for long-term, unattended recording of bat and other high frequency animal calls. During 2013, the detector was deployed at two locations around LANL. Study sites were selected based on proximity to water where bats may be foraging. Recorded bat calls were analyzed using Sonobat, software that can help determine specific species of bat through their calls. A list of bat species at the two sites was developed and compared to lists from previous studies. Species diversity and seasonal activity, measured as the number of call sequences recorded each month, were compared between sites and among months. A total of 17,923 bat calls were recorded representing 15 species. Results indicate that there is a

  18. The lipid kinase PIP5K1C regulates pain signaling and sensitization

    PubMed Central

    Wright, Brittany D.; Loo, Lipin; Street, Sarah E.; Ma, Anqi; Taylor-Blake, Bonnie; Stashko, Michael A.; Jin, Jian; Janzen, William P.; Frye, Stephen V.; Zylka, Mark J.

    2014-01-01

    SUMMARY Numerous pain-producing (pronociceptive) receptors signal via phosphatidylinositol 4,5- bisphosphate (PIP2) hydrolysis. However, it is currently unknown which lipid kinases generate PIP2 in nociceptive dorsal root ganglia (DRG) neurons and if these kinases regulate pronociceptive receptor signaling. Here, we found that phosphatidylinositol 4-phosphate 5 kinase type 1C (PIP5K1C) is expressed at higher levels than any other PIP5K and, based on experiments with Pip5k1c+/− mice, generates at least half of all PIP2 in DRG neurons. Additionally, Pip5k1c haploinsufficiency reduces pronociceptive receptor signaling and TRPV1 sensitization in DRG neurons as well as thermal and mechanical hypersensitivity in mouse models of chronic pain. We identified a novel small molecule inhibitor of PIP5K1C (UNC3230) in a high-throughput screen. UNC3230 lowered PIP2 levels in DRG neurons and attenuated hypersensitivity when administered intrathecally or into the hindpaw. Our studies reveal that PIP5K1C regulates PIP2- dependent nociceptive signaling and suggest that PIP5K1C is a novel therapeutic target for chronic pain. PMID:24853942

  19. Is pressure pain sensitivity over the cervical musculature associated with neck disability in individuals with migraine?

    PubMed

    Gonçalves, Maria Claudia; Chaves, Thaís Cristina; Florencio, Lidiane Lima; Carvalho, Gabriela Ferreira; Dach, Fabíola; Fernández-De-Las-Penãs, Cesar; Bevilaqua-Grossi, Débora

    2015-01-01

    The objective was to determine if disability due to neck pain is correlated with pressure pain sensitivity in the cervical muscles in patients with migraine. Thirty-two volunteers with migraine completed the Neck Disability Index (NDI). Pressure pain thresholds (PPT) over the sternocleidomastoid, upper trapezius and suboccipital muscles were also assessed. Data were analyzed using the Spearman correlation coefficient (rs) and linear regression models (α < 0.05). Moderate negative correlations between NDI and PPT were obtained for the sternocleidomastoid (rs = -0.42; p = 0.001), upper trapezius (rs = -0.33; p = 0.001) and suboccipital muscles (rs = -0.41; p = 0.001). The linear regression revealed no association between NDI and PPT of sternocleidomastoid (β = 0.01; R(2) = 0.17), upper trapezius (β = 0.01; R(2) = 0.11) and suboccipital muscles (β = 0.02; R(2) = 0.17). NDI scores and PPT of the cervical muscles correlated moderately and was inversely proportional in patients with migraine, but the association was not linear, so both outcomes should be considered in the assessment of this population.

  20. Psychophysical demonstration of bidirectional pain modulation (sensitization and desensitization) by ascending or descending progressions of thermal stimulus intensity.

    PubMed

    Vierck, Charles J; Riley, Joseph L; Wong, Fong; King, Christopher D; Mauderli, Andre P

    2010-08-06

    A psychophysical method of response-dependent stimulation presented ascending and descending series of thermal stimulus intensities that maintained an average rating (setpoint) of mild pain (20 on a scale of 0-100) or moderate pain (35). Subjects were presented with alternating series of thermal stimuli that increased until ratings reached or exceeded the setpoint, then decreased until ratings equaled or were less than the setpoint, then increased, etc. Plots of pain intensity ratings differed substantially for series of ascending and descending stimulus intensities. After an ascending series, pain ratings during a descending series were higher than predicted, and after a descending series, pain ratings during an ascending series were lower than predicted. Thus, the nervous system detects and discriminates between ascending and descending trends in stimulus intensity and alters the magnitude of pain sensations in the direction of the trend of increasing or decreasing stimulus intensity. Ascending (sensitizing) trend effects may increase the magnitude of pathological pain in the absence of treatment, and descending (desensitizing) trend effects likely would enhance the efficacy of procedures that reduce pain sensitivity.

  1. 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

  2. NR2B receptor blockade inhibits pain-related sensitization of amygdala neurons.

    PubMed

    Ji, Guangchen; Horváth, Csilla; Neugebauer, Volker

    2009-04-28

    Pain-related sensitization and synaptic plasticity in the central nucleus of the amygdala (CeA) depend on the endogenous activation of NMDA receptors and phosphorylation of the NR1 subunit through a PKA-dependent mechanism. Functional NMDA receptors are heteromeric assemblies of NR1 with NR2A-D or NR3A, B subunits. NMDA receptors composed of NR1 and NR2B subunits have been implicated in neuroplasticity and are present in the CeA. Here we used a selective NR2B antagonist (Ro-256981) to determine the contribution of NR2B-containing NMDA receptors to pain-related sensitization of CeA neurons. Extracellular single-unit recordings were made from CeA neurons in anesthetized adult male rats before and during the development of an acute arthritis. Arthritis was induced in one knee joint by intraarticular injections of kaolin and carrageenan. Brief (15 s) mechanical stimuli of innocuous (100-500 g/30 mm2) and noxious (1000-2000 g/30 mm2) intensity were applied to the knee and other parts of the body. In agreement with our previous studies, all CeA neurons developed increased background and evoked activity after arthritis induction. Ro-256981 (1, 10 and 100 muM; 15 min each) was administered into the CeA by microdialysis 5-6 h postinduction of arthritis. Ro-256981 concentration-dependently decreased evoked responses, but not background activity. This pattern of effect is different from that of an NMDA receptor antagonist (AP5) in our previous studies. AP5 (100 microM - 5 mM) inhibited background activity and evoked responses. The differential effects of AP5 and Ro-256981 may suggest that NMDA receptors containing the NR2B subunit are important but not sole contributors to pain-related changes of CeA neurons.

  3. Inducing Expectations for Health: Effects of Verbal Suggestion and Imagery on Pain, Itch, and Fatigue as Indicators of Physical Sensitivity

    PubMed Central

    Peerdeman, Kaya J.; van Laarhoven, Antoinette I. M.; Donders, A. Rogier T.; Hopman, Maria T. E.; Peters, Madelon L.; Evers, Andrea W. M.

    2015-01-01

    Research into placebo effects has convincingly shown that inducing positive outcome expectations can reduce pain and other physical sensations. However, the comparative effects of different expectation inductions, such as verbal suggestion or mental imagery, and their generic effects on physical sensitivity, to different sensations such as pain, itch, and fatigue, are still largely unknown. In the current study, we assessed the individual and combined effects of verbal suggestion and imagery on pain, itch, and fatigue as indicators of physical sensitivity in a randomized study design. Healthy participants (n = 116) were given an inert (placebo) capsule that was said to be effective for reducing physical sensitivity in either the majority (positive verbal suggestion) or the minority (control verbal suggestion) of users. Subsequently, they imagined either their best possible health (positive imagery) or a typical day (control imagery). Sensitivity to pain, itch, and fatigue was tested using a cold pressor test, histamine iontophoresis, and a bicycle test, respectively. Heart rate and skin conductance were recorded continuously. Results showed that positive verbal suggestion and imagery successfully induced positive expectations, but they did not affect physical sensitivity, as indicated by sensitivity to pain, itch, or fatigue, or concurrent physiological responses. These results could indicate that the specificity and concreteness of expectation inductions might be important for their applicability in the treatment of physical symptoms. Trial Registration Nederlands Trial Register NTR3641 PMID:26448183

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

    PubMed

    Theodorou, Vassilia; Ait Belgnaoui, Afifa; 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.

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

    PubMed Central

    2013-01-01

    Background 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. Methods 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). Results 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. Conclusions 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

  6. Sensitization of neonatal rat lumbar motoneuron by the inflammatory pain mediator bradykinin

    PubMed Central

    Bouhadfane, Mouloud; Kaszás, Attila; Rózsa, Balázs; Harris-Warrick, Ronald M; Vinay, Laurent; Brocard, Frédéric

    2015-01-01

    Bradykinin (Bk) is a potent inflammatory mediator that causes hyperalgesia. The action of Bk on the sensory system is well documented but its effects on motoneurons, the final pathway of the motor system, are unknown. By a combination of patch-clamp recordings and two-photon calcium imaging, we found that Bk strongly sensitizes spinal motoneurons. Sensitization was characterized by an increased ability to generate self-sustained spiking in response to excitatory inputs. Our pharmacological study described a dual ionic mechanism to sensitize motoneurons, including inhibition of a barium-sensitive resting K+ conductance and activation of a nonselective cationic conductance primarily mediated by Na+. Examination of the upstream signaling pathways provided evidence for postsynaptic activation of B2 receptors, G protein activation of phospholipase C, InsP3 synthesis, and calmodulin activation. This study questions the influence of motoneurons in the assessment of hyperalgesia since the withdrawal motor reflex is commonly used as a surrogate pain model. DOI: http://dx.doi.org/10.7554/eLife.06195.001 PMID:25781633

  7. Clinical Evaluation Versus Undetectable High-Sensitivity Troponin for Assessment of Patients With Acute Chest Pain.

    PubMed

    Sanchis, Juan; García-Blas, Sergio; Carratalá, Arturo; Valero, Ernesto; Mollar, Anna; Miñana, Gema; Ruiz, Vicente; Balaguer, Jose Vicente; Roqué, Mercé; Bosch, Xavier; Núñez, Julio

    2016-12-01

    Decision-making in acute chest pain remains challenging despite normal (below ninety-ninth percentile) high-sensitivity troponin (hs-cTn). Some studies suggest that undetectable hs-cTn, far below the ninety-ninth percentile, might rule out acute coronary syndrome. We investigated clinical data in comparison to undetectable hs-cTnT. The study comprised 682 patients (November 2010 to September 2011) presenting at the emergency department with chest pain and normal hs-cTnT (<14 ng/l). The main end point was major adverse cardiac events (MACE: death, myocardial infarction, readmission for unstable angina, or revascularization) at a 4-year median follow-up; secondary end point was 30-day MACE. A clinical score was built by assigning points according to hazard ratios of the independent predictive variables: 1 point (male and effort-related pain) and 2 points (recurrent pain and prior ischemic heart disease). The negative predictive values of the clinical score and undetectable hs-cTnT (<5 ng/l), were tested. A total of 72 (10.6%) patients suffered long-term MACE. The C-statistics of the clinical score for long-term (0.75) and 30-day (0.88) MACE were higher than with the TIMI(Thrombolysis In Myocardial Infarction) risk (0.68, 0.77) or GRACE(Global Registry of Acute Coronary Events) (0.50, 0.47) scores. Likewise, the negative predictive values of score = 0 (97.5%, 100%) and ≤1 point (95.9%, 100%) were higher than using undetectable hs-cTnT (91.9%, 98.1%). Both clinical scores of 0 and ≤1 better classified patients at risk of MACE (p = 0.0001, log-rank test) than hs-cTnT <5 ng/l (p = 0.06). In conclusion, clinical data can guide decision-making and perform at least equally well as undetectable hs-cTnT, in patients presenting at the emergency department with chest pain and normal hs-cTnT.

  8. 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.

  9. Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans.

    PubMed

    Henrich, Florian; Magerl, Walter; Klein, Thomas; Greffrath, Wolfgang; Treede, Rolf-Detlef

    2015-09-01

    Long-term potentiation in the spinal dorsal horn requires peptidergic C-fibre activation in animals. Perceptual correlates of long-term potentiation following high-frequency electrical stimulation in humans include increased sensitivity to electrical stimuli at the high frequency stimulation site (homotopic pain-long-term potentiation) and increased sensitivity to pinprick surrounding the high frequency stimulation site (heterotopic pain-long-term potentiation, equivalent to secondary hyperalgaesia). To characterize the peripheral fibre populations involved in induction of pain-long-term potentiation, we performed two selective nerve block experiments in 30 healthy male volunteers. Functional blockade of TRPV1-positive nociceptors by high-concentration capsaicin (verified by loss of heat pain) significantly reduced pain ratings to high frequency stimulation by 47% (P < 0.001), homotopic pain-long-term potentiation by 71% (P < 0.01), heterotopic pain-long-term potentiation by 92% (P < 0.001) and the area of secondary hyperalgesia by 76% (P < 0.001). The selective blockade of A-fibre conduction by nerve compression (verified by loss of first pain to pinprick) significantly reduced pain ratings to high frequency stimulation by 37% (P < 0.01), but not homotopic pain-long-term potentiation (-5%). It had a marginal effect on heterotopic pain-long-term potentiation (-35%, P = 0.059), while the area of secondary hyperalgesia remained unchanged (-2%, P = 0.88). In conclusion, all nociceptor subclasses contribute to high frequency stimulation-induced pain (with a relative contribution of C > Aδ fibres, and an equal contribution of TRPV1-positive and TRPV1-negative fibres). TRPV1-positive C-fibres are the main inducers of both homotopic and heterotopic pain-long-term potentiation. TRPV1-positive A-fibres contribute substantially to the induction of heterotopic pain-long-term potentiation. TRPV1-negative C-fibres induce a component of homotopic self-facilitation but not

  10. The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

    PubMed

    Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

    2016-02-01

    A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes.

  11. 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.

  12. Was it a pain or a sound? Across-species variability in sensory sensitivity.

    PubMed

    Hu, Li; Xia, Xiaolei L; Peng, Weiwei W; Su, Wenxin X; Luo, Fei; Yuan, Hong; Chen, Antao T; Liang, Meng; Iannetti, Giandomenico

    2015-12-01

    Natural selection has shaped the physiological properties of sensory systems across species, yielding large variations in their sensitivity. Here, we used laser stimulation of skin nociceptors, a widely used technique to investigate pain in rats and humans, to provide a vivid example of how ignoring these variations can lead to serious misconceptions in sensory neuroscience. In 6 experiments, we characterized and compared the physiological properties of the electrocortical responses elicited by laser stimulation in rats and humans. We recorded the electroencephalogram from the surface of the brain in freely moving rats and from the scalp in healthy humans. Laser stimuli elicited 2 temporally distinct responses, traditionally interpreted as reflecting the concomitant activation of different populations of nociceptors with different conduction velocities: small-myelinated Aδ-fibres and unmyelinated C-fibres. Our results show that this interpretation is valid in humans, but not in rats. Indeed, the early response recorded in rats does not reflect the activation of the somatosensory system, but of the auditory system by laser-generated ultrasounds. These results have wide implications: retrospectively, as they prompt for a reconsideration of a large number of previous interpretations of electrocortical rat recordings in basic, preclinical, and pharmacological research, and prospectively, as they will allow recording truly pain-related cortical responses in rats.

  13. Was it a pain or a sound? Across-species variability in sensory sensitivity

    PubMed Central

    Hu, Li; Xia, Xiaolei L.; Peng, Weiwei W.; Su, Wenxin X.; Luo, Fei; Yuan, Hong; Chen, Antao T.; Liang, Meng; Iannetti, Giandomenico

    2015-01-01

    Abstract Natural selection has shaped the physiological properties of sensory systems across species, yielding large variations in their sensitivity. Here, we used laser stimulation of skin nociceptors, a widely used technique to investigate pain in rats and humans, to provide a vivid example of how ignoring these variations can lead to serious misconceptions in sensory neuroscience. In 6 experiments, we characterized and compared the physiological properties of the electrocortical responses elicited by laser stimulation in rats and humans. We recorded the electroencephalogram from the surface of the brain in freely moving rats and from the scalp in healthy humans. Laser stimuli elicited 2 temporally distinct responses, traditionally interpreted as reflecting the concomitant activation of different populations of nociceptors with different conduction velocities: small-myelinated Aδ-fibres and unmyelinated C-fibres. Our results show that this interpretation is valid in humans, but not in rats. Indeed, the early response recorded in rats does not reflect the activation of the somatosensory system, but of the auditory system by laser-generated ultrasounds. These results have wide implications: retrospectively, as they prompt for a reconsideration of a large number of previous interpretations of electrocortical rat recordings in basic, preclinical, and pharmacological research, and prospectively, as they will allow recording truly pain-related cortical responses in rats. PMID:26270592

  14. HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model

    PubMed Central

    Matsushita, Yosuke; Araki, Kohei; Omotuyi, Olaposi idowu; Mukae, Takehiro; Ueda, Hiroshi

    2013-01-01

    Background and Purpose Hypoesthesia is a clinical feature of neuropathic pain. The feature is partly explained by the evidence of epigenetic repression of Nav1.8 sodium channel in the dorsal root ganglion (DRG). Experimental Approach We investigated the possibility of trichostatin A (TSA), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to reverse the unique C-fibre sensitivity observed following partial ligation of sciatic nerve in mice. Key Results Nerve injury-induced down-regulation of DRG Nav1.8 sodium channel and C-fibre-related hypoesthesia were reversed by TSA, VPA and SAHA treatments, which inhibit histone deacetylase (HDAC), and increase histone acetylation at the regulatory sequence of Nav1.8. Conclusions and Implications Taken together, these studies provide the evidence that hypoesthesia and underlying down-regulation of Nav1.8, negative symptoms observed in nerve injury-induced neuropathic pain models are regulated by an epigenetic chromatin remodelling through HDAC-related machineries. PMID:24032674

  15. Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans.

    PubMed

    Ceko, Marta; Milenkovic, Nevena; le Coutre, Philipp; Westermann, Jörg; Lewin, Gary R

    2014-07-01

    The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, whereas activation of c-Kit produces hypersensitivity to noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study, we investigated the role of c-Kit signaling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRα, and PDFGFRβ, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male and 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile thresholds were unchanged compared to those in the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to those of several common analgesics; thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans.

  16. Determination of Mass Sensitivity of Crystal Quartz Resonators at Students' Laboratory

    ERIC Educational Resources Information Center

    Greczylo, Tomasz; Mazur, Piotr; Debowska, Ewa; Wieczorek, Piotr

    2010-01-01

    This paper presents an experiment in which students determine the mass sensitivity of three crystal quartz resonators, designed to be carried out in "Physics Laboratory II" at the Institute of Experimental Physics, University of Wroclaw. The authors discuss the process of setting up the experiment and the results of the measurements.…

  17. Increased muscular and cutaneous pain sensitivity in cephalic region in patients with chronic tension-type headache.

    PubMed

    Ashina, S; Babenko, L; Jensen, R; Ashina, M; Magerl, W; Bendtsen, L

    2005-07-01

    Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial nociception may be responsible for transformation of episodic tension-type headache into chronic form. We aimed to compare mechanical and electrical (intramuscular and cutaneous) pain thresholds in trapezius and anterior tibial regions between 20 patients with chronic tension type headache and 20 healthy controls. Pain thresholds to three types of electrical stimulation (single pulse, 2 and 100 Hz) were significantly lower in patients than in controls in trapezius muscle (P < 0.02) and in skin overlying the trapezius muscle (P < 0.05), whilst electrical pain thresholds did not differ between groups in anterior tibial muscle and skin. Quantitative sensory testing revealed increased pain sensitivity in patients as assessed by pressure-controlled manual palpation (local tenderness score, LTS; P < 0.01) and by pressure algometry (mechanical pain thresholds; P < 0.05) in test areas over the trapezius muscle, but not the anterior tibial muscle. In summary, this study demonstrates lower pain thresholds in muscle and skin of the cephalic region but not in lower limb muscle and skin in patients with chronic tension-type headache than in healthy controls. Increased sensitivity in nociceptive pathways from cephalic region may be of importance in the pathophysiology of chronic tension type headache.

  18. 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

  19. A basic Michelson laser interferometer for the undergraduate teaching laboratory demonstrating picometer sensitivity

    NASA Astrophysics Data System (ADS)

    Libbrecht, Kenneth G.; Black, Eric D.

    2015-05-01

    We describe a basic Michelson laser interferometer experiment for the undergraduate teaching laboratory that achieves picometer sensitivity in a hands-on, table-top instrument. In addition to providing an introduction to interferometer physics and optical hardware, the experiment also focuses on precision measurement techniques including servo control, signal modulation, phase-sensitive detection, and different types of signal averaging. Students examine these techniques in a series of steps that take them from micron-scale sensitivity using direct fringe counting to picometer sensitivity using a modulated signal and phase-sensitive signal averaging. After students assemble, align, and characterize the interferometer, they then use it to measure nanoscale motions of a simple harmonic oscillator system as a substantive example of how laser interferometry can be used as an effective tool in experimental science.

  20. The effects of manual therapy and exercise directed at the cervical spine on pain and pressure pain sensitivity in patients with myofascial temporomandibular disorders.

    PubMed

    La Touche, R; Fernández-de-las-Peñas, C; Fernández-Carnero, J; Escalante, K; Angulo-Díaz-Parreño, S; Paris-Alemany, A; Cleland, J A

    2009-09-01

    No studies have investigated the effects of the treatments directed at the cervical spine in patients with temporomandibular disorders (TMD). Our aim was to investigate the effects of joint mobilization and exercise directed at the cervical spine on pain intensity and pressure pain sensitivity in the muscles of mastication in patients with TMD. Nineteen patients (14 females), aged 19-57 years, with myofascial TMD were included. All patients received a total of 10 treatment session over a 5-week period (twice per week). Treatment included manual therapy techniques and exercise directed at the cervical spine. Outcome measures included bilateral pressure pain threshold (PPT) levels over the masseter and temporalis muscles, active pain-free mouth opening (mm) and pain (Visual Analogue Scale) and were all assessed pre-intervention, 48 h after the last treatment (post-intervention) and at 12-week follow-up period. Mixed-model anovas were used to examine the effects of the intervention on each outcome measure. Within-group effect sizes were calculated in order to assess clinical effect. The 2 x 3 mixed model anova revealed significant effect for time (F = 77.8; P < 0.001) but not for side (F = 0.2; P = 0.7) for changes in PPT over the masseter muscle and over the temporalis muscle (time: F = 66.8; P < 0.001; side: F = 0.07; P = 0.8). Post hoc revealed significant differences between pre-intervention and both post-intervention and follow-up periods (P < 0.001) but not between post-intervention and follow-up period (P = 0.9) for both muscles. Within-group effect sizes were large (d > 1.0) for both follow-up periods in both muscles. The anova found a significant effect for time (F = 78.6; P < 0.001) for changes in pain intensity and active pain-free mouth opening (F = 17.1; P < 0.001). Significant differences were found between pre-intervention and both post-intervention and follow-up periods (P < 0.001) but not between the post-intervention and follow-up period (P > 0

  1. Overexpressed TRPV3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2

    PubMed Central

    Huang, Susan M.; Lee, Hyosang; Chung, Man-Kyo; Park, Una; Yu, Yin Yin; Bradshaw, Heather B.; Coulombe, Pierre A.; Walker, J. Michael; Caterina, Michael J.

    2009-01-01

    The ability to sense changes in the environment is essential for survival because it permits responses such as withdrawal from noxious stimuli and regulation of body temperature. Keratinocytes, which occupy much of the skin epidermis, are situated at the interface between the external environment and the body's internal milieu, and have long been appreciated for their barrier function against external insults. The recent discovery of temperature-sensitive TRPV ion channels in keratinocytes has raised the possibility that these cells also actively participate in acute temperature and pain sensation. To address this notion, we generated and characterized transgenic mice that overexpress TRPV3 in epidermal keratinocytes under the control of the keratin 14 promoter. Compared to wild-type controls, keratinocytes overexpressing TRPV3 exhibited larger currents as well as augmented prostaglandin E2 (PGE2) release in response to two TRPV3 agonists, 2-aminoethoxydiphenyl borate (2APB) and heat. Thermal selection behavior and heat-evoked withdrawal behavior of naïve mice overexpressing TRPV3 were not consistently altered. Upon selective pharmacological inhibition of TRPV1 with JNJ-7203212, however, the keratinocyte-specific TRPV3 transgenic mice showed increased escape responses to noxious heat relative to their wild-type littermates. Co-administration of the cyclooxygenase inhibitor, ibuprofen, with the TRPV1 antagonist decreased inflammatory thermal hyperalgesia in transgenic but not wild-type animals. Our results reveal a previously undescribed mechanism for keratinocyte participation in thermal pain transduction through keratinocyte TRPV3 ion channels and the intercellular messenger PGE2. PMID:19091963

  2. Long-Term Effects of Neonatal Morphine Infusion on Pain Sensitivity: Follow-Up of a Randomized Controlled Trial.

    PubMed

    Valkenburg, Abraham J; van den Bosch, Gerbrich E; de Graaf, Joke; van Lingen, Richard A; Weisglas-Kuperus, Nynke; van Rosmalen, Joost; Groot Jebbink, Liesbeth J M; Tibboel, Dick; van Dijk, Monique

    2015-09-01

    Short-term and long-term effects of neonatal pain and its analgesic treatment have been topics of translational research over the years. This study aimed to identify the long-term effects of continuous morphine infusion in the neonatal period on thermal pain sensitivity, the incidence of chronic pain, and neurological functioning. Eighty-nine of the 150 participants of a neonatal randomized controlled trial on continuous morphine infusion versus placebo during mechanical ventilation underwent quantitative sensory testing and neurological examination at the age of 8 or 9 years. Forty-three children from the morphine group and 46 children from the placebo group participated in this follow-up study. Thermal detection and pain thresholds were compared with data from 28 healthy controls. Multivariate analyses revealed no statistically significant differences in thermal detection thresholds and pain thresholds between the morphine and placebo groups. The incidence of chronic pain was comparable between both groups. The neurological examination was normal in 29 (76%) of the children in the morphine group and 25 (61%) of the children in the control group (P = .14). We found that neonatal continuous morphine infusion (10 μg/kg/h) has no adverse effects on thermal detection and pain thresholds, the incidence of chronic pain, or overall neurological functioning 8 to 9 years later. Perspective: This unique long-term follow-up study shows that neonatal continuous morphine infusion (10 μg/kg/h) has no long-term adverse effects on thermal detection and pain thresholds or overall neurological functioning. These findings will help clinicians to find the most adequate and safe analgesic dosing regimens for neonates and infants.

  3. Pain and placebo in pediatrics: A comprehensive review of laboratory and clinical findings

    PubMed Central

    Kossowsky, Joe; Krummenacher, Peter; Grillon, Christian; Pine, Daniel; Colloca, Luana

    2014-01-01

    Pain modulation by placebo mechanisms is one of the most robust and best-studied phenomena, yet almost all research investigating the mechanisms and implications of the placebo analgesia are based on adult research. After highlighting crucial aspects that need to be considered in studying pain modulation in children, this comprehensive review examines studies related to pain modulation with an emphasis on factors such as age, neural development and pain measures. Psychological mechanisms underlying placebo effects including: 1) verbally-induced expectations; 2) conditioning and learning mechanisms; 3) child-parent-physician interactions are critically discussed. Taken together, research suggests that placebo mechanisms can impact therapeutic outcomes and potentially be exploited clinically to improve clinical outcomes in pediatric population. Recommendations for further investigating the mechanistic bases and harnessing placebo effects for supportive therapeutic applications are given. PMID:25180010

  4. The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain.

    PubMed

    Rode, Frederik; Thomsen, Mads; Broløs, Tine; Jensen, Dorthe G; Blackburn-Munro, Gordon; Bjerrum, Ole J

    2007-06-14

    Neuropathic pain conditions can encompass a diverse constellation of signs and symptoms consisting of sensory deficits, allodynia and hyperalgesia. Animal models of neuropathic pain have enabled the identification of key pathophysiological changes occurring within nociceptive pathways as a result of injury, and serve an invaluable role for preclinical screening of novel analgesic candidates. We have produced the first systematic description of the development and maintenance, and the pharmacological sensitivity of nociceptive behaviours in four rat strains with different genetic background (outbred Sprague-Dawley and inbred Brown Norway, Lewis and Fischer 344 rats), using the spared nerve injury model of peripheral neuropathic pain. Hindpaw mechanical hypersensitivity was evident from 7 to 30 days post-injury in all four strains, developing most quickly and severely in Fischer 344 rats; Lewis rats were least affected. Morphine (6 but not 3 mg/kg, s.c.) and gabapentin (100 but not 50 mg/kg, s.c.) had significant antiallodynic and antihyperalgesic actions in all four strains after spared nerve injury, although marked differences in potency across strains were observed. Two strains (Fischer 344 rats and Lewis) were insensitive to the antihyperalgesic properties of gaboxadol (15 mg/kg) whereas gaboxadol (6 mg/kg) was equipotent to morphine (6 mg/kg) in two other strains (Sprague-Dawley and Brown Norway). The observed pharmacogenetic variations have important implications for the preclinical testing of drugs, and provide a basis for development of pharmacogenomics in neuropathic pain.

  5. Evidence of Heterosynaptic LTD in the Human Nociceptive System: Superficial Skin Neuromodulation Using a Matrix Electrode Reduces Deep Pain Sensitivity

    PubMed Central

    Mücke, Martin; Cuhls, Henning; Radbruch, Lukas; Weigl, Tobias; Rolke, Roman

    2014-01-01

    Long term depression (LTD) is a neuronal learning mechanism after low frequency stimulation (LFS). This study compares two types of electrodes (concentric vs. matrix) and stimulation frequencies (4 and 30 Hz) to examine homo- and heterosynaptic effects indirectly depicted from the somatosensory profile of healthy subjects. Both electrodes were compared in a prospective, randomized, controlled cross-over study using 4 Hz as the conditioning LFS compared to 30 Hz (intended sham condition). Quantitative sensory testing (QST) was used to examine 13 thermal and mechanical detection and pain thresholds. Sixteen healthy volunteers (10 women, age 31.0±12.7 years) were examined. Depending on the electrodes and frequencies used a divergent pattern of sensory minus signs occurred. Using LFS the concentric electrode increased thermal thresholds, while the matrix electrode rather increased mechanical including deep pain thresholds. Findings after cutaneous neuromodulation using LFS and a matrix electrode are consistent with the concept of heterosynaptic LTD in the human nociceptive system, where deep pain sensitivity was reduced after superficial stimulation of intraepidermal nerve fibres. Cutaneous neuromodulation using LFS and a matrix electrode may be a useful tool to influence deep pain sensitivity in a variety of chronic pain syndromes. PMID:25229556

  6. Heightened pain sensitivity in individuals with signs and symptoms of carpal tunnel syndrome and the relationship to clinical outcomes following a manual therapy intervention.

    PubMed

    Bialosky, Joel E; Bishop, Mark D; Robinson, Michael E; Price, Donald D; George, Steven Z

    2011-12-01

    Neurophysiological responses related to lessening of pain sensitivity are a suggested mechanism of manual therapy. Prior studies have observed generalized lower pain thresholds associated with carpal tunnel syndrome (CTS) in comparison to healthy controls. The present study sought to determine whether similar findings were present in suprathreshold measures and measures specific to central integration of pain (temporal summation and after sensations). Additionally, we wished to determine whether measures of pain sensitivity were related to clinical outcomes in participants with signs and symptoms of CTS receiving a manual therapy intervention. Individuals with signs and symptoms of CTS reported greater pain sensitivity to suprathreshold measures of mechanical pain, temporal summation, and after sensation in comparison to healthy controls. Immediate lessening of mechanical pain sensitivity and after sensations in response to a manual therapy intervention and 3-week attenuation of temporal summation following a 3-week course of manual therapy were associated with 3-week changes in clinical pain intensity in participants with signs and symptoms of CTS. These findings suggest heightened pain sensitivity across several parameters may be associated with CTS. Furthermore, changes in mechanical pain, after sensation, and temporal summation may be related to improvements in clinical outcomes.

  7. Role of ATP-sensitive potassium channels in modulating nociception in rat model of bone cancer pain.

    PubMed

    Xia, Hui; Zhang, Dengwen; Yang, Shijie; Wang, Yu; Xu, Lin; Wu, Jinjing; Ren, Jing; Yao, Wenlong; Fan, Longchang; Zhang, Chuanhan; Tian, Yuke; Pan, Hui-Lin; Wang, Xueren

    2014-03-20

    Bone cancer pain is a major clinical problem and remains difficult to treat. ATP-sensitive potassium (KATP) channels may be involved in regulating nociceptive transmission at the spinal cord level. We determined the role of spinal KATP channels in the control of mechanical hypersensitivity in a rat model of bone cancer pain. The rat model of bone cancer pain was induced by implanting rat mammary gland carcinoma cells (Walker256) into the tibias. KATP modulators (pinacidil and glibenclamide) or the specific Kir6.2-siRNA were injected via an intrathecal catheter. The mechanical withdrawal threshold of rats was tested using von Frey filaments. The Kir6.2 mRNA and protein levels were measured by quantitative PCR and western blots, respectively. Intrathecal injection of pinacidil, a KATP channel opener, significantly increased the tactile withdrawal threshold of cancer cell-injected rats in a dose-dependent manner. In contrast, intrathecal delivery of glibenclamide, a KATP channel blocker, or the specific Kir6.2-siRNA significantly reduced the tactile withdrawal threshold of cancer cell-injected rats. The mRNA and protein levels of Kir6.2 in the spinal cord of cancer cell-injected rats were significantly lower than those in control rats. Our findings suggest that the KATP channel expression level in the spinal cord is reduced in bone cancer pain. Activation of KATP channels at the spinal level reduces pain hypersensitivity associated with bone cancer pain.

  8. Palmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivity.

    PubMed

    Ghafouri, Nazdar; Ghafouri, Bijar; Larsson, Britt; Stensson, Niclas; Fowler, Christopher J; Gerdle, Björn

    2013-09-01

    Chronic widespread pain (CWP) is a complex condition characterized by central hyperexcitability and altered descending control of nociception. However, nociceptive input from deep tissues is suggested to be an important drive. N-Acylethanolamines (NAEs) are endogenous lipid mediators involved in regulation of inflammation and pain. Previously we have reported elevated levels of the 2 NAEs, the peroxisome proliferator-activated receptor type-α ligand N-palmitoylethanolamine (PEA) and N-stearoylethanolamine (SEA) in chronic neck/shoulder pain (CNSP). In the present study, the levels of PEA and SEA in women with CWP (n=18), CNSP (n=34) and healthy controls (CON, n=24) were investigated. All subjects went through clinical examination, pressure pain threshold measurements and induction of experimental pain in the tibialis anterior muscle. Microdialysis dialysate of the trapezius was collected before and after subjects performed a repetitive low-force exercise and analyzed by mass spectrometry. The levels of PEA and SEA in CNSP were significantly higher post exercise compared with CWP, and both pre and post exercise compared with CON. Levels of both NAEs decreased significantly pre to post exercise in CWP. Intercorrelations existed between aspects of pain intensity and sensitivity and the level of the 2 NAEs in CWP and CNSP. This is the first study demonstrating that CNSP and CWP differ in levels of NAEs in response to a low-force exercise which induces pain. Increases in pain intensity as a consequence of low-force exercise were associated with low levels of PEA and SEA in CNSP and CWP. These results indicate that PEA and SEA have antinociceptive roles in humans.

  9. Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: an ACTTION study.

    PubMed

    Farrar, John T; Troxel, Andrea B; Haynes, Kevin; Gilron, Ian; Kerns, Robert D; Katz, Nathaniel P; Rappaport, Bob A; Rowbotham, Michael C; Tierney, Ann M; Turk, Dennis C; Dworkin, Robert H

    2014-08-01

    The degree of variability in the patient baseline 7-day diary of pain ratings has been hypothesized to have a potential effect on the assay sensitivity of randomized clinical trials of pain therapies. To address this issue, we obtained clinical trial data from the Food and Drug Administration (FDA) through the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership, and harmonized patient level data from 12 clinical trials (4 gabapentin and 8 pregabalin) in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Models were developed using exploratory logistic regression to examine the interaction between available baseline factors and treatment (placebo vs active medication) in predicting patient response to therapy (ie, >30% improvement). Our analysis demonstrated an increased likelihood of response in the placebo-treated group for patients with a higher standard deviation in the baseline 7-day diary without affecting the likelihood of a response in the active medication-treated group, confirming our hypothesis. In addition, there was a small but significant age-by-treatment interaction in the PHN model, and small weight-by-treatment interaction in the DPN model. The patient's sex, baseline pain level, and the study protocol had an effect only on the likelihood of response overall. Our results suggest the possibility that, at least in some disease processes, excluding patients with a highly variable baseline 7-day diary has the potential to improve the assay sensitivity of these analgesic clinical trials, although reductions of external validity must be considered when increasing the homogeneity of the investigated sample.

  10. Inadequate Sensitivity of Laboratory Risk Indicator to Rule Out Necrotizing Fasciitis in the Emergency Department

    PubMed Central

    Burner, Elizabeth; Henderson, Sean O.; Burke, Guenevere; Nakashioya, Jeffrey; Hoffman, Jerome R.

    2016-01-01

    Introduction Necrotizing fasciitis (NF) is a life-threatening illness, particularly when surgical debridement is delayed. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was developed to identify patients at higher risk for NF. Despite limited information in this regard, the LRINEC score is often used to “rule out” NF if negative. We describe the sensitivity of the LRINEC score in emergency department (ED) patients for the diagnosis of NF. Methods We conducted a chart review of ED patients in whom coding of hospital discharge diagnoses included NF. We employed standard methods to minimize bias. We used laboratory data to calculate the LRINEC score, and confirmed the diagnosis of NF via explicit chart review. We then calculated the sensitivity of a positive LRINEC score (standardly defined as six or greater) in our cohort. We examined the role of patient characteristics in the performance of the LRINEC score. Finally, we performed sensitivity analyses to estimate whether missing data for c-reactive protein (CRP) results were likely to impact our results. Results Of 266 ED patients coded as having a discharge diagnosis of NF, we were able to confirm the diagnosis, by chart review, in 167. We were able to calculate a LRINEC score in only 80 patients (due to absence of an initial CRP value); an LRINEC score of 6 or greater had a sensitivity of 77%. Sensitivity analyses of missing data supported our finding of inadequate sensitivity to rule out NF. In sub-analysis, NF patients with concurrent diabetes were more likely to be accurately categorized by the LRINEC score. Conclusion Used in isolation, the LRINEC score is not sufficiently sensitive to rule out NF in a general ED population. PMID:27330667

  11. 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.

  12. Pain Sensitivity in Adolescent Males with Attention-Deficit/Hyperactivity Disorder: Testing for Associations with Conduct Disorder and Callous and Unemotional Traits

    PubMed Central

    Northover, Clare; Thapar, Anita; Langley, Kate; van Goozen, Stephanie HM

    2015-01-01

    Background Reduced processing and experience of aversive emotional cues is a common component of theories on the development and persistence of aggression and antisocial behaviour. Yet physical pain, arguably the most basic aversive cue, has attracted comparatively little attention. Methods This study measured pain sensitivity and physiological response to painful stimuli (skin conductance level, SCL) in adolescent boys with Attention-Deficit/Hyperactivity Disorder (ADHD; n = 183), who are at high risk for antisocial behaviour. We compared boys with ADHD with and without a comorbid diagnosis of Conduct Disorder (CD) on pain sensitivity, and examined patterns of association between pain measures, on the one hand, and problem severity and callous and unemotional (CU) traits, on the other. Results Boys with comorbid CD exhibited a higher pain threshold and tolerance than boys with ADHD alone, but the groups did not differ in physiology at the time the pain threshold and tolerance were reported. Regression analyses showed that ADHD problem severity positively predicted pain sensitivity, whereas levels of CU traits negatively predicted pain sensitivity. Conclusions These findings on physical pain processing extend evidence of impairments in aversive cue processing among those at risk of antisocial behaviour. The study highlights the importance of considering comorbidity and heterogeneity of disorders when developing interventions. The current findings could be used to identify subgroups within those with ADHD who might be less responsive to interventions that use corrective feedback to obtain behaviour change. PMID:26225935

  13. Awareness is awareness is awareness? Decomposing different aspects of awareness and their role in operant learning of pain sensitivity.

    PubMed

    Becker, Susanne; Kleinböhl, Dieter; Hölzl, Rupert

    2012-09-01

    Regarding awareness as a consistent concept has contributed to the controversy about implicit learning. The present study emphasized the importance of distinguishing aspects of awareness in order to determine whether learning is implicit. By decomposing awareness into awareness of contingencies, of the procedure being a learning task, and of the reinforcing stimuli, it was demonstrated that implicit operant learning modulated pain sensitivity. All of these aspects of awareness were demonstrated to not be necessary for learning. Additionally, discrimination of contingencies was not necessary on different levels of processing as demonstrated by a verbal and a behavioral method. It was demonstrated that explicit cognitive processes about one's own behavior, impaired learning, even though these cognitions were not immediately related to the learning process. The results of this study are of special interest in the context of pain, since implicit operant learning can explain the gradual development of hypersensitivity in chronic pain.

  14. Sensitivity and Specificity of Reliable Digit Span in Malingered Pain-Related Disability

    ERIC Educational Resources Information Center

    Etherton, Joseph L.; Bianchini, Kevin J.; Greve, Kevin W.; Heinly, Matthew T.

    2005-01-01

    The reliable digit span (RDS) performance of chronic pain patients with unambiguous spinal injuries and no evidence of exaggeration or response bias (n = 53) was compared to that of chronic pain patients meeting criteria for definite malingered neurocognitive dysfunction (n = 35), and a group of nonmalingering moderate-severe traumatic brain…

  15. Sensitivity and specificity of cytodiagnosis of body fluids in a laboratory of urgencies.

    PubMed

    Rocher, A E; Guerra, F; Rofrano, J; Angeleri, A; Canessa, O E; Mendeluk, G R; Palaoro, L A

    2011-10-01

    The main purpose for studying cytological body fluids is confirmation of a benign or malignant effusion. Our cytology laboratory analyzes body fluids and results are requested urgently. The samples are stained by the Giemsa and Papanicolaou methods to give a preliminary report, then they are examined by other complementary techniques. Three hundred thirty samples of pleural and peritoneal fluids were studied to compare the sensitivity of Papanicolaou and Giemsa stains. AgNOR assay, immunocytochemistry and assessment of ploidy were used to improve the sensitivity of the cytodiagnosis. Two hundred one samples were positive, 84 negative and 45 inconclusive using the Papanicolaou stain, while 135 samples were positive, 72 negative and 123 inconclusive using Giemsa stain. The sensitivity was 79%, 53% and 83% for Papanicolaou, Giemsa, and both techniques together, respectively. Using complementary techniques, the sensitivity reached 95% for AgNOR, 87% for tumor markers (panel), and 92% for Ploidy. There were no false positive in our series; therefore specificity was 100%. The use of both Papanicolaou and Giemsa in conjunction increased the sensitivity of the cytodiagnosis in body fluids. The complementary methods, especially AgNOR assay and assessment of ploidy, diminished the number of inconclusive cases.

  16. Comparative sensitivity of field and laboratory populations of Hyalella azteca to the pyrethroid insecticides bifenthrin and cypermethrin.

    PubMed

    Clark, Stephen L; Ogle, R Scott; Gantner, Andrew; Hall, Lenwood W; Mitchell, Gary; Giddings, Jeffrey; McCoole, Matthew; Dobbs, Michael; Henry, Kevin; Valenti, Ted

    2015-10-01

    Hyalella azteca are epibenthic invertebrates that are widely used for toxicity studies. They are reported to be more sensitive to pyrethroid insecticides than most other test species, which has prompted considerable use of this species in toxicity testing of ambient surface waters where the presence of pyrethroids is suspected. However, resident H. azteca have been found in some ambient water bodies reported to contain surface water and/or sediment pyrethroid concentrations that are toxic to laboratory reared H. azteca. This observation suggests differences in the sensitivities of laboratory reared and field populations of H. azteca to pyrethroids. The goal of the present study was to determine the sensitivities of laboratory reared and field populations of H. azteca to the pyrethroids bifenthrin and cypermethrin. Specimens of H. azteca were collected from resident populations at field sites that are subject to varied land-use activities as well as from laboratory populations. These organisms were exposed to bifenthrin- or cypermethrin-spiked water in 96-h water-only toxicity tests. The resulting data demonstrated that: 1) field-collected populations in urban and agricultural settings can be >2 orders of magnitude less sensitive to the pyrethroids than laboratory reared organisms; 2) field-collected organisms varied in their sensitivity (possibly based on land-use activities), with organisms collected from undeveloped sites exhibiting sensitivities similar to laboratory reared organisms; and 3) the sensitivity of field-collected "tolerant" organisms increased in subsequent generations reared under laboratory conditions. Potential mechanisms for these differences are discussed.

  17. The effect of bacteria on the sensitivity of microalgae to copper in laboratory bioassays.

    PubMed

    Levy, Jacqueline L; Stauber, Jenny L; Wakelin, Steven A; Jolley, Dianne F

    2009-03-01

    Although single-species laboratory toxicity tests with microalgae are sensitive and highly reproducible, they lack environmental realism. Interactions between algae and their associated bacteria, either in the plankton or in biofilms, may alter algal sensitivity to contaminants, which are not mimicked in laboratory toxicity tests. This study investigated the effects of simple algal-bacterial relationships on the sensitivity of laboratory-cultured algae to copper using 72-h algal growth-rate inhibition bioassays. Four species of microalgae were used, two isolates of each; a strain of algae with no microscopically visible and no culturable bacteria present (operationally defined as axenic) and a non-axenic strain. The four algae used were the marine diatom Nitzschia closterium, the freshwater green alga Pseudokirchneriella subcapitata and two tropical Chlorella spp. Under control conditions (no copper), N. closterium and P. subcapitata grew better in the presence of the bacterial community. Sensitivity to copper (assessed as the concentration to inhibit the growth rate by 50% after 72-h (IC50)) was not significantly different for the axenic and non-axenic strains of N. closterium, P. subcapitata or for Chlorella sp. (PNG isolate). At pH 5.7, the axenic Chlorella sp. (NT isolate) had a 72-h IC50 of 46mugCuL(-1), while in the presence of bacteria the IC50 increased (i.e., sensitivity decreased) to 208mugCuL(-1). However, when the bacterial status of both the operationally defined axenic and non-axenic cultures of N. closterium and Chlorella sp. (NT isolate) was investigated using polymerase chain reaction (PCR) amplification of 16S rRNA followed by DNA fingerprinting using denaturing gradient gel electrophoresis (DGGE), it was found that bacteria were actually present in all the algal cultures, i.e. the axenic cultures were not truly bacteria-free. Based on sequence information, the bacteria present were nearly all identified as alphaproteobacteria, and a number of

  18. 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 ...

  19. Central and peripheral pain generators in women with chronic pelvic pain: patient centered assessment and treatment.

    PubMed

    Hoffman, Donna

    2015-01-01

    Women with chronic pelvic pain (CPP) often present without obvious cause on imaging studies, laboratory values or physical exam. Dysfunctional sensory processing in the central nervous system (CNS) may explain pain of unclear origin. Central sensitization (CS), a mechanism of centrally mediated pain, describes this abnormal processing of sensory information. Women with CPP often present with several seemingly unrelated symptoms. This can be explained by co-existing chronic pain syndromes occurring in the same patient. Central sensitization occurs in all of these pain syndromes, also described as dysfunctional pain syndromes, and thus may explain why several often occur in the same patient. Six of the most common pain disorders that co-exist in CPP include endometriosis, painful bladder syndrome/interstitial cysitis, vulvodynia, myofascial pain/ pelvic floor hypertonus, irritable bowel syndrome, and primary dysmenorrhea. Central pain generators, (pain originating from CS) and peripheral pain generators, (pain from local tissue damage), can both occur in each of these six conditions. These pain generators will be described. Chronic pain, specifically dysfunctional sensory processing, is recognized as a systemic disease process like diabetes to be managed as opposed to a local problem to be "fixed" or cured. A multi-disciplinary approach to assessment and treatment with a focus on improving emotional, physical and social functioning instead of focusing strictly on pain reduction is more effective in decreasing disability. This is best achieved by determining the patient's needs and perspective through a patient-centered approach. Algorithms for such an approach to assessment and treatment are outlined.

  20. Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat.

    PubMed

    Omerbašić, Damir; Smith, Ewan St J; Moroni, Mirko; Homfeld, Johanna; Eigenbrod, Ole; Bennett, Nigel C; Reznick, Jane; Faulkes, Chris G; Selbach, Matthias; Lewin, Gary R

    2016-10-11

    The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness.

  1. 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.

  2. Evidence for a role of NTS2 receptors in the modulation of tonic pain sensitivity

    PubMed Central

    Roussy, Geneviève; Dansereau, Marc-André; Baudisson, Stéphanie; Ezzoubaa, Faouzi; Belleville, Karine; Beaudet, Nicolas; Martinez, Jean; Richelson, Elliott; Sarret, Philippe

    2009-01-01

    Background Central neurotensin (NT) administration results in a naloxone-insensitive antinociceptive response in animal models of acute and persistent pain. Both NTS1 and NTS2 receptors were shown to be required for different aspects of NT-induced analgesia. We recently demonstrated that NTS2 receptors were extensively associated with ascending nociceptive pathways, both at the level of the dorsal root ganglia and of the spinal dorsal horn. Then, we found that spinally administered NTS2-selective agonists induced dose-dependent antinociceptive responses in the acute tail-flick test. In the present study, we therefore investigated whether activation of spinal NTS2 receptors suppressed the persistent inflammatory pain symptoms observed after intraplantar injection of formalin. Results We first demonstrated that spinally administered NT and NT69L agonists, which bind to both NTS1 and NTS2 receptors, significantly reduced pain-evoked responses during the inflammatory phase of the formalin test. Accordingly, pretreatment with the NTS2-selective analogs JMV-431 and levocabastine was effective in inhibiting the aversive behaviors induced by formalin. With resolution at the single-cell level, we also found that activation of spinal NTS2 receptors reduced formalin-induced c-fos expression in dorsal horn neurons. However, our results also suggest that NTS2-selective agonists and NTS1/NTS2 mixed compounds differently modulated the early (21–39 min) and late (40–60 min) tonic phase 2 and recruited endogenous pain inhibitory mechanisms integrated at different levels of the central nervous system. Indeed, while non-selective drugs suppressed pain-related behaviors activity in both part of phase 2, intrathecal injection of NTS2-selective agonists was only efficient in reducing pain during the late phase 2. Furthermore, assessment of the stereotypic pain behaviors of lifting, shaking, licking and biting to formalin also revealed that unlike non-discriminative NTS1/NTS2 analogs

  3. Influence of topical capsaicin on facial sensitivity in response to experimental pain.

    PubMed

    Lee, Y-S; Kho, H-S; Kim, Y-K; Chung, S-C

    2007-01-01

    Capsaicin, the pungent component of the red pepper, has been used as an analgesic in a variety of pain conditions, but sensory impairment after long-term treatment has been concerned. This study investigated the influence of topical capsaicin on various types of sensations including pain in the facial areas innervated by the mental nerve, and also evaluated whether the measurement of cutaneous current perception threshold (CPT) is reliable for the quantification of sensory change following capsaicin application. Twenty healthy subjects were given topical capsaicin cream (0.075%), which was applied to the mental area unilaterally, four times daily for 2 weeks. Burning sensation after capsaicin application gradually decreased with repeated applications. Repeated topical capsaicin resulted in reduced sensation to mechanical, heat and cold pain without changing non-painful tactile sensation. It also resulted in increased CPTs at 5 Hz and 250 Hz stimuli but no change in the CPTs at 2000 Hz from the first evaluation after capsaicin treatment and throughout the treatment period. This study demonstrated that topical capsaicin treatment for the management of chronic localized pain can be safely applied to the face without affecting non-painful normal sensations, and that CPT testing is a clinically useful tool for the quantification of sensory changes following capsaicin application.

  4. Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury

    PubMed Central

    Carlton, Susan M.; Du, Junhui; Tan, Huai Yu; Nesic, Olivera; Hargett, Gregory L.; Bopp, Anne C.; Yamani, Ammar; Lin, Qing; Willis, William D.; Hulsebosch, Claire E.

    2009-01-01

    Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of above-level CNP. Following a thoracic (T10) contusion, forelimb nociceptors had enhanced spontaneous activity and were sensitized to mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical dorsal horn neurons showed enhanced responses to non-noxious and noxious mechanical stimulation as well as thermal stimulation of receptive fields. Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal damage as a cause for above-level sensitization since few C8 DRG cells expressed AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally, activated microglia and astrocytes were present in thoracic and cervical cord at 35 days post-SCI, indicating a rostral spread of glial activation from the injury site. Based on these data, we conclude that peripheral and central sensitization as well as reactive glia in the uninjured cervical cord contribute to CNP. We hypothesize that reactive glia in the cervical cord release pro-inflammatory substances which drive chronic CNP. Thus a complex cascade of events spanning many cord segments underlies above-level CNP. PMID:19853381

  5. Intrathecal PKA-selective siRNA treatment blocks sustained morphine-mediated pain sensitization and antinociceptive tolerance in rats.

    PubMed

    Tumati, S; Roeske, W R; Largent-Milnes, T M; Vanderah, T W; Varga, E V

    2011-07-15

    Sustained morphine treatment has been shown to produce paradoxical pain sensitization (opioid-induced hyperalgesia) and also causes increase in spinal pain neurotransmitter, such as calcitonin gene related peptide (CGRP), concentration in experimental animals. Studies have also shown that cyclic adenosine-monophosphate (cAMP)-dependent protein kinase (PKA) plays a major role in the regulation of presynaptic neurotransmitter (such as CGRP and substance P) synthesis and release. We have previously shown that in cultured primary sensory dorsal root ganglion (DRG) neurons sustained in vitro opioid agonist treatment upregulates cAMP levels (adenylyl cyclase (AC) superactivation) and augments basal and capsaicin evoked CGRP release in a PKA dependent manner. In the present study, we investigated the in vivo role of PKA in sustained morphine-mediated pain sensitization. Our data indicate that selective knock-down of spinal PKA activity by intrathecal (i.th.) pretreatment of rats with a PKA-selective small interference RNA (siRNA) mixture significantly attenuates sustained morphine-mediated augmentation of spinal CGRP immunoreactivity, thermal hyperalgesia, mechanical allodynia and antinociceptive tolerance. The present findings indicate that sustained morphine-mediated activation of spinal cAMP/PKA-dependent signaling may play an important role in opioid induced hyperalgesia.

  6. A randomized study of the effect of oral lamotrigine and hydromorphone on pain and hyperalgesia following heat/capsaicin sensitization.

    PubMed

    Petersen, Karin L; Maloney, Alan; Hoke, Frank; Dahl, Jørgen B; Rowbotham, Michael C

    2003-09-01

    In this randomized double-blind placebo-controlled study, the analgesic effect of oral lamotrigine (400 mg) on cutaneous sensitization induced with the heat/capsaicin sensitization model was compared with the effect of oral hydromorphone (8 mg) in healthy volunteers. In a separate session, intravenous remifentanil (0.10 microg.kg(-1).min(-1)) and placebo were administered. This session was used as an additional reference comparator. Outcome measures were the areas of secondary hyperalgesia to brush and von Frey hair stimulation and the painfulness of noxious thermal stimulation in nonsensitized skin. Compared with placebo, both intravenous remifentanil and oral hydromorphone significantly suppressed secondary hyperalgesia and acute thermal nociception. Oral lamotrigine did not reduce secondary hyperalgesia or acute thermal nociception but produced side effects of severity comparable with that of oral hydromorphone. Although lamotrigine is efficacious in the management of some types of chronic neuropathic pain, the lack of effect of this agent on human experimental pain suggests that its analgesic effects depend on nerve injury-associated abnormalities, which cannot be simulated in healthy human volunteers.

  7. Sensitivity of rainfall-runoff processes in the Hydrological Open Air Laboratory

    NASA Astrophysics Data System (ADS)

    Széles, Borbála; Parajka, Juraj; Blöschl, Günter; Oismüller, Markus; Hajnal, Géza

    2016-04-01

    The objective of the present study was to simulate the rainfall response and analyse the sensitivity of rainfall-runoff processes of the Hydrological Open Air Laboratory (HOAL) in Petzenkirchen, a small experimental watershed (66 ha) located in the western part of Lower Austria and dominated by agricultural land use. Due to the extensive monitoring network in the HOAL, the spatial and temporal heterogeneity of hydro-meteorological elements are exceptionally well represented on the catchment scale. The study aimed to exploit the facilities of the available database collected by innovative sensing techniques to advance the understanding of various rainfall-runoff processes. The TUWmodel, a lumped, conceptual hydrological model, following the structure of the HBV model was implemented on the catchment. In addition to the surface runoff at the catchment outlet, several different runoff generation mechanisms (tile drainage flow, saturation excess runoff from wetlands and groundwater discharge from springs) were also simulated, which gave an opportunity to describe the spatial distribution of model parameters in the study area. This helped to proceed from the original lumped model concept towards a spatially distributed one. The other focus of this work was to distinguish the dominant model parameters from the less sensitive ones for each tributary with different runoff type by applying two different sensitivity analysis methods, the simple local perturbation and the global Latin-Hypercube-One-Factor-At-a-Time (LH-OAT) tools. Moreover, the impacts of modifying the initial parameters of the LH-OAT method and the applied objective functions were also taken into consideration. The results and findings of the model and sensitivity analyses were summarized and future development perspectives were outlined. Key words: spatial heterogeneity of rainfall-runoff mechanisms, sensitivity analysis, lumped conceptual hydrological model

  8. 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

  9. Single-point but not tonic cuff pressure pain sensitivity is associated with level of physical fitness--a study of non-athletic healthy subjects.

    PubMed

    Lemming, Dag; Börsbo, Björn; Sjörs, Anna; Lind, Eva-Britt; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas; Gerdle, Björn

    2015-01-01

    Exercise is often used for pain rehabilitation but the link between physical activity level and pain sensitivity is still not fully understood. Pressure pain sensitivity to cuff algometry and conditioned pain modulation (CPM) were evaluated in highly active men (n=22), normally active men (n=26), highly active women (n=27) and normally active women (n=23) based on the Godin Leisure-Time Exercise Questionnaire. Cuff pressure pain sensitivity was assessed at the arm and lower leg. The subjects scored the pain intensity on an electronic Visual Analogue Scale (VAS) during ten minutes with 25 kPa constant cuff pressure and two minutes with zero pressure. The maximal VAS score and area under the VAS-curve were extracted. Pressure pain thresholds (PPT) were recorded by manual pressure algometry on the ipsilateral tibialis anterior muscle before, during and after the tonic arm stimulation. Tonic cuff stimulation of the arm and leg resulted in higher VAS peak scores in women compared with men (p<0.04). In all groups the PPTs were reduced during and after the cuff stimulation compared with baseline (p=0.001). PPT were higher in men compared with women (p=0.03) and higher in highly physical active compared with normal active (p=0.048). Besides the well-known gender difference in pressure pain sensitivity this study demonstrates that a high physical fitness degree in non-athletic subjects is associated with increased pressure pain thresholds but does not affect cuff pressure pain sensitivity in healthy people.

  10. Laboratory evaluation of an airborne ozone instrument that compensates for altitude/sensitivity effects

    NASA Technical Reports Server (NTRS)

    Gregory, G. L.; Hudgins, C. H.; Edahl, R. A., Jr.

    1983-01-01

    One problem encountered in the use of air-quality instrumentation on aircraft is the variation of instrument sensitivity with pressure as the result of altitude changes of the aircraft. Many instruments experience sensitivity changes of as much as a factor of 2 at altitudes of 6 km. Discussed are recent modifications to a chemiluminescent (ethylene) ozone detector that allow the instrument to automatically compensate for pressure/sensitivity effects. The modification provides automated mass flow rate control for both the sample and ethylene gas flows. The flow control systems maintain flow rate to within 15 percent for a 100-torr instantaneous pressure change, and flow rates are returned to the desired set points within 10 s after the pressure change. During simulated altitude changes (300 m/min from mean sea level to 3-km altitude), flow rates were controlled to within 3 percent of the set point. Laboratory data are summarized verifying the operation of the instrument for a pressure range of 760 torr (sea level) to 350 torr (approximately 20,000 ft) and an ozone concentration range from 20 to approximately 700 ppb.

  11. Increased sensitivity to physical activity among individuals with knee osteoarthritis: relation to pain outcomes, psychological factors, and responses to quantitative sensory testing.

    PubMed

    Wideman, Timothy H; Finan, Patrick H; Edwards, Robert R; Quartana, Phillip J; Buenaver, Luis F; Haythornthwaite, Jennifer A; Smith, Michael T

    2014-04-01

    Recent findings suggest that certain individuals with musculoskeletal pain conditions have increased sensitivity to physical activity (SPA) and respond to activities of stable intensity with increasingly severe pain. This study aimed to determine the degree to which individuals with knee osteoarthritis (OA) show heightened SPA in response to a standardized walking task and whether SPA cross-sectionally predicts psychological factors, responses to quantitative sensory testing (QST), and different OA-related outcomes. One hundred seven adults with chronic knee OA completed self-report measures of pain, function, and psychological factors, underwent QST, and performed a 6-min walk test. Participants rated their discomfort levels throughout the walking task; an index of SPA was created by subtracting first ratings from peak ratings. Repeated-measure analysis of variance revealed that levels of discomfort significantly increased throughout the walking task. A series of hierarchical regression analyses determined that after controlling for significant covariates, psychological factors, and measures of mechanical pain sensitivity, individual variance in SPA predicted self-report pain and function and performance on the walking task. Analyses also revealed that both pain catastrophizing and the temporal summation of mechanical pain were significant predictors of SPA and that SPA mediated the relationship between catastrophizing and self-reported pain and physical function. The discussion addresses the potential processes contributing to SPA and the role it may play in predicting responses to different interventions for musculoskeletal pain conditions.

  12. Revised Reinforcement Sensitivity Theory and Laboratory Assessment of BIS and BAS in Children.

    PubMed

    Colder, Craig R; Trucco, Elisa M; Lopez, Hector I; Hawk, Larry W; Read, Jennifer P; Lengua, Liliana J; Weiczorek, William F; Eiden, Rina D

    2011-04-01

    There is considerable interest in Gray's reinforcement sensitivity theory. However, few measures of the behavioral approach (BAS) and inhibition systems (BIS) exist for children. Moreover, the theory was substantially revised a decade ago and measurement instruments are still largely based on the old theory. Our aim was to revise questionnaire and laboratory assessments of BIS and BAS for children. Performance on the Point Scoring Reaction Time Task for Children Revised (PSRTT-CR) conformed to theoretical expectations. Caregiver reports of BIS and BAS were associated with corresponding PSRTT-CR indices, suggesting cross-method convergent and discriminant validity. There was convergence with physiological correlates of BAS, but not physiological correlates of BIS. Overall, our revised measures represent promising instruments of children's BIS and BAS.

  13. Intense pain influences the cortical processing of visual stimuli projected onto the sensitized skin

    PubMed Central

    Torta, DM; Van Den Broeke, EN; Filbrich, L; Jacob, B; Lambert, J; Mouraux, A

    2017-01-01

    Sensitization is a form of implicit learning produced by the exposure to a harmful stimulus. In humans and other mammals, sensitization following skin injury increases the responsiveness of peripheral nociceptors, and enhances the synaptic transmission of nociceptive input in the central nervous system (CNS). Here, we show that sensitization-related changes in the CNS are not restricted to nociceptive pathways and, instead, also affect other sensory modalities, especially if that modality conveys information relevant for the sensitized body part. Specifically, we show that after sensitizing the forearm using high-frequency electrical stimulation of the skin (HFS), visual stimuli projected onto the sensitized forearm elicit significantly enhanced brain responses. Whereas mechanical hyperalgesia was present both 20 and 45 minutes after HFS, the enhanced responsiveness to visual stimuli was present only 20 minutes after HFS. Taken together, our results indicate that sensitization involves both nociceptive-specific and multimodal mechanisms, having distinct time courses. PMID:28030473

  14. Changes in Midbrain Pain Receptor Expression, Gait and Behavioral Sensitivity in a Rat Model of Radiculopathy

    PubMed Central

    Hwang, Priscilla Y; Allen, Kyle D; Shamji, Mohammed F; Jing, Liufang; Mata, Brian A; Gabr, Mostafa A; Huebner, Janet L; Kraus, Virginia B; Richardson, William J; Setton, Lori A

    2012-01-01

    Intervertebral disc herniation may contribute to inflammatory processes that associate with radicular pain and motor deficits. Molecular changes at the affected dorsal root ganglion (DRG), spinal cord, and even midbrain, have been documented in rat models of radiculopathy or nerve injury. The objective of this study was to evaluate gait and the expression of key pain receptors in the midbrain in a rodent model of radiculopathy. Radiculopathy was induced by harvesting tail nucleus pulposus (NP) and placing upon the right L5 DRG in rats (NP-treated, n=12). Tail NP was discarded in sham-operated animals (n=12). Mechanical allodynia, weight-bearing, and gait were evaluated in all animals over time. At 1 and 4 weeks after surgery, astrocyte and microglial activation was tested in DRG sections. Midbrain sections were similarly evaluated for immunoreactivity to serotonin (5HT2B), mu-opioid (µ-OR), and metabotropic glutamate (mGluR4 and 5) receptor antibodies. NP-treated animals placed less weight on the affected limb 1 week after surgery and experienced mechanical hypersensitivity over the duration of the study. Astroctye activation was observed at DRGs only at 4 weeks after surgery. Findings for pain receptors in the midbrain of NP-treated rats included an increased expression of 5HT2B at 1, but not 4 weeks; increased expression of µ-OR and mGluR5 at 1 and 4 weeks (periaqueductal gray region only); and no changes in expression of mGluR4 at any point in this study. These observations provide support for the hypothesis that the midbrain responds to DRG injury with a transient change in receptors regulating pain responses. PMID:22962568

  15. Social defeat stress potentiates thermal sensitivity in operant models of pain processing

    PubMed Central

    Marcinkiewcz, Catherine A.; Green, Megan K.; Devine, Darragh P.; Duarte, Peter; Vierck, Charles J.; Yezierski, Robert P.

    2013-01-01

    Higher-order processing of nociceptive input is distributed in corticolimbic regions of the brain, including the anterior cingulate, parieto-insular and prefrontal cortices, as well as subcortical structures such as the bed nucleus of stria terminalis and amygdala. In addition to their role in pain processing, these regions encode or modulate emotional, motivational and sensory responses to stress. Thus, pain and stress pathways in the brain intersect at cortical and subcortical forebrain structures. Accordingly, previous work has shown that acute restraint stress in female rats induces heat hyperalgesia in a forebrain-dependent operant test of thermal escape. In the present study, we investigated the effects of social defeat stress in male rats on the operant escape task, as well as in a test of nociceptive thermal preference. After establishing baseline behaviors in these tests, separate groups of rats were socially defeated by dominant “resident” male rats. They were tested for thermal preference after 5 successive social defeat sessions. Escape from cold, heat and a neutral warm temperature also was evaluated after social defeat. Defeated rats exhibited a significant increase in cold preference after social defeat compared to the baseline. In the escape task, the rats exhibited increased escape from warm and nociceptive cold and heat temperatures. Thus, chronic social stress produces hyperalgesia for both hot and cold stimuli in male rats, suggesting a mutually facilitatory cross-regulation between central pathways regulating stress and pain. PMID:19059227

  16. Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain.

    PubMed

    Wang, Shenglan; Dai, Yi; Fukuoka, Tetsuo; Yamanaka, Hiroki; Kobayashi, Kimiko; Obata, Koichi; Cui, Xiuyu; Tominaga, Makoto; Noguchi, Koichi

    2008-05-01

    Bradykinin is an inflammatory mediator that plays a pivotal role in pain and hyperalgesia in inflamed tissues by exciting and/or sensitizing nociceptors. TRPA1 is an important component of the transduction machinery through which environmental irritants and endogenous proalgesic agents depolarize nociceptors to elicit inflammatory pain. Here, using electrophysiological, immunocytochemical and behavioural analyses, we showed a functional interaction of these two inflammation-related molecules in both heterologous expressing systems and primary sensory neurons. We found that bradykinin increased the TRPA1 currents evoked by allyl isothiocyanate (AITC) or cinnamaldehyde in HEK293 cells expressing TRPA1 and bradykinin receptor 2 (B2R). This potentiation was inhibited by phospholipase C (PLC) inhibitor or protein kinase A (PKA) inhibitor, and mimicked by PLC or PKA activator. The functional interaction between B2R and TRPA1, as well as the modulation mechanism, was also observed in rat dorsal root ganglia neurons. In an occlusion experiment, the PLC activator could enhance AITC-induced TRPA1 current further even in saturated PKA-mediated potentiation, indicating the additive potentiating effects of the PLC and PKA pathways. These data for the first time indicate that a cAMP-PKA signalling is involved in the downstream from B2R in dorsal root ganglia neurons in addition to PLC. Finally, subcutaneous pre-injection of a sub-inflammatory dose of bradykinin into rat hind paw enhanced AITC-induced pain behaviours, which was consistent with the observations in vitro. Collectively, these results represent a novel mechanism through which bradykinin released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.

  17. Botulinum toxin type A selectivity for certain types of pain is associated with capsaicin-sensitive neurons.

    PubMed

    Matak, Ivica; Rossetto, Ornella; Lacković, Zdravko

    2014-08-01

    Unlike most classical analgesics, botulinum toxin type A (BoNT/A) does not alter acute nociceptive thresholds, and shows selectivity primarily for allodynic and hyperalgesic responses in certain pain conditions. We hypothesized that this phenomenon might be explained by characterizing the sensory neurons targeted by BoNT/A in the central nervous system after its axonal transport. BoNT/A's central antinociceptive activity following its application into the rat whisker pad was examined in trigeminal nucleus caudalis (TNC) and higher-level nociceptive brain areas using BoNT/A-cleaved synaptosomal-associated protein 25 (SNAP-25) and c-Fos immunohistochemistry. Occurrence of cleaved SNAP-25 in TNC was examined after nonselective ganglion ablation with formalin or selective denervation of capsaicin-sensitive (vanilloid receptor-1 or TRPV1-expressing) neurons, and in relation to different cellular and neuronal markers. Regional c-Fos activation and effect of TRPV1-expressing afferent denervation on toxin's antinociceptive action were studied in formalin-induced orofacial pain. BoNT/A-cleaved SNAP-25 was observed in TNC, but not in higher-level nociceptive nuclei. Cleaved SNAP-25 in TNC disappeared after formalin-induced trigeminal ganglion ablation or capsaicin-induced sensory denervation. Occurrence of cleaved SNAP-25 in TNC and BoNT/A antinociceptive activity in formalin-induced orofacial pain were prevented by denervation with capsaicin. Cleaved SNAP-25 localization demonstrated toxin's presynaptic activity in TRPV1-expressing neurons. BoNT/A reduced the c-Fos activation in TNC, locus coeruleus, and periaqueductal gray. Present experiments suggest that BoNT/A alters the nociceptive transmission at the central synapse of primary afferents. Targeting of TRPV1-expressing neurons might be associated with observed selectivity of BoNT/A action only in certain types of pain.

  18. Experimental Realisation of High-sensitivity Laboratory X-ray Grating-based Phase-contrast Computed Tomography

    NASA Astrophysics Data System (ADS)

    Birnbacher, Lorenz; Willner, Marian; Velroyen, Astrid; Marschner, Mathias; Hipp, Alexander; Meiser, Jan; Koch, Frieder; Schröter, Tobias; Kunka, Danays; Mohr, Jürgen; Pfeiffer, Franz; Herzen, Julia

    2016-04-01

    The possibility to perform high-sensitivity X-ray phase-contrast imaging with laboratory grating-based phase-contrast computed tomography (gbPC-CT) setups is of great interest for a broad range of high-resolution biomedical applications. However, achieving high sensitivity with laboratory gbPC-CT setups still poses a challenge because several factors such as the reduced flux, the polychromaticity of the spectrum, and the limited coherence of the X-ray source reduce the performance of laboratory gbPC-CT in comparison to gbPC-CT at synchrotron facilities. In this work, we present our laboratory X-ray Talbot-Lau interferometry setup operating at 40 kVp and describe how we achieve the high sensitivity yet unrivalled by any other laboratory X-ray phase-contrast technique. We provide the angular sensitivity expressed via the minimum resolvable refraction angle both in theory and experiment, and compare our data with other differential phase-contrast setups. Furthermore, we show that the good stability of our high-sensitivity setup allows for tomographic scans, by which even the electron density can be retrieved quantitatively as has been demonstrated in several preclinical studies.

  19. Experimental Realisation of High-sensitivity Laboratory X-ray Grating-based Phase-contrast Computed Tomography

    PubMed Central

    Birnbacher, Lorenz; Willner, Marian; Velroyen, Astrid; Marschner, Mathias; Hipp, Alexander; Meiser, Jan; Koch, Frieder; Schröter, Tobias; Kunka, Danays; Mohr, Jürgen; Pfeiffer, Franz; Herzen, Julia

    2016-01-01

    The possibility to perform high-sensitivity X-ray phase-contrast imaging with laboratory grating-based phase-contrast computed tomography (gbPC-CT) setups is of great interest for a broad range of high-resolution biomedical applications. However, achieving high sensitivity with laboratory gbPC-CT setups still poses a challenge because several factors such as the reduced flux, the polychromaticity of the spectrum, and the limited coherence of the X-ray source reduce the performance of laboratory gbPC-CT in comparison to gbPC-CT at synchrotron facilities. In this work, we present our laboratory X-ray Talbot-Lau interferometry setup operating at 40 kVp and describe how we achieve the high sensitivity yet unrivalled by any other laboratory X-ray phase-contrast technique. We provide the angular sensitivity expressed via the minimum resolvable refraction angle both in theory and experiment, and compare our data with other differential phase-contrast setups. Furthermore, we show that the good stability of our high-sensitivity setup allows for tomographic scans, by which even the electron density can be retrieved quantitatively as has been demonstrated in several preclinical studies. PMID:27040492

  20. Effect of two consecutive spinal manipulations in a single session on myofascial pain pressure sensitivity: a randomized controlled trial

    PubMed Central

    Laframboise, Michelle A.; Vernon, Howard; Srbely, John

    2016-01-01

    Objective: To investigate the summative effect of two consecutive spinal manipulative therapy (SMT) interventions within the same session on the pain pressure sensitivity of neurosegmentally linked myofascial tissues. Methods: 26 participants were recruited and assessed for the presence of a clinically identifiable myofascial trigger point in the right infraspinatus muscle. Participants were randomly assigned to test or control group. Test group received two consecutive real cervical SMT interventions to C5–C6 segment while controls received one real SMT followed by one validated sham SMT intervention to C5–C6 segment. Participants received the two consecutive SMT interventions 30 minutes apart. Pain pressure threshold (PPT) readings were recorded at pre-SMT1 and 5, 10, 15, 20 and 25 minutes post-SMT1 and post-SMT2. PPT readings were normalized to pre-SMT1 values and averaged. Results: Repeated measures ANOVA demonstrated a significant main effect of SMT intervention [F(1,24)=8.60, p<0.05] but not group [F(1.24)=0.01] (p=0.91). Post-hoc comparisons demonstrated a statistically significant (p<0.05) increase in SMT2 versus SMT1 (18%) in the test group but not in controls (4%) (p=0.82). Conclusions: Two consecutive SMT interventions evoke significant decreases in mechanical pressure sensitivity (increased PPT) within neurosegmentally linked myofascial tissues. The antinociceptive effects of SMT may be summative and governed by a dose-response relationship in myofascial tissues. PMID:27385833

  1. [State temperature-pain sensitivity and morphological features of the skin back in patients with idiopathic scoliosis with stage III-IV].

    PubMed

    Gorbach, E N; Shchurova, E N; Kobyzev, A E; Ryabykh, S O; Ochirova, P V

    2015-03-01

    This study was aimed at revealing the features condition of thermal, pain sensitivity and morphological pattern of the skin of the human back at the apex of spinal deformity in the thoracic area in patients with idiopathic scoliosis with stage III-IV. The study included 41 adolescent with idiopathic scoliosis with stage III-IV. Temperature-pain sensitivity was studied in Th6-Th10 dermatomes on the right and the left. Biopsies (skin) for histological examination were taken intraoperatively in projection corresponding to the apex of the arc scoliosis of the spine. Significant disorders of the sensitivity to temperature and pain were found in the dermatomes to the apex of the thoracic spine deformity that were hyperesthesia, hypoesthesia, or absent thermal sensitivity. Histostrukturnye changes of the skin are significantly decreasing the thickness of the epidermis and dermis, reduction of capillaries and changing the structure of the small vessels, destruction of individual nerve fibers and free nerve endings.

  2. A novel substituted aminoquinoline selectively targets voltage-sensitive sodium channel isoforms and NMDA receptor subtypes and alleviates chronic inflammatory and neuropathic pain.

    PubMed

    Tabakoff, Boris; Ren, Wenhua; Vanderlinden, Lauren; Snell, Lawrence D; Matheson, Christopher J; Wang, Ze-Jun; Levinson, Rock; Smothers, C Thetford; Woodward, John J; Honse, Yumiko; Lovinger, David; Rush, Anthony M; Sather, William A; Gustafson, Daniel L; Hoffman, Paula L

    2016-08-05

    Recent understanding of the systems that mediate complex disease states, has generated a search for molecules that simultaneously modulate more than one component of a pathologic pathway. Chronic pain syndromes are etiologically connected to functional changes (sensitization) in both peripheral sensory neurons and in the central nervous system (CNS). These functional changes involve modifications of a significant number of components of signal generating, signal transducing and signal propagating pathways. Our analysis of disease-related changes which take place in sensory neurons during sensitization led to the design of a molecule that would simultaneously inhibit peripheral NMDA receptors and voltage sensitive sodium channels. In the current report, we detail the selectivity of N,N-(diphenyl)-4-ureido-5,7-dichloro-2-carboxy-quinoline (DCUKA) for action at NMDA receptors composed of different subunit combinations and voltage sensitive sodium channels having different α subunits. We show that DCUKA is restricted to the periphery after oral administration, and that circulating blood levels are compatible with its necessary concentrations for effects at the peripheral cognate receptors/channels that were assayed in vitro. Our results demonstrate that DCUKA, at concentrations circulating in the blood after oral administration, can modulate systems which are upregulated during peripheral sensitization, and are important for generating and conducting pain information to the CNS. Furthermore, we demonstrate that DCUKA ameliorates the hyperalgesia of chronic pain without affecting normal pain responses in neuropathic and inflammation-induced chronic pain models.

  3. Increased sensitivity of routine laboratory detection of Strongyloides stercoralis and hookworm by agar-plate culture.

    PubMed

    Jongwutiwes, S; Charoenkorn, M; Sitthichareonchai, P; Akaraborvorn, P; Putaporntip, C

    1999-01-01

    The efficacy of agar-plate culture has been evaluated for the detection of Strongyloides stercoralis and hookworm, compared with direct smear, the formalin-ether sedimentation technique and the filter-paper method. Of 1085 stool samples from the routine laboratory service at King Chulalongkorn Memorial Hospital in Bangkok, 241 samples harboured S. stercoralis, 153 hookworm and 2 Rhabditis hominis. The recovery rate of S. stercoralis by agar-plate culture is significantly superior to the other methods (P < 0.005). The ratios of positive results from the methods used to the total number of S. stercoralis-positive cases were as follows: 1:1.03 by agar-plate culture, 1:1.85 by the filter-paper method, 1:1.98 by the sedimentation technique and 1:10.48 by direct stool smear. A similar trend of the efficacy ratio of each method was obtained for hookworm detection. The characteristic furrows left by hookworm larvae, and larvae and adults of S. stercoralis could be used for preliminary species identification. Daily search for furrows on agar plates for up to 6 consecutive days resulted in an increased sensitivity for diagnosis of both S. stercoralis and hookworm infections.

  4. Performance on selected visual and auditory subtests of the Wechsler Memory Scale-Fourth Edition during laboratory-induced pain.

    PubMed

    Etherton, Joseph L; Tapscott, Brian E

    2015-01-01

    Although chronic pain patients commonly report problems with concentration and memory, recent research indicates that induced pain alone causes little or no impairment on several Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests, suggesting that cognitive complaints in chronic pain may be attributable to factors other than pain. The current studies examined potential effects of induced pain on Wechsler Memory Scale-Fourth Edition (WMS-IV) visual working memory index (VWM) subtests (Experiment 1, n = 32) and on the immediate portions of WMS-IV auditory memory (IAM) subtests (Experiment 2, n = 55). In both studies, participants were administered one of two subtests (Symbol Span or Spatial Addition for Experiment 1; Logical Memory or Verbal Paired Associates for Experiment 2) normally and were then administered the alternate subtest while experiencing either cold pressor pain induction or a nonpainful control condition. Results indicate that induced pain in nonclinical volunteers did not impair performance on either VWM or IAM performance, suggesting that pain alone does not account for complaints or deficits in these domains in chronic pain patients. Nonpainful variables such as sleep deprivation or emotional disturbance may be responsible for reported cognitive complaints in chronic pain patients.

  5. [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.

  6. The effect of experimental muscle pain on the amplitude and velocity sensitivity of jaw closing muscle spindle afferents.

    PubMed

    Masri, Radi; Ro, Jin Y; Capra, Norman

    2005-07-19

    The effect of experimental muscle pain on the amplitude and velocity sensitivity of muscle spindle primary afferent neurons in the trigeminal mesencephalic nucleus (Vmes) was examined. Extracellular recordings were made from 45 neurons designated as spindle primary- or secondary-like on the basis of their response to ramp-and-hold jaw movements. Velocity sensitivity was assessed in spindle primary-like afferents by calculating the mean dynamic index of each unit in response to three different velocities of jaw opening before and after intramuscular injection with hypertonic saline (HS, 5%, 100 microl). The amplitude sensitivity of all jaw muscle spindle afferents was assessed by calculating the mean firing rate of each unit in response to three different amplitudes of jaw openings during both the open and hold phases of the movement and with best-fit lines obtained, using linear regression analysis, before and after HS injection. The variance of the two regression lines obtained for each unit before and after the injection was compared using the coincidence test, and changes in intercept and slope were determined. Seventy-five percent of the primary-like units and 80% of the secondary-like units presented with changes in static behavior after HS injection. Thirty-six percent of the primary-like units showed changes in dynamic behavior. Injection of isotonic saline (control) did not alter the responses of the spindle afferent to jaw opening. Thus, our results demonstrate that the predominant effect of noxious stimulation was a shift in the amplitude sensitivity of both spindle primary-like and secondary-like afferents and, to a lesser extent, the velocity sensitivity of the spindle primary-like unit. In accordance with earlier studies in the cat hindlimb and neck muscles, these results suggest that the activation of masseter muscle nociceptor alters spindle afferent responses to stretch acting primarily through static gamma motor neurons.

  7. General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression.

    PubMed

    Boyer, Nelly; Dallel, Radhouane; Artola, Alain; Monconduit, Lénaïc

    2014-07-01

    Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for

  8. Adverse Social Experiences in Adolescent Rats Result in Enduring Effects on Social Competence, Pain Sensitivity and Endocannabinoid Signaling

    PubMed Central

    Schneider, Peggy; Bindila, Laura; Schmahl, Christian; Bohus, Martin; Meyer-Lindenberg, Andreas; Lutz, Beat; Spanagel, Rainer; Schneider, Miriam

    2016-01-01

    Social affiliation is essential for many species and gains significant importance during adolescence. Disturbances in social affiliation, in particular social rejection experiences during adolescence, affect an individual’s well-being and are involved in the emergence of psychiatric disorders. The underlying mechanisms are still unknown, partly because of a lack of valid animal models. By using a novel animal model for social peer-rejection, which compromises adolescent rats in their ability to appropriately engage in playful activities, here we report on persistent impairments in social behavior and dysregulations in the endocannabinoid (eCB) system. From postnatal day (pd) 21 to pd 50 adolescent female Wistar rats were either reared with same-strain partners (control) or within a group of Fischer 344 rats (inadequate social rearing, ISR), previously shown to serve as inadequate play partners for the Wistar strain. Adult ISR animals showed pronounced deficits in social interaction, social memory, processing of socially transmitted information, and decreased pain sensitivity. Molecular analysis revealed increased CB1 receptor (CB1R) protein levels and CP55, 940 stimulated [35S]GTPγS binding activity specifically in the amygdala and thalamus in previously peer-rejected rats. Along with these changes, increased levels of the eCB anandamide (AEA) and a corresponding decrease of its degrading enzyme fatty acid amide hydrolase (FAAH) were seen in the amygdala. Our data indicate lasting consequences in social behavior and pain sensitivity following peer-rejection in adolescent female rats. These behavioral impairments are accompanied by persistent alterations in CB1R signaling. Finally, we provide a novel translational approach to characterize neurobiological processes underlying social peer-rejection in adolescence. PMID:27812328

  9. Lasting Effects of Workplace Strength Training for Neck/Shoulder/Arm Pain among Laboratory Technicians: Natural Experiment with 3-Year Follow-Up

    PubMed Central

    Larsen, Anders I.; Zebis, Mette K.; Pedersen, Mogens T.; Sjøgaard, Gisela; Andersen, Lars L.

    2014-01-01

    Objectives. This study investigated long-term effects and implementation processes of workplace strength training for musculoskeletal disorders. Methods. 333 and 140 laboratory technicians from private and public sector companies, respectively, replied to a 3-year follow-up questionnaire subsequent to a 1-year randomized controlled trial (RCT) with high-intensity strength training for prevention and treatment of neck, shoulder, and arm pain. Being a natural experiment, the two participating companies implemented and modified the initial training program in different ways during the subsequent 2 years after the RCT. Results. At 3-year follow-up the pain reduction in neck, shoulder, elbow, and wrist achieved during the first year was largely maintained at both companies. However, the private sector company was rated significantly better than the public sector company in (1) training adherence, (2) training culture, that is, relatively more employees trained at the workplace and with colleagues, (3) self-reported health changes, and (4) prevention of neck and wrist pain development among initially pain-free employees. Conclusions. This natural experiment shows that strength training can be implemented successfully at different companies during working hours on a long-term basis with lasting effects on pain in neck, shoulder, and arm. PMID:24734247

  10. Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions

    PubMed Central

    Millecamps, Magali; Naso, Lina; Mori, Chisato

    2017-01-01

    Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD) and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg]) in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients. PMID:28299231

  11. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain

    PubMed Central

    Noseda, Rodrigo; Burstein, Rami

    2013-01-01

    Scientific evidence support the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. Also, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex. PMID:24347803

  12. Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition

    PubMed Central

    Niu, Katelyn; Saloman, Jami L.; Zhang, Youping; Ro, Jin Y.

    2011-01-01

    In this study, we examined whether functional subunits of the ATP-dependent K+ channel (KATP) are expressed in trigeminal ganglia (TG), which contains sensory neurons that innervate oral and facial structures. We also investigated whether direct activation of the KATP effectively attenuates mechanical hypersensitivity in the context of an acute orofacial muscle pain condition. The KATP expression in TG and behavioral studies were conducted in age matched male and female Sprague Dawley rats. RT-PCR experiments showed that the mRNAs for the inwardly rectifying pore-forming subunits, Kir6.1 and Kir6.2, as well as the regulatory sulphonylurea subunits, SUR1 and SUR2, were reliably detected in TG. Subsequent western blot analysis confirmed that proteins for all 4 subunits are expressed in TG, and showed that Kir6.2 is expressed at a significantly higher level in male TG compared to that of female rats. This observation was confirmed by the immunohistochemical demonstration of higher percentages of Kir6 positive masseter afferents in female rats. Masseteric injection of capsaicin evokes a time dependent increase in masseter sensitivity to noxious mechanical stimulation. A specific KATP agonist, pinacidil, dose-dependently attenuated the capsaicin-induced mechanical hypersensitivity in male rats. The dose of pinacidil (20µg) that completely blocked the capsaicin responses in male rats was ineffective in female rats regardless of their estrus phases. Only at the highest dose (300µg) we used, pinacidil was partially effective in female rats. Similarly, another KATP agonist, diazoxide which targets different KATP subunits also showed sex specific responses in attenuating capsaicin-induced masseter hypersensitivity. These data suggested that sex differences in functional KATP expression in TG may underlie sex specific responses to KATP agonists. The present study provided novel information on sex differences in KATP expression in TG and its contribution under an orofacial

  13. Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2.

    PubMed

    Huang, Susan M; Lee, Hyosang; Chung, Man-Kyo; Park, Una; Yu, Yin Yin; Bradshaw, Heather B; Coulombe, Pierre A; Walker, J Michael; Caterina, Michael J

    2008-12-17

    The ability to sense changes in the environment is essential for survival because it permits responses such as withdrawal from noxious stimuli and regulation of body temperature. Keratinocytes, which occupy much of the skin epidermis, are situated at the interface between the external environment and the body's internal milieu, and have long been appreciated for their barrier function against external insults. The recent discovery of temperature-sensitive transient receptor potential vanilloid (TRPV) ion channels in keratinocytes has raised the possibility that these cells also actively participate in acute temperature and pain sensation. To address this notion, we generated and characterized transgenic mice that overexpress TRPV3 in epidermal keratinocytes under the control of the keratin 14 promoter. Compared with wild-type controls, keratinocytes overexpressing TRPV3 exhibited larger currents as well as augmented prostaglandin E(2) (PGE(2)) release in response to two TRPV3 agonists, 2-aminoethoxydiphenyl borate (2APB) and heat. Thermal selection behavior and heat-evoked withdrawal behavior of naive mice overexpressing TRPV3 were not consistently altered. Upon selective pharmacological inhibition of TRPV1 with JNJ-17203212 [corrected], however, the keratinocyte-specific TRPV3 transgenic mice showed increased escape responses to noxious heat relative to their wild-type littermates. Coadministration of the cyclooxygenase inhibitor, ibuprofen, with the TRPV1 antagonist decreased inflammatory thermal hyperalgesia in transgenic but not wild-type animals. Our results reveal a previously undescribed mechanism for keratinocyte participation in thermal pain transduction through keratinocyte TRPV3 ion channels and the intercellular messenger PGE(2).

  14. Dopamine and pain sensitivity: neither sulpiride nor acute phenylalanine and tyrosine depletion have effects on thermal pain sensations in healthy volunteers.

    PubMed

    Becker, Susanne; Ceko, Marta; Louis-Foster, Mytsumi; Elfassy, Nathaniel M; Leyton, Marco; Shir, Yoram; Schweinhardt, Petra

    2013-01-01

    Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine's well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain.

  15. Dopamine and Pain Sensitivity: Neither Sulpiride nor Acute Phenylalanine and Tyrosine Depletion Have Effects on Thermal Pain Sensations in Healthy Volunteers

    PubMed Central

    Becker, Susanne; Ceko, Marta; Louis-Foster, Mytsumi; Elfassy, Nathaniel M.; Leyton, Marco; Shir, Yoram; Schweinhardt, Petra

    2013-01-01

    Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine’s well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain. PMID:24236199

  16. [Effect of corticotropin releasing factor(CRF) on somatic pain sensitivity in conscious rats: involvement of CRF1 and CRF2 receptors].

    PubMed

    Iarushkina, N I; Bagaeva, T R; Filaretova, L P

    2014-11-01

    Corticotropin-releasing factor (CRF) is involved in the regulation of pain sensitivity and can cause an analgesic effect in animals and humans. The aim of the study was to investigate the involvement of CRF1 and CRF2 receptors in CRF-induced analgesic effect (after intraperitoneal injection) on somatic pain sensitivity in conscious rats. Somatic pain sensitivity was tested by tail flick latency (tail flick test). The involvement of CRF1 and CRF2 receptors was studied by their selective antagonists NBI 27914 and astressin 2B, respectively. Systemic administration of CRF caused an increase in tail flick latency (analgesic effect). Pretreatment with NBI 27914 or astressin 2B eliminated CRF-induced analgesic effect. Besides, NBI 27914, but not astressin 2B, increased basal tail flick latency. The data obtained indicate that the analgesic effect can be mediated by both CRF1 and CRF2 receptors. CRF-1 receptor, in contrast to the CRF2 receptors, may be involved in the regulation of the basal level of pain sensitivity.

  17. Central pain.

    PubMed

    Singh, Supreet

    2014-12-01

    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

  18. 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

  19. Influence of Cytochrome P450, Family 2, Subfamily D, Polypeptide 6 (CYP2D6) polymorphisms on pain sensitivity and clinical response to weak opioid analgesics.

    PubMed

    Zahari, Zalina; Ismail, Rusli

    2014-01-01

      CYP2D6 polymorphisms show large geographical and interethnic differences. Variations in CYP2D6 activity may impact upon a patient's pain level and may contribute to interindividual variations in the response to opioids. This paper reviews the evidence on how CYP2D6 polymorphisms might influence pain sensitivity and clinical response to codeine and tramadol. For example, it is shown that (1) CYP2D6 poor metabolizers (PMs) may be less efficient at synthesizing endogenous morphine compared with other metabolizers. In contrast, ultra-rapid metabolizers (UMs) may be more efficient than other metabolizers at synthesizing endogenous morphine, thus strengthening endogenous pain modulation. Additionally, for codeine and tramadol that are bioactivated by CYP2D6, PMs may undergo no metabolite formation, leading to inadequate analgesia. Conversely, UMs may experience quicker analgesic effects but be prone to higher mu-opioid-related toxicity. The literature suggested the potential usefulness of the determination of CYP2D6 polymorphisms in elucidating serious adverse events and in preventing subsequent inappropriate selection or doses of codeine and tramadol. Notably, even though many studies investigated a possible role of the CYP2D6 polymorphisms on pain sensitivity, pharmacokinetics and pharmacodynamics of these drugs, the results of analgesia and adverse effects are conflicting. More studies are required to demonstrate genetically determined unresponsiveness and risk of developing serious adverse events for patients with pain and these should involve larger numbers of patients in different population types.

  20. Specific proteins of the trapezius muscle correlate with pain intensity and sensitivity – an explorative multivariate proteomic study of the trapezius muscle in women with chronic widespread pain

    PubMed Central

    Olausson, Patrik; Ghafouri, Bijar; Ghafouri, Nazdar; Gerdle, Björn

    2016-01-01

    Chronic widespread pain (CWP) including fibromyalgia syndrome (FMS) has a high prevalence and is associated with prominent negative consequences. CWP/FMS exhibits morphological and functional alterations in the central nervous system. The importance of peripheral factors for maintaining the central alterations are under debate. In this study, the proteins from biopsies of the trapezius muscle from 18 female CWP/FMS patients and 19 healthy female controls were analyzed. Pain intensity and pressure pain thresholds (PPT) over the trapezius muscles were registered. Twelve proteins representing five different groups of proteins were important regressors of pain intensity in CWP/FMS (R2=0.99; P<0.001). In the regression of PPT in CWP/FMS, it was found that 16 proteins representing six groups of proteins were significant regressors (R2=0.95, P<0.05). Many of the important proteins were stress and inflammation proteins, enzymes involved in metabolic pathways, and proteins associated with muscle damage, myopathies, and muscle recovery. The altered expression of these proteins may reflect both direct and indirect nociceptive/inflammatory processes as well as secondary changes. The relative importance of the identified proteins and central alterations in CWP need to be investigated in future research. Data from this and the previous study concerning the same cohorts give support to the suggestion that peripheral factors are of importance for maintaining pain aspects in CWP/FMS. PMID:27330327

  1. Heat pain detection threshold is associated with the area of secondary hyperalgesia following brief thermal sensitization: a study of healthy male volunteers

    PubMed Central

    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen; Asghar, Mohammad Sohail; Dahl, Jørgen Berg

    2017-01-01

    Introduction The area of secondary hyperalgesia following brief thermal sensitization (BTS) of the skin and heat pain detection thresholds (HPDT) may both have predictive abilities in regards to pain sensitivity and clinical pain states. The association between HPDT and secondary hyperalgesia, however, remains unsettled, and the dissimilarities in physiologic properties suggest that they may represent 2 distinctively different pain entities. The aim of this study was to investigate the association between HPDT and BTS-induced secondary hyperalgesia. Methods A sample of 121 healthy male participants was included and tested on 2 separate study days with BTS (45°C, 3 minutes), HPDT, and pain during thermal stimulation (45°C, 1 minute). Areas of secondary hyperalgesia were quantified after monofilament pinprick stimulation. The pain catastrophizing scale (PCS) and hospital anxiety and depression scale (HADS) were also applied. Results A significant association between HPDT and the size of the area of secondary hyperalgesia (p<0.0001) was found. The expected change in area of secondary hyperalgesia due to a 1-degree increase in HPDT was estimated to be −27.38 cm2, 95% confidence interval (CI) of −37.77 to −16.98 cm2, with an R2 of 0.19. Likewise, a significant association between HADS-depression subscore and area of secondary hyperalgesia (p=0.046) was found, with an estimated expected change in secondary hyperalgesia to a 1-point increase in HADS-depression subscore of 11 cm2, 95% CI (0.19–21.82), and with R2 of 0.03. We found no significant associations between secondary hyperalgesia area and PCS score or pain during thermal stimulation. Conclusion HPDT and the area of secondary hyperalgesia after BTS are significantly associated; however, with an R2 of only 19%, HPDT only offers a modest explanation of the inter-participant variation in the size of the secondary hyperalgesia area elicited by BTS. PMID:28184167

  2. Redox-sensitivity and mobility of selected pharmaceutical compounds in a laboratory column experiment

    NASA Astrophysics Data System (ADS)

    Banzhaf, S.; Nödler, K.; Licha, T.; Krein, A.; Scheytt, T.

    2012-04-01

    Laboratory column experiments are suitable to investigate the sediment water interaction and to study the transport behaviour of solutes. Processes like retardation and degradation can be identified and quantified. The conducted experiment, which is closely connected to a field study in Luxembourg, investigated the transport behaviour of selected pharmaceutical compounds and their redox-dependent metabolism under water saturated conditions. Fine-grained natural sediment with a low hydraulic conductivity from a study site in Luxembourg was filled into the column. The water for the experiment was taken from a small stream at the same fieldsite. It was spiked with four pharmaceutical compounds (carbamazepine, diclofenac, ibuprofen, sulfamethoxazole) with concentrations between 170 and 300 ng/L for the different substances. The chosen pharmaceuticals were also detected in groundwater and surface water samples at the study site and used to qualify exchange/mixing of surface water and groundwater (BANZHAF et al., 2011). As some of the substances are known to exhibit redox-sensitive degradation, the redox-conditions were systematically varied throughout the experiment. This was realised by adding nitrate at the inflow of the column. During the experiment, which lasted for 2.5 months, four different nitrate concentrations (20-130 mg/L) were applied, beginning with the highest concentration. During the experiment water from the reservoir tank was sampled daily in order to detect a potential degradation of the pharmaceutical compounds before they enter the column. The effluent water was sampled every three hours to guarantee a maximum resolution for the analysis of the pharmaceuticals where necessary. In addition, major ions were analysed in the influent and effluent samples. Throughout the experiment physicochemical parameters (oxidation reduction potential (ORP), dissolved oxygen, electrical conductivity, and pH-value) were measured and logged at the outflow of the column

  3. Functional depletion of capsaicin-sensitive primary afferent fibers attenuates rat pain-related behaviors and paw edema induced by the venom of scorpion Buthus martensi Karch.

    PubMed

    Bai, Zhan-Tao; Liu, Tong; Pang, Xue-Yan; Jiang, Feng; Cheng, Ming; Ji, Yong-Hua

    2008-10-01

    The role of capsaicin-sensitive primary afferent fibers in rat pain-related behaviors and paw edema induced by scorpion Buthus martensi Karch (BmK) venom was investigated in this study. It was found that functional depletion of capsaicin-sensitive primary afferent fibers with a single systemic injection of resiniferatoxin (RTX) dramatically decreased spontaneous nociceptive behaviors, prevented the development of primary mechanical and thermal hyperalgesia as well as mirror-image mechanical hyperalgesia. RTX treatment significantly attenuated BmK venom-induced c-Fos expression in all laminaes of bilateral L4-L5 lumbar spinal cord, especially in superficial laminaes. Moreover, RTX treatment markedly reduced the early paw edema induced by BmK venom. Thus, the results indicate that capsaicin-sensitive primary afferent fibers play a critical role in various pain-related behaviors and paw edema induced by BmK venom in rats.

  4. Cut-Off Value for Pain Sensitivity Questionnaire in Predicting Surgical Success in Patients with Lumbar Disc Herniation

    PubMed Central

    Azimi, Parisa; Benzel, Edward C.

    2016-01-01

    Various factors related to predict surgical success were studied; however, a standard cut-off point for the Pain Sensitivity Questionnaire (PSQ) measure has not yet been established for a favorable surgical outcome for lumbar disc herniation (LDH). This study was to find the optimal cut-off point on the PSQ to distinguish surgical success in patients with LDH. A total of 154 patients with LDH consecutively referred to our clinic were enrolled into this prospective study between February 2011 and January 2014. All participants completed the PSQ. Patients completed the Oswestry Disability Index (ODI) score before surgery, and at 2 years after surgery. Surgical success was defined as a 13-point improvement from the baseline ODI scores. The cut-off value for PSQ was determined by the receiver-operating characteristic curve (ROC). The mean age of patients was 49.3±9.6 years, and there were 80 women. The mean time for follow-up assessment was 31±5 months (range 24–35). Post-surgical success was 79.9% (n = 123) at 2 years follow up. The mean score for the total PSQ, PSQ-minor, and PSQ-moderate were 6.0 (SD = 1.6), 5.4 (SD = 1.9) and 6.5 (SD = 1.7), respectively. Total PSQ score was also significantly correlated with the total scores of the ODI. The optimal total PSQ cut-off point was determined as > 5.2 to predict surgical success in LDH patients, with 80.0% sensitivity and 75.6% specificity (AUC-0.814, 95% CI 0.703–0.926). This study showed that the PSQ could be considered a parameter for predicting surgical success in patients with LDH, and can be useful in clinical practice. PMID:27494617

  5. Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization

    PubMed Central

    Romero, L; Zamanillo, D; Nadal, X; Sánchez-Arroyos, R; Rivera-Arconada, I; Dordal, A; Montero, A; Muro, A; Bura, A; Segalés, C; Laloya, M; Hernández, E; Portillo-Salido, E; Escriche, M; Codony, X; Encina, G; Burgueño, J; Merlos, M; Baeyens, JM; Giraldo, J; López-García, JA; Maldonado, R; Plata-Salamán, CR; Vela, JM

    2012-01-01

    BACKGROUND AND PURPOSE The sigma-1 (σ1) receptor is a ligand-regulated molecular chaperone that has been involved in pain, but there is limited understanding of the actions associated with its pharmacological modulation. Indeed, the selectivity and pharmacological properties of σ1 receptor ligands used as pharmacological tools are unclear and the demonstration that σ1 receptor antagonists have efficacy in reversing central sensitization-related pain sensitivity is still missing. EXPERIMENTAL APPROACH The pharmacological properties of a novel σ1 receptor antagonist (S1RA) were first characterized. S1RA was then used to investigate the effect of pharmacological antagonism of σ1 receptors on in vivo nociception in sensitizing conditions and on in vitro spinal cord sensitization in mice. Drug levels and autoradiographic, ex vivo binding for σ1 receptor occupancy were measured to substantiate behavioural data. KEY RESULTS Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of σ1 receptors in the CNS was significantly correlated with the antinociceptive effects. No pharmacodynamic tolerance to the antiallodynic and antihyperalgesic effect developed following repeated administration of S1RA to nerve-injured mice. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of σ1 receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. CONCLUSIONS AND IMPLICATIONS These findings contribute to evidence identifying the σ1 receptor as a modulator of activity-induced spinal sensitization and pain hypersensitivity, and suggest σ1 receptor antagonists as potential novel treatments for neuropathic pain. PMID:22404321

  6. Enhanced Laboratory Sensitivity to Variation of the Fine-Structure Constant using Highly Charged Ions

    SciTech Connect

    Berengut, J. C.; Dzuba, V. A.; Flambaum, V. V.

    2010-09-17

    We study atomic systems that are in the frequency range of optical atomic clocks and have enhanced sensitivity to potential time variation of the fine-structure constant {alpha}. The high sensitivity is due to coherent contributions from three factors: high nuclear charge Z, high ionization degree, and significant differences in the configuration composition of the states involved. Configuration crossing keeps the frequencies in the optical range despite the large ionization energies. We discuss a few promising examples that have the largest {alpha} sensitivities seen in atomic systems.

  7. Enhanced laboratory sensitivity to variation of the fine-structure constant using highly charged ions.

    PubMed

    Berengut, J C; Dzuba, V A; Flambaum, V V

    2010-09-17

    We study atomic systems that are in the frequency range of optical atomic clocks and have enhanced sensitivity to potential time variation of the fine-structure constant α. The high sensitivity is due to coherent contributions from three factors: high nuclear charge Z, high ionization degree, and significant differences in the configuration composition of the states involved. Configuration crossing keeps the frequencies in the optical range despite the large ionization energies. We discuss a few promising examples that have the largest α sensitivities seen in atomic systems.

  8. Sensitivity comparison of laboratory-cultured and field-collected amphipod Corophium multisetosum in toxicity tests.

    PubMed

    Menchaca, Iratxe; Belzunce, María Jesús; Franco, Javier; Garmendia, Joxe Mikel; Montero, Natalia; Revilla, Marta

    2010-04-01

    The feasibility of using lab-cultured amphipods Corophium multisetosum (Stock 1952) to evaluate the toxicity of contaminants present within marine sediments was studied. This was done by comparing the sensitivity of lab-cultured amphipods in a cadmium toxicity test and to toxic sediment samples, during a 10-days bioassay, with field collected individuals. Different responses were observed between field and cultured individuals. Cadmium test indicated high temporal variability in the LC(50) values of field amphipods (2.40-6.55 mg L(-1)). Sensitivity of cultured amphipods was within the seasonal range of the field individuals (5.81 mg L(-1), LC(50)). However, culture amphipods showed much lower sensitivity in toxic sediment samples. Our results indicate that sensitivity should be determined using a sediment matrix, if the assessment of toxicity is based upon bioassays performed with cultured burrower-amphipods.

  9. A Laboratory Exercise Illustrating the Sensitivity and Specificity of Western Blot Analysis

    ERIC Educational Resources Information Center

    Chang, Ming-Mei; Lovett, Janice

    2011-01-01

    Western blot analysis, commonly known as "Western blotting," is a standard tool in every laboratory where proteins are analyzed. It involves the separation of polypeptides in polyacrylamide gels followed by the electrophoretic transfer of the separated polypeptides onto a nitrocellulose or polyvinylidene fluoride membrane. A replica of the…

  10. Rapid, Sensitive, Enzyme-Immunodotting Assay for Detecting Cow Milk Adulteration in Sheep Milk: A Modern Laboratory Project

    NASA Astrophysics Data System (ADS)

    Inda, Luis A.; Razquín, Pedro; Lampreave, Fermín; Alava, María A.; Calvo, Miguel

    1998-12-01

    Specificity, sensitivity, and experimental simplicity make the immunoenzymatic assay suitable for a variety of laboratories dedicated to diverse activities such as research, quality control in food analysis, or clinical biochemistry. In these assays, the antibody that specifically recognizes the antigen is covalently attached to an enzyme. Once the antigen-antibody immunocomplex is formed, the enzymatic reaction gives a colored product that allows the detection of the initial antigen. The aim of this work was the design of a new laboratory project appropriate for use in courses of biochemistry, immunochemistry, or analytical chemistry. The assay described here detects the presence of cow milk in milk of other species. The main application is the detection of cow milk in sheep milk and cheese. Specific proteins, immunoglobulins (IgG) of the fraudulent bovine milk, are specifically recognized and retained by antibodies immobilized on a membrane. The binding of a second antibody covalently attached to horseradish peroxidase (HRP) allows the development of a visible signal. Thus, students can rapidly detect milk adulterations using a specific, sensitive, and safe experimental approach. The experiment allows students to apply their theoretical knowledge, resulting in a stimulating experience of solving a real problem during a 4-hour laboratory period.

  11. Sensitivity analysis of laboratory based mine overburden analytical techniques for the prediction of acidic mine drainage. Final report

    SciTech Connect

    Bradham, W.S.; Caruccio, F.T.

    1995-09-01

    A three part sensitivity analysis was conducted to evaluate commonly used mine overburden analytical techniques. The primary objectives of the study were: identify and evaluate the effects of variability in mine overburden geochemistry, as measured by pyrite weight percent and neutralization potential (NP), on variability of contaminant production; determine which acid/base accounting interpretation technique best predicts both qualitative and quantitative leachate quality in laboratory analytical testing; and identify the predominant factors of weathering cells, soxhlet extraction, and column leaching tests, and evaluate variability of contaminant production due to variations in; storage conditions, leachant temperature, particle size, particle sorting efficiency, and leaching interval.

  12. 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.

  13. Spatial resolution of the pain system: a proximal-to-distal gradient of sensitivity revealed with psychophysical testing.

    PubMed

    Weissman-Fogel, Irit; Brayer-Zwi, Nurit; Defrin, Ruth

    2012-01-01

    The spatial resolution of the pain system has not been studied in depth, and results are contradictory regarding the gradient of spatial resolution. Microneurographic recordings have revealed smaller receptive fields and higher density of nociceptors in more distal than proximal leg regions, whereas histological studies report higher density of C-fibers in more proximal than distal body regions. Due to this controversy, we conducted various psychophysical tests in order to examine the nociceptive spatial resolution and its gradient. Heat-pain threshold (HPT), perceived pain intensity, spatial summation (SS) of pain, two-point discrimination (2PD) of pain, and pain localization were measured in four body regions: upper back, thigh, lower leg, and foot. The highest HPT was demonstrated in the lower leg as compared with more proximal regions (P < 0.0001). SS was observed in all the regions and was found to be smallest in the foot (P < 0.05). The smallest 2PD and localization distances were found in the foot (P < 0.01) as compared with the lower leg and upper back. It appears that the nociceptive spatial resolution has a proximal-to-distal pattern of performance, namely that the spatial resolution of pain is finer in more distal than proximal body regions, similar to that of the touch system.

  14. Gray's reinforcement sensitivity model and child psychopathology: laboratory and questionnaire assessment of the BAS and BIS.

    PubMed

    Colder, Craig R; O'Connor, Roisin M

    2004-08-01

    The Behavioral Approach System (BAS) and Behavioral Inhibition System (BIS) are widely studied components of Gray's sensitivity to reinforcement model. There is growing interest in integrating the BAS and BIS into models of risk for psychopathology, however, few measures assess BAS and BIS functioning in children. We adapted a questionnaire measure and reaction time task from adult studies to assess the BAS and BIS in a sample of 9-12 year olds (N = 63; 42% female). A continuous performance task was also administered to assess physiological correlates of the BAS and BIS. Factor analysis supported 3 subdimensions of the BAS (Drive, Reward Responsivity, and Impulsivity/Fun seeking), and one dimension of the BIS (sensitivity to punishment). Results supported the utility of the questionnaire measures and reaction time task as assessments of BAS and BIS functioning. Moreover, these measures were associated with internalizing and externalizing problem behavior as expected. High levels of impulsivity/fun seeking, but not drive or reward responsivity, were associated with high levels of externalizing problems, whereas high levels of sensitivity to punishment were associated with high levels of internalizing behavior problems. The relation between physiological indices and caregiver reports of the BAS, BIS, and problem behavior were complex and not consistent with expectation.

  15. The Methanolic Extract from Murraya koenigii L. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+ Channel as Antinociceptive Mechanism

    PubMed Central

    Sharmin Ani, Nushrat; Chakraborty, Sudip

    2016-01-01

    Murraya koenigii L. is a perennial shrub, belonging to the family Rutaceae. Traditionally, the leaves of this plant are extensively used in treatment of a wide range of diseases and disorders including pain and inflammation. Although researchers have revealed the antinociceptive effects of this plant's leaves during past few years, the mechanisms underlying these effects are still unknown. Therefore, the present study evaluated some antinociceptive mechanisms of the methanolic extract of M. koenigii (MEMK) leaves along with its antinociceptive potential using several animal models. The antinociceptive effects of MEMK were evaluated using formalin-induced licking and acetic acid-induced writhing tests at the doses of 50, 100, and 200 mg/kg. In addition, we also justified the possible participations of glutamatergic system and ATP-sensitive potassium channels in the observed activities. Our results demonstrated that MEMK significantly (p < 0.01) inhibited the pain thresholds induced by formalin and acetic acid in a dose-dependent manner. MEMK also significantly (p < 0.01) suppressed glutamate-induced pain. Moreover, pretreatment with glibenclamide (an ATP-sensitive potassium channel blocker) at 10 mg/kg significantly (p < 0.05) reversed the MEMK-mediated antinociception. These revealed that MEMK might have the potential to interact with glutamatergic system and the ATP-sensitive potassium channels to exhibit its antinociceptive activities. Therefore, our results strongly support the antinociceptive effects of M. koenigii leaves and provide scientific basis of their analgesic uses in the traditional medicine. PMID:27812367

  16. [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.

  17. Effects of pesticides on soil invertebrates in laboratory studies: a review and analysis using species sensitivity distributions.

    PubMed

    Frampton, Geoff K; Jansch, Stephan; Scott-Fordsmand, Janeck J; Römbke, Jörg; Van den Brink, Paul J

    2006-09-01

    Species sensitivity distributions (SSD) and 5% hazardous concentrations (HC5) are distribution-based approaches for assessing environmental risks of pollutants. These methods have potential for application in pesticide risk assessments, but their applicability for assessing pesticide risks to soil invertebrate communities has not been evaluated. Using data obtained in a systematic review, the present study investigates the relevance of SSD and HC5 for predicting pesticide risks to soil invertebrates. Altogether, 1950 laboratory toxicity data were obtained, representing 250 pesticides and 67 invertebrate taxa. The majority (96%) of pesticides have toxicity data for fewer than five species. Based on a minimum of five species, the best available endpoint data (acute mortality median lethal concentration) enabled SSD and HC5 to be calculated for 11 pesticides (atrazine, carbendazim, chlorpyrifos, copper compounds, diazinon, dimethoate, gamma-hexachlorocyclohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and propoxur). Arthropods and oligochaetes exhibit pronounced differences in their sensitivity to most of these pesticides. The standard test earthworm species, Eisenia fetida sensu lato, is the species that is least sensitive to insecticides based on acute mortality, whereas the standard Collembola test species, Folsomia candida, is among the most sensitive species for a broad range of toxic modes of action (biocide, fungicide, herbicide, and insecticide). These findings suggest that soil arthropods should be tested routinely in regulatory risk assessments. In addition, the data indicate that the uncertainty factor for earthworm acute mortality tests (i.e., 10) does not fully cover the range of earthworm species sensitivities and that acute mortality tests would not provide the most sensitive risk estimate for earthworms in the majority (95%) of cases.

  18. Quality Assurance in the Polio Laboratory. Cell Sensitivity and Cell Authentication Assays.

    PubMed

    Dunn, Glynis

    2016-01-01

    The accuracy of poliovirus surveillance is largely dependent on the quality of the cell lines used for virus isolation, which is the foundation of poliovirus diagnostic work. Many cell lines are available for the isolation of enteroviruses, whilst genetically modified L20B cells can be used as a diagnostic tool for the identification of polioviruses. To be confident that cells can consistently isolate the virus of interest, it is necessary to have a quality assurance system in place, which will ensure that the cells in use are not contaminated with other cell lines or microorganisms and that they remain sensitive to the viruses being studied.The sensitivity of cell lines can be assessed by the regular testing of a virus standard of known titer in the cell lines used for virus isolation. The titers obtained are compared to previously obtained titers in the same assay, so that any loss of sensitivity can be detected.However, the detection of cell line cross contamination is more difficult. DNA bar coding is a technique that uses a short DNA sequence from a standardized position in the genome as a molecular diagnostic assay for species-level identification. For almost all groups of higher animals, the cytochrome c oxidase subunit 1 of mitochondrial DNA (CO1) is emerging as the standard barcode region. This region is 648 nucleotide base pairs long in most phylogenetic groups and is flanked by regions of conserved sequences, making it relatively easy to isolate and analyze. DNA barcodes vary among individuals of the same species to a very minor degree (generally less than 1-2 %), and a growing number of studies have shown that the COI sequences of even closely related species differ by several per cent, making it possible to identify different species with high confidence.

  19. Sandia National Laboratories Small-Scale Sensitivity Testing (SSST) Report: Calcium Nitrate Mixtures with Various Fuels.

    SciTech Connect

    Phillips, Jason Joe

    2014-07-01

    Based upon the presented sensitivity data for the examined calcium nitrate mixtures using sugar and sawdust, contact handling/mixing of these materials does not present hazards greater than those occurring during handling of dry PETN powder. The aluminized calcium nitrate mixtures present a known ESD fire hazard due to the fine aluminum powder fuel. These mixtures may yet present an ESD explosion hazard, though this has not been investigated at this time. The detonability of these mixtures will be investigated during Phase III testing.

  20. Sensitization of P2X3 receptors by cystathionine β-synthetase mediates persistent pain hypersensitivity in a rat model of lumbar disc herniation.

    PubMed

    Wang, Qianliang; Zhu, Hongyan; Zou, Kang; Yuan, Bo; Zhou, You-Lang; Jiang, Xinghong; Yan, Jun; Xu, Guang-Yin

    2015-03-20

    Lumbar disc herniation (LDH) is a major cause of discogenic low back pain and sciatica, but the underlying mechanisms remain largely unknown. Hydrogen sulfide (H2S) is becoming recognized for its involvement in a wide variety of processes including inflammation and nociception. The present study was designed to investigate the roles of the H2S signaling pathway in the regulation of expression and function of purinergic receptors (P2XRs) in dorsal root ganglion (DRG) neurons from rats with LDH. LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. Implantation of autologous NP induced persistent pain hypersensitivity, which was partially reversed by an intrathecal injection of A317491, a potent inhibitor of P2X3Rs and P2X2/3Rs. The NP induced persistent pain hypersensitivity was associated with the increased expression of P2X3Rs, but not P2X1Rs and P2X2Rs, receptors in L5-6 DRGs. NP implantation also produced a 2-fold increase in ATP-induced intracellular calcium signals in DRG neurons when compared to those of controls (P < 0.05). Interestingly, NP implantation significantly enhanced expression of the endogenous hydrogen sulfide producing enzyme, cystathionine-β-synthetase (CBS). Systematic administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, suppressed the upregulation of P2X3R expression and the potentiation of ATP-induced intracellular calcium signals in DRG neurons (P < 0.05). Intrathecal injection of AOAA markedly attenuated NP induced- persistent pain hypersensitivity. Our results suggest that sensitization of P2X3Rs, which is likely mediated by CBS-H2S signaling in primary sensory neurons, contributes to discogenic pain. Targeting CBS/H2S-P2X3R signaling may represent a potential treatment for neuropathic pain caused by LDH.

  1. A Validated High-Throughput Fluorometric Method for Determination of Omeprazole in Quality Control Laboratory via Charge Transfer Sensitized Fluorescence.

    PubMed

    Mahmoud, Ashraf M; Ahmed, Sameh A

    2016-03-01

    A high-throughput 96-microwell plate fluorometric method was developed and validated to determine omeprazole (OMZ) in its dosage forms. The method was based on the charge-transfer (CT) sensitized fluorescence reaction of OMZ with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ). This fluorescence reaction provided a new approach for simple, sensitive and selective determinations of OMZ in pharmaceutical preparations. In the present method, the fluorescence reaction was carried out in 96-microwell plates as reaction vessels in order to increase the automation of the methodology and the efficiency of its use in quality control laboratories. All factors affecting the fluorescence reaction were carefully studied and the conditions were optimized. The stoichiometry of the fluorescence reaction between OMZ and DDQ was determined and the reaction mechanism was suggested. Under the optimum conditions, the linear range was 100-6000 ng/ml with the lowest LOD of 33 ng/ml. Analytical performance of the proposed assay, in terms of accuracy and precision, was statistically validated and the results were satisfactory; RSD was <2.6 % and the accuracy was 98.6-101.6 %. The method was successfully applied to the analysis of OMZ in its dosage forms; the recovery values were 98.26-99.60 ± 0.95-2.22 %. The developed methodology may provide a safer, automated and economic tool for the analysis of OMZ in quality control laboratories.

  2. Intra-Articular Corticosteroids in Addition to Exercise for Reducing Pain Sensitivity in Knee Osteoarthritis: Exploratory Outcome from a Randomized Controlled Trial

    PubMed Central

    Soriano-Maldonado, Alberto; Klokker, Louise; Bartholdy, Cecilie; Bandak, Elisabeth; Ellegaard, Karen; Bliddal, Henning; Henriksen, Marius

    2016-01-01

    Objective To assess the effects of one intra-articular corticosteroid injection two weeks prior to an exercise-based intervention program for reducing pain sensitivity in patients with knee osteoarthritis (OA). Design Randomized, masked, parallel, placebo-controlled trial involving 100 participants with clinical and radiographic knee OA that were randomized to one intra-articular injection on the knee with either 1 ml of 40 mg/ml methylprednisolone (corticosteroid) dissolved in 4 ml lidocaine (10 mg/ml) or 1 ml isotonic saline (placebo) mixed with 4 ml lidocaine (10 mg/ml). Two weeks after the injections all participants undertook a 12-week supervised exercise program. Main outcomes were changes from baseline in pressure-pain sensitivity (pressure-pain threshold [PPT] and temporal summation [TS]) assessed using cuff pressure algometry on the calf. These were exploratory outcomes from a randomized controlled trial. Results A total of 100 patients were randomized to receive either corticosteroid (n = 50) or placebo (n = 50); 45 and 44, respectively, completed the trial. Four participants had missing values for PPT and one for TS at baseline; thus modified intention-to-treat populations were analyzed. The mean group difference in changes from baseline at week 14 was 0.6 kPa (95% CI: -1.7 to 2.8; P = 0.626) for PPT and 384 mm×sec (95% CI: -2980 to 3750; P = 0.821) for TS. Conclusions These results suggest that adding intra-articular corticosteroid injection 2 weeks prior to an exercise program does not provide additional benefits compared to placebo in reducing pain sensitivity in patients with knee OA. Trial Registration EU clinical trials (EudraCT): 2012-002607-18 PMID:26871954

  3. Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat

    PubMed Central

    Sagar, D.R.; Nwosu, L.; Walsh, D.A.; Chapman, V.

    2015-01-01

    Summary Objective Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. Design In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. Results MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P < 0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. Conclusion The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. PMID:25623624

  4. Serotonin facilitates peripheral pain sensitivity in a manner that depends on the nonproton ligand sensing domain of ASIC3 channel.

    PubMed

    Wang, Xiang; Li, Wei-Guang; Yu, Ye; Xiao, Xian; Cheng, Jin; Zeng, Wei-Zheng; Peng, Zhong; Xi Zhu, Michael; Xu, Tian-Le

    2013-03-06

    Tissue acidosis and inflammatory mediators play critical roles in inflammatory pain. Extracellular acidosis activates acid-sensing ion channels (ASICs), which have emerged as key sensors for extracellular protons in the central and peripheral nervous systems and play key roles in pain sensation and transmission. Additionally, inflammatory mediators, such as serotonin (5-HT), are known to enhance pain sensation. However, functional interactions among protons, inflammatory mediators, and ASICs in pain sensation are poorly understood. In the present study, we show that 5-HT, a classical pro-inflammatory mediator, specifically enhances the proton-evoked sustained, but not transient, currents mediated by homomeric ASIC3 channels and heteromeric ASIC3/1a and ASIC3/1b channels. Unexpectedly, the effect of 5-HT on ASIC3 channels does not involve activation of 5-HT receptors, but is mediated via a functional interaction between 5-HT and ASIC3 channels. We further show that the effect of 5-HT on ASIC3 channels depends on the newly identified nonproton ligand sensing domain. Finally, coapplication of 5-HT and acid significantly increased pain-related behaviors as assayed by the paw-licking test in mice, which was largely attenuated in ASIC3 knock-out mice, and inhibited by the nonselective ASIC inhibitor amiloride. Together, these data identify ASIC3 channels as an unexpected molecular target for acute actions of 5-HT in inflammatory pain sensation and reveal an important role of ASIC3 channels in regulating inflammatory pain via coincident detection of extracellular protons and inflammatory mediators.

  5. Development of a sensitive assay for the detection of Pseudoloma neurophilia in laboratory populations of the zebrafish Danio rerio

    PubMed Central

    Sanders, Justin L; Kent, Michael L

    2012-01-01

    Zebrafish (Danio rerio) are an increasingly important biological model in many areas of research. Diseases of zebrafish, especially those resulting in chronic, sub lethal infections, are of great concern due to the potential for non-protocol induced variation. The microsporidium, Pseudoloma neurophilia, is a common parasite of laboratory zebrafish. Current methods for detection of this parasite require lethal sampling of fish, which is often undesirable with poorly spawning mutant lines and small populations. We present here an improved molecular based diagnostic assay using real-time PCR, and including sonication treatment prior to DNA extraction. Sensitivity was increased compared to the previously published conventional PCR-based assay based on a dilution experiment, showing that this new assay had the ability to detect parasite DNA in one log higher dilution than the conventional PCR-based assay, which did not include sonication. Comparisons of several DNA extraction methods were also performed to determine the method providing the maximum sensitivity. Sonication was found to be the most effective method for disrupting spores. Further, we demonstrate the application of this method for testing of water, eggs and sperm, providing a potential non-lethal method for detection of this parasite in zebrafish colonies with a sensitivity of 10 spores per liter, 2 spores per egg and 10 spores per μl of sperm, respectively. PMID:22013754

  6. Chronic toxicity of copper to five benthic invertebrates in laboratory-formulated sediment: sensitivity comparison and preliminary risk assessment.

    PubMed

    Roman, Yblin E; De Schamphelaere, Karel A C; Nguyen, Lien T H; Janssen, Colin R

    2007-11-15

    Five benthic organisms commonly used for sediment toxicity testing were chronically (28 to 35 days) exposed to copper in standard laboratory-formulated sediment (following Organization for Economic Cooperation and Development guidelines) and lethal and sub-lethal toxicities were evaluated. Sub-lethal endpoints considered were reproduction and biomass production for Lumbriculus variegatus, growth and reproduction for Tubifex tubifex, growth and emergence for Chironomus riparius, and growth for Gammarus pulex and Hyalella azteca. Expressed on whole-sediment basis the observed lethal sensitivity ranking (from most to least sensitive) was: G. pulex>L. variegatus>H. azteca=C. riparius=T. tubifex, with median chronic lethal concentrations (LC50) between 151 and 327 mg/kg dry wt. The sub-lethal sensitivity ranking (from most to least sensitive, with the most sensitive endpoint between parentheses): C. riparius (emergence)>T. tubifex (reproduction)=L. variegatus (reproduction)>G. pulex (growth)>H. azteca (growth), with median effective concentrations (EC50) between 59.2 and 194 mg/kg dry wt. No observed effect concentrations (NOEC) or 10% effective concentrations (EC10) for the five benthic invertebrates were used to perform a preliminary risk assessment for copper in freshwater sediment by means of (a) the "assessment factor approach" or (b) the statistical extrapolation approach (species sensitivity distribution). Depending on the data (NOEC or EC10) and the methodology used, we calculated a Predicted No Effect Concentration (PNEC) for sediment between 3.3 and 47.1 mg Cu/dry wt. This range is similar to the range of natural (geochemical) background concentrations of copper in sediments in Europe, i.e. 90% of sediments have a concentration between 5 and 49 mg Cu/kg dry wt. A detailed analysis of the outcome of this preliminary exercise highlighted that multiple issues need to be explored for achieving a scientifically more sound risk assessment and for the development of

  7. Quality assurance growing pains: a state perspective on implementing an organizational-wide quality system in environmental laboratories.

    PubMed

    Siders, S D

    1999-01-01

    To implement an effective and efficient quality system in a network of established environmental testing laboratories requires a committed long-term effort that is potentially fraught with multiple obstacles. This presentation discusses one state's ongoing efforts at implementing such a system. First is the need to convince management of the rationale for a quality systems-based approach versus the traditional QA/QC program. Once development of a quality system has been sanctioned, a team-based approach utilizing project planning tools is a good way to approach the effort. Resources are assigned to the development of key quality system components, and generally a phased-deployment or roll-out works best. Once implementation is underway, assuring operational utilization and compliance with the quality system are vital steps in the process. Important to successful implementation is ongoing assessment and refinement of the quality system. Fundamental and key elements of the laboratory quality system are numerous and need to work in concert with each other. Quality system elements to be discussed in the presentation range from management and QA roles and functions to the typical documentation of laboratory policies and procedures. Numerous QA assessment tools and other vital quality system practices that play an important role in making a complete quality system are addressed. In addition, efforts must be undertaken to integrate the laboratory quality system with other management systems within the organization. The bottom line is that all environmental laboratories need a quality system more now than ever. Data users need it. Customers' expectations for data quality are high. USEPA policy and/or programs call for it. Additionally, good quality systems can benefit the organization in multiple ways and help avoid the "pay-me-now or pay-me-later" syndrome. In conclusion, all environmental testing laboratories (i.e., academic, private, commercial and especially

  8. Bilateral central pain sensitization in rats following a unilateral thalamic lesion may be treated with high doses of ketamine

    PubMed Central

    2013-01-01

    Background Central post-stroke pain is a neuropathic pain condition caused by a vascular lesion, of either ischemic or hemorrhagic origin, in the central nervous system and more precisely involving the spinothalamocortical pathway responsible for the transmission of painful sensations. Few animal models have been developed to study this problem. The objectives of this study were to evaluate different modalities of pain in a central neuropathic pain rat model and to assess the effects of ketamine administered at different doses. Animals were evaluated on the rotarod, Hargreaves, Von Frey and acetone tests. A very small hemorrhage was created by injecting a collagenase solution in the right ventral posterolateral thalamic nucleus. Following the establishment of the neuropathy, ketamine was evaluated as a therapeutic drug for this condition. Results Histopathological observations showed a well localized lesion with neuronal necrosis and astrocytosis following the collagenase injection that was localized within the VPL. No significant change in motor coordination was observed following surgery in either the saline or collagensae groups. In the collagenase group, a significant decrease in mechanical allodynia threshold was observed. A sporadic and transient cold allodynia was also noted. No thermal hyperalgesia was seen following the collagenase injection. Ketamine was then tested as a potential therapeutic drug. A significant decrease in motor coordination was seen only following the administration of 25 mg/kg of ketamine in both groups. An alleviation of mechanical allodynia was achieved only with the high ketamine dose. The minimal effective ketamine serum concentration (150 ng/mL) was only achieved in animals that received 25 mg/kg. Conclusions An intrathalamic hemorrhage induced a bilateral mechanical allodynia in rats. Cold hyperalgesia was observed in 60% of these animals. Mechanical allodynia was alleviated with high doses of ketamine which corresponded

  9. Effects of affective pictures on pain sensitivity and cortical responses induced by laser stimuli in healthy subjects and migraine patients.

    PubMed

    de Tommaso, Marina; Calabrese, Rita; Vecchio, Eleonora; De Vito Francesco, Vito; Lancioni, Giulio; Livrea, Paolo

    2009-11-01

    Visually induced analgesia has been correlated with the affective content of pleasant, neutral or unpleasant pictures. The aim of the present study was to assess the effect of affective images vision on laser evoked potentials and pain perception, in a cohort of healthy subjects and migraine patients. Twenty-two healthy subjects and 24 migraine without aura patients (recorded during the inter-critical phase) participated in the study. Eighty-four colour slides, arranged in two blocks, each consisting of 14 pleasant, 14 unpleasant and 14 neutral images, in random presentation, were chosen from the International Affective Picture System. The CO(2) laser stimuli were delivered on the dorsum of the right hand and supra-orbital zone at 7.5-watt intensity and 25-ms duration, in basal condition and during the viewing of affective pictures. Migraine patients expressed higher scores of valence and arousal for pleasant and unpleasant pictures, compared to controls. In both groups, a late positive potential in the 400-700 ms time range was clear for pleasant and unpleasant pictures, but its amplitude was significantly reduced in migraine patients. The pain rating and the N2 component were reduced in both groups during the visual task compared to basal condition. In migraineurs and controls the P2 wave was reduced during the vision of pleasant pictures, compared to basal condition. This indicates that stimulation by images with different affective content reduces subjective pain for a cognitive mechanism of attentive engagement, while a special inhibition of later LEPs is produced by a positive emotional impact. In migraine, affective images are able to modulate pain perception and LEPs, differently from other modalities of distraction, suggesting a possible emotive elaboration of painful stimuli.

  10. Roles of capsaicin-sensitive primary afferents in differential rat models of inflammatory pain: a systematic comparative study in conscious rats.

    PubMed

    Chen, Hui-Sheng; He, Xiang; Wang, Yang; Wen, Wei-Wei; You, Hao-Jun; Arendt-Nielsen, Lars

    2007-03-01

    To characterize the role of capsaicin-sensitive primary afferents in inflammatory pain, the effects of subcutaneous (s.c.) injection of 0.15% capsaicin on different chemical irritants-induced pathological nociception including persistent spontaneous nociception, primary thermal and mechanical hyperalgesia, and inflammatory response were systematically investigated in unanesthetized conscious rats. Four different animal models of inflammatory pain: the bee venom (BV) test, the formalin test, the carrageenan model, and the complete Freund's adjuvant (CFA) model, were employed and compared. Local pre-treatment with capsaicin produced a significant inhibition on the s.c. BV and formalin induced long-lasting persistent spontaneous nociception. However, this capsaicin-induced inhibitory effect on spontaneous nociception in the BV test was only found within the late phase (tonic nociception; 11-60 min), but not the early phase (acute nociception; 0-10 min). A complete preventing effect of capsaicin on the decreased thermal paw withdrawal latency was found in the BV, carrageenan, and CFA models. Nevertheless, pre-treatment with capsaicin only produced complete blocking effects on the decreased mechanical paw withdrawal threshold in the BV and carrageenan models, but not in the CFA model. For inflammatory response, a significant inhibition of the BV-elicited paw swelling was found following capsaicin treatment. In marked contrast, capsaicin did not produce any effects on the paw inflammation during exposure to carrageenan, CFA, and formalin. These data suggest that capsaicin-sensitive primary afferents may play differential roles in the induction and development of pathological nociception in differential inflammatory pain models. In contrast to other chemical irritants, BV-induced long-term spontaneous nociception, facilitated nociceptive behavior, and inflammation are modulated by peripheral capsaicin-sensitive afferents.

  11. The sensitivity of new laboratory-based heterogeneous freezing schemes for dust and biological particles to time and temperature

    NASA Astrophysics Data System (ADS)

    Niedermeier, D.; Ervens, B.; Hartmann, S.; Wex, H.; Stratmann, F.

    2012-12-01

    Heterogeneous ice nucleation has been recently described by means of the Soccer ball model that takes into account multiple nucleation sites on individual particles [Niedermeier et al., 2011]. In order to study sensitivities of the implied contact angle distributions, a modified version of the Soccer ball model is implemented into a parcel model that describes in detail heterogeneous ice formation and ice /liquid water partitioning [Ervens and Feingold, 2012]. Soccer ball model parameters (number of surface sites, mean and width of the contact angle distribution) are determined from immersion freezing measurements of mineral dust particles and bacteria performed with the Leipzig Aerosol Cloud Interaction Simulator [LACIS, Hartmann et al., 2011]. While biological particles (e.g., bacteria) are much less frequent in the atmosphere, they can induce droplet freezing already at about -5°C as opposed to dust that shows efficient freezing only at lower temperatures (below -15°C). We will identify updraft regimes, temperature and IN concentration ranges where dust or biological particles, respectively, might dominate the number concentration of frozen droplets in mixed phase clouds. Additional model studies will focus on the importance of time versus temperature dependence and explore the usefulness of alternative descriptions of the freezing behavior that can be derived based on the respective laboratory studies using LACIS. These descriptions include the choice of a single contact angle as opposed to contact angle distributions or time-independent expressions. These results reveal that under selected conditions, it might be a satisfactory approximation to assume singular freezing behavior. Our sensitivity studies will help to refine time-independent freezing parameterizations using laboratory data and help bridging the current divergence between deterministic approaches [e.g., Hoose and Möhler, 2012] and physically-based approaches (classical nucleation theory) that

  12. Pain management in neonates.

    PubMed

    Carbajal, Ricardo; Gall, Olivier; Annequin, Daniel

    2004-05-01

    Multiple lines of evidence suggest an increased sensitivity to pain in neonates. Repeated and prolonged pain exposure may affect the subsequent development of pain systems, as well as potentially contribute to alterations in long-term development and behavior. Despite impressive gains in the knowledge of neonatal pain mechanisms and strategies to treat neonatal pain acquired during the last 15 years, a large gap still exists between routine clinical practice and research results. Accurate assessment of pain is crucial for effective pain management in neonates. Neonatal pain management should rely on current scientific evidence more than the attitudes and beliefs of care-givers. Parents should be informed of pain relief strategies and their participation in the health care plan to alleviate pain should be encouraged. The need for systemic analgesia for both moderate and severe pain, in conjunction with behavioral/environmental approaches to pain management, is emphasized. A main sources of pain in the neonate is procedural pain which should always be prevented and treated. Nonpharmacological approaches constitute important treatment options for managing procedural pain. Nonpharmacological interventions (environmental and preventive measures, non-nutritive sucking, sweet solutions, skin-skin contact, and breastfeeding analgesia) can reduce neonatal pain indirectly by reducing the total amount of noxious stimuli to which infants are exposed, and directly, by blocking nociceptive transduction or transmission or by activation of descending inhibitory pathways or by activating attention and arousal systems that modulate pain. Opioids are the mainstay of pharmacological pain treatment but there are other useful medications and techniques that may be used for pain relief. National guidelines are necessary to improve neonatal pain management at the institutional level, individual neonatal intensive care units need to develop specific practice guidelines regarding pain

  13. Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone.

    PubMed

    Janal, M N; Colt, E W; Clark, W C; Glusman, M

    1984-05-01

    The effects of intense exercise on pain perception, mood, and plasma endocrine levels in man were studied under naloxone and saline conditions. Twelve long-distance runners (mean weekly mileage = 41.5) were evaluated on thermal, ischemic, and cold pressor pain tests and on mood visual analogue scales (VAS). Blood was drawn for determination of plasma levels of beta-endorphin-like immunoreactivity (BEir), growth hormone (GH), adrenocorticotrophic hormone (ACTH), and prolactin (PRL). These procedures were undertaken before and after a 6.3 mile run at 85% of maximal aerobic capacity. Subjects participated on two occasions in a double-blind procedure counterbalanced for drug order: on one day they received 2 i.v. injections of naloxone (0.8 mg in 2 ml vehicle each) at 20 min intervals following the run; on the other day, 2 equal volume injections of normal saline (2 ml). Sensory decision theory analysis of the responses to thermal stimulation showed that discriminability, P(A), was significantly reduced post-run under the saline condition, a hypoalgesic effect; response bias, B, was unaffected. Ischemic pain reports were significantly reduced post-run on the saline day, also a hypoalgesic effect. Naloxone reversed the post-run ischemic but not thermal hypoalgesic effects. Joy, euphoria, cooperation, and conscientiousness VAS ratings were elevated post-run; naloxone attenuated the elevation of joy and euphoria ratings only. Plasma levels of BEir, ACTH, GH, and PRL were significantly increased post-run. The results show that long-distance running produces hypoalgesia and mood elevation in man. The effects of naloxone implicate endogenous opioid neural systems as mechanisms of some but not all of the run-induced alterations in mood and pain perception.

  14. Neonatal pain

    PubMed Central

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  15. Neonatal pain.

    PubMed

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback.

  16. Dynamic pain phenotypes are associated with spinal cord stimulation-induced reduction in pain: A repeated measures observational pilot study

    PubMed Central

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

    2015-01-01

    Objective 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. Methods The current study evaluated clinical, psychological and laboratory pain measures at baseline, during trial SCS lead placement, as well as one month and three 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 three months post SCS implantation. Results Results suggest few changes in QST over time. However, central sensitization and CPM at baseline were significantly associated with clinical pain at three 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 three months following SCS implantation. Conclusions 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. PMID:25800088

  17. Pain Management in Horses.

    PubMed

    Guedes, Alonso

    2017-04-01

    There has been great progress in the understanding of basic neurobiologic mechanisms of pain, but this body of knowledge has not yet translated into new and improved analgesics. Progress has been made regarding pain assessment in horses, but more work is needed until sensitive and accurate pain assessment tools are available for use in clinical practice. This review summarizes and updates the knowledge concerning the cornerstones of pain medicine (understand, assess, prevent, and treat). It highlights the importance of understanding pain mechanisms and expressions to enable a rational approach to pain assessment, prevention, and management in the equine patient.

  18. Altered cytokine profile, pain sensitivity, and stress responsivity in mice with co-disruption of the developmental genes Neuregulin-1×DISC1.

    PubMed

    Desbonnet, Lieve; Cox, Rachel; Tighe, Orna; Lai, Donna; Harvey, Richard P; Waddington, John L; O'Tuathaigh, Colm M P

    2017-03-01

    The complex genetic origins of many human disorders suggest that epistatic (gene×gene) interactions may contribute to a significant proportion of their heritability estimates and phenotypic heterogeneity. Simultaneous disruption of the developmental genes and schizophrenia risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) in mice has been shown to produce disease-relevant and domain-specific phenotypic profiles different from that observed following disruption of either gene alone. In the current study, anxiety and stress responsivity phenotypes in male and female mutant mice with simultaneous disruption of DISC1 and NRG1 were examined. NRG1×DISC1 mutant mice were generated and adult mice from each genotype were assessed for pain sensitivity (hot plate and tail flick tests), anxiety (light-dark box), and stress-induced hypothermia. Serum samples were assayed to measure circulating levels of pro-inflammatory cytokines. Mice with the NRG1 mutation, irrespective of DISC1 mutation, spent significantly more time in the light chamber, displayed increased core body temperature following acute stress, and decreased pain sensitivity. Basal serum levels of cytokines IL8, IL1β and IL10 were decreased in NRG1 mutants. Mutation of DISC1, in the absence of epistatic interaction with NRG1, was associated with increased serum levels of IL1β. Epistatic effects were evident for IL6, IL12 and TNFα. NRG1 mutation alters stress and pain responsivity, anxiety, and is associated with changes in basal cytokine levels. Epistasis resulting from synergistic NRG1 and DISC1 gene mutations altered pro-inflammatory cytokine levels relative to the effects of each of these genes individually, highlighting the importance of epistatic mechanisms in immune-related pathology.

  19. Neurocognitive performance and physical function do not change with physical-cognitive-mindfulness training in female laboratory technicians with chronic musculoskeletal pain

    PubMed Central

    Jay, Kenneth; Brandt, Mikkel; Schraefel, mc; Jakobsen, Markus Due; Sundstrup, Emil; Sjøgaard, Gisela; Vinstrup, Jonas; Andersen, Lars L.

    2016-01-01

    Abstract Background: Cognitive and physical performance can be negatively affected by chronic pain. This study evaluates the effect of combined physical-, cognitive-, and mindfulness training (PCMT) on cognitive and physical performance. Methods: From a large pharmaceutical company in Denmark we randomly allocated 112 female laboratory technicians with chronic upper limb pain to group-based PCMT at the worksite or a reference group for 10 weeks. Neurocognitive performance was measured by the computerized central nervous system vital signs neurocognitive assessment battery. Physical function was assessed in terms of shoulder external rotation strength and rate of force development in a custom-made dynamometer setup. Results: No between-group differences (least square means [95% confidence interval]) from baseline to follow-up could be detected in any of the neurocognitive domains as measured by the central nervous system vital signs neurocognitive assessment battery, for example, Psychomotoer Speed 1.9 (−1.0 to 4.7), Reaction Time −4.0 (−19.5 to 11.6), Complex Attention −0.3 (−1.9 to 1.4), and Executive Function −0.2 (−3.5 to 3.0). Similarly, we found no change in maximal voluntary isometric strength −0.63 (−4.8 to 3.6), or rate of force development 14.8 (−12.6 to 42.2) of the shoulder external rotators. Finally, test–retest reliability of maximal voluntary contraction and rate of force development shoulder external rotation showed high reliability at 0 to 30 ms, 0 to 50 ms, 0 to 100 ms, and 0 to 200 ms with ICCs at 0.95, 0.92, 0.93, 0.92, and 0.91, respectively. Conclusion: Ten weeks of PCMT did not improve neurocognitive or physical performance. PMID:27977585

  20. Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen Blunts Evaluation Sensitivity to Both Negative and Positive Stimuli.

    PubMed

    Durso, Geoffrey R O; Luttrell, Andrew; Way, Baldwin M

    2015-06-01

    Acetaminophen, an effective and popular over-the-counter pain reliever (e.g., the active ingredient in Tylenol), has recently been shown to blunt individuals' reactivity to a range of negative stimuli in addition to physical pain. Because accumulating research has shown that individuals' reactivity to both negative and positive stimuli can be influenced by a single factor (an idea known as differential susceptibility), we conducted two experiments testing whether acetaminophen blunted individuals' evaluations of and emotional reactions to both negative and positive images from the International Affective Picture System. Participants who took acetaminophen evaluated unpleasant stimuli less negatively and pleasant stimuli less positively, compared with participants who took a placebo. Participants in the acetaminophen condition also rated both negative and positive stimuli as less emotionally arousing than did participants in the placebo condition (Studies 1 and 2), whereas nonevaluative ratings (extent of color saturation in each image; Study 2) were not affected by drug condition. These findings suggest that acetaminophen has a general blunting effect on individuals' evaluative and emotional processing, irrespective of negative or positive valence.

  1. Sensitization of lamina I spinoparabrachial neurons parallels heat hyperalgesia in the chronic constriction injury model of neuropathic pain

    PubMed Central

    Andrew, David

    2009-01-01

    It has been proposed that spinal lamina I neurons with ascending axons that project to the midbrain play a crucial role in hyperalgesia. To test this hypothesis the quantitative properties of lamina I spinoparabrachial neurons in the chronic constriction injury (CCI) model of neuropathic pain were compared to those of unoperated and sham-operated controls. Behavioural testing showed that animals with a CCI exhibited heat hyperalgesia within 4 days of the injury, and this hyperalgesia persisted throughout the 14-day post-operative testing period. In the CCI, nociceptive lamina I spinoparabrachial neurons had heat thresholds that were significantly lower than controls (43.0 ± 2.8°C vs. 46.7 ± 2.6°C; P < 10−4, ANOVA). Nociceptive lamina I spinoparabrachial neurons were also significantly more responsive to graded heat stimuli in the CCI, compared to controls (P < 0.02, 2-factor repeated-measures ANOVA), and increased after-discharges were also observed. Furthermore, the heat-evoked stimulus–response functions of lamina I spinoparabrachial neurons in CCI animals co-varied significantly (P < 0.03, ANCOVA) with the amplitude of heat hyperalgesia determined behaviourally. Taken together these results are consistent with the hypothesis that lamina I spinoparabrachial neurons have an important mechanistic role in the pathophysiology of neuropathic pain. PMID:19289544

  2. 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

  3. Sacroiliac joint pain.

    PubMed

    Dreyfuss, Paul; Dreyer, Susan J; Cole, Andrew; Mayo, Keith

    2004-01-01

    The sacroiliac joint is a source of pain in the lower back and buttocks in approximately 15% of the population. Diagnosing sacroiliac joint-mediated pain is difficult because the presenting complaints are similar to those of other causes of back pain. Patients with sacroiliac joint-mediated pain rarely report pain above L5; most localize their pain to the area around the posterior superior iliac spine. Radiographic and laboratory tests primarily help exclude other sources of low back pain. Magnetic resonance imaging, computed tomography, and bone scans of the sacroiliac joint cannot reliably determine whether the joint is the source of the pain. Controlled analgesic injections of the sacroiliac joint are the most important tool in the diagnosis. Treatment modalities include medications, physical therapy, bracing, manual therapy, injections, radiofrequency denervation, and arthrodesis; however, no published prospective data compare the efficacy of these modalities.

  4. Neurofibromatosis and the Painful Neuroma

    DTIC Science & Technology

    2010-01-01

    clinical treatment of neuropathic pain and pain from neuroma formation. Systemic administration of lidocaine has also been used to treat neuropathic... pain . We performed an experiment to compare the effect of pregabalin(PGB), morphine, and lidocaine (LDC) on the TNT model. Method: TNT model...of mechanical hyperalgesia (partially dennervated skin). Further, systemic lidocaine can be expected to impact neuroma sensitivity related pain

  5. 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.

  6. Groin pain

    MedlinePlus

    Pain - groin; Lower abdominal pain; Genital pain; Perineal pain ... Common causes of groin pain include: Pulled muscle, tendon, or ligaments in the leg: This problem often occurs in people who play sports such as ...

  7. The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization.

    PubMed

    Gazerani, Parisa; Staahl, Camilla; Drewes, Asbjøn M; Arendt-Nielsen, Lars

    2006-06-01

    The trigeminovascular system is involved in migraine. Efficacy of Botulinum Toxin type A (BoNT-A) in migraine has been investigated in clinical studies but the mechanism of action remains unexplored. It is hypothesized that BoNT-A inhibits peripheral sensitization of nociceptive fibers and indirectly reduces central sensitization. We examined the effect of intramuscular injection of BoNT-A on an experimental human model of trigeminal sensitization induced by intradermal capsaicin injection to the forehead. BoNT-A (BOTOX) or saline was injected intramuscularly in precranial, neck and shoulder muscles to 32 healthy male volunteers in a double blind-randomized manner. Intradermally capsaicin-induced pain, flare and secondary hyperalgesia were obtained before and 1, 4 and 8 weeks after the above treatments. A significant suppressive effect of BoNT-A on pain, flare and hyperalgesia area was observed. The pain intensity area was significantly smaller in BoNT-A group (9.16+/-0.83 cm x s) compared to saline group (15.41+/-0.83cm x s) (P=0.011). The flare area was also reduced significantly in BoNT-A group (29.81+/-0.69 cm2) compared to saline group (39.71+/-0.69 cm2) (P<0.001). Similarly, the mean area of secondary hyperalgesia was significantly smaller in BoNT-A group (4.25+/-0.91 cm2) compared to saline group (7.03+/-0.91 cm2) (P=0.040). Post hoc analysis showed significant differences across the trials with a remarkable suppression effect of BoNT-A on capsaicin-induced sensory and vasomotor reactions as early as week1 (P<0.001). BoNT-A presented suppressive effects on the trigeminal/cervical nociceptive system activated by intradermal injection of capsaicin to the forehead. The effects are suggested to be caused by a local peripheral effect of BoNT-A on cutaneous nociceptors.

  8. Early Painful Diabetic Neuropathy Is Associated with Differential Changes in Tetrodotoxin-sensitive and -resistant Sodium Channels in Dorsal Root Ganglion Neurons in the Rat*

    PubMed Central

    Hong, Shuangsong; Morrow, Thomas J.; Paulson, Pamela E.; Isom, Lori L.; Wiley, John W.

    2007-01-01

    Diabetic neuropathy is a common form of peripheral neuropathy, yet the mechanisms responsible for pain in this disease are poorly understood. Alterations in the expression and function of voltage-gated tetrodotoxin-resistant (TTX-R) sodium channels have been implicated in animal models of neuropathic pain, including models of diabetic neuropathy. We investigated the expression and function of TTX-sensitive (TTX-S) and TTX-R sodium channels in dorsal root ganglion (DRG) neurons and the responses to thermal hyperalgesia and mechanical allodynia in streptozotocin-treated rats between 4–8 weeks after onset of diabetes. Diabetic rats demonstrated a significant reduction in the threshold for escape from innocuous mechanical pressure (allodynia) and a reduction in the latency to withdrawal from a noxious thermal stimulus (hyperalgesia). Both TTX-S and TTX-R sodium currents increased significantly in small DRG neurons isolated from diabetic rats. The voltage-dependent activation and steady-state inactivation curves for these currents were shifted negatively. TTX-S currents induced by fast or slow voltage ramps increased markedly in neurons from diabetic rats. Immunoblots and immunofluorescence staining demonstrated significant increases in the expression of Nav1.3 (TTX-S) and Nav1.7 (TTX-S) and decreases in the expression of Nav1.6 (TTX-S) and Nav1.8 (TTX-R) in diabetic rats. The level of serine/threonine phosphorylation of Nav1.6 and Nav1.8 increased in response to diabetes. In addition, increased tyrosine phosphorylation of Nav1.6 and Nav1.7 was observed in DRGs from diabetic rats. These results suggest that both TTX-S and TTX-R sodium channels play important roles and that differential phosphorylation of sodium channels involving both serine/threonine and tyrosine sites contributes to painful diabetic neuropathy. PMID:15123645

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

    PubMed

    Goodin, Burel R; Bulls, Hailey W

    2013-05-01

    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 studied adequately, 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.

  10. In Vivo Luminescent Imaging of NF-κB Activity and NF-κB Related Serum Cytokine Levels Predict Pain Sensitivities in a Rodent Model Of Peripheral Neuropathy

    PubMed Central

    Bowles, Robby D.; Karikari, Isaac O.; VanDerwerken, Douglas N.; Sinclair, Michael S.; Bell, Richard D.; Riebe, Kristina J.; Huebner, Janet L.; Kraus, Virginia B.; Sempowski, Gregory D.; Setton, Lori A.

    2016-01-01

    Background Methods for the detection of the temporal and spatial generation of painful symptoms are needed to improve the diagnosis and treatment of painful neuropathies and to aid preclinical screening of molecular therapeutics. Methods In this study, we utilized in vivo luminescent imaging of NF-κB activity and serum cytokine measures to investigate relationships between the NF-κB regulatory network and the presentation of painful symptoms in a model of neuropathy. Results The chronic constriction injury model led to temporal increases in NF-κB activity that were strongly and non-linearly correlated with the presentation of pain sensitivities (i.e. mechanical allodynia and thermal hyperalgesia). The delivery of NEMO-binding domain peptide reduced pain sensitivities through the inhibition of NF-κB activity in a manner consistent with the demonstrated non-linear relationship. Importantly, the combination of non-invasive measures of NF-κB activity and NF-κB regulated serum cytokines produced a highly predictive model of both mechanical (R2=0.86) and thermal (R2=0.76) pain centered on the NF-κB regulatory network (NF-κB, IL-6, CXCL1). Conclusions Using in vivo luminescent imaging of NF-κB activity and serum cytokine measures, this work establishes NF-κB and NF-κB regulated cytokines as novel multivariate biomarkers of pain-related sensitivity in this model of neuropathy that may be useful for the rapid screening of novel molecular therapeutics. PMID:26032161

  11. Chronic Pain

    MedlinePlus

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on for ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis Pain ...

  12. Abdominal pain

    MedlinePlus

    Stomach pain; Pain - abdomen; Belly ache; Abdominal cramps; Bellyache; Stomachache ... Almost everyone has pain in the abdomen at some point. Most of the time, it is not serious. How bad your pain is ...

  13. Flank pain

    MedlinePlus

    Pain - side; Side pain ... Flank pain can be a sign of a kidney problem. But, since many organs are in this area, other causes are possible. If you have flank pain and fever , chills, blood in the urine, or ...

  14. Heel pain

    MedlinePlus

    Pain - heel ... Heel pain is most often the result of overuse. However, it may be caused by an injury. Your heel ... on the heel Conditions that may cause heel pain include: Swelling and pain in the Achilles tendon ...

  15. The genetics of pain and pain inhibition.

    PubMed Central

    Mogil, J S; Sternberg, W F; Marek, P; Sadowski, B; Belknap, J K; Liebeskind, J C

    1996-01-01

    The present review summarizes the current state of knowledge about the genetics of pain-related phenomena and illustrates the scope and power of genetic approaches to the study of pain. We focus on work performed in our laboratories in Jastrzebiec, Poland; Portland, OR; and Los Angeles, which we feel demonstrates the continuing usefulness of classical genetic approaches, especially when used in combination with newly available molecular genetic techniques. PMID:8610166

  16. Synergistic effects of pain intensity and anxiety sensitivity in relation to anxiety and depressive symptoms and disorders among economically disadvantaged latinos in a community-based primary care setting.

    PubMed

    Velasco, Ricardo Valdés; Bakhshaie, Jafar; Walker, Rheeda L; Viana, Andres G; Garza, Monica; Ochoa-Perez, Melissa; Paulus, Daniel J; Robles, Zuzuky; Valdivieso, Jeanette; Zvolensky, Michael J

    2016-10-01

    The present investigation examined the interactive effects of anxiety sensitivity and pain intensity in relation to anxious arousal, social anxiety, and depressive symptoms and disorders among 203 Latino adults with an annual income of less than $30,000 (84.4% female; Mage=38.9, SD=11.3 and 98.6% used Spanish as their first language) who attended a community-based primary healthcare clinic. As expected, the interaction between anxiety sensitivity and pain intensity was significantly related to increased anxious arousal, social anxiety, and depressive symptoms as well as number of depressive/anxiety disorder diagnoses. The form of the significant interactions indicated that participants reporting co-occurring higher levels of anxiety sensitivity and pain intensity evinced the greatest levels of anxious arousal, social anxiety, and depressive symptoms as well as higher levels of depressive and anxiety disorders. These data provide novel empirical evidence suggesting that there is clinically-relevant interplay between anxiety sensitivity and pain intensity in regard to a relatively wide array of anxiety and depressive variables among Latinos in a primary care medical setting.

  17. Comparison Between Soluble ST2 and High-Sensitivity Troponin I in Predicting Short-Term Mortality for Patients Presenting to the Emergency Department With Chest Pain

    PubMed Central

    Marino, Rossella; Magrini, Laura; Orsini, Francesca; Russo, Veronica; Cardelli, Patrizia; Salerno, Gerardo; Hur, Mina

    2017-01-01

    Background High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. Methods Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. Results The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P<0.0001). In all patients, the sST2 level at arrival showed higher independent predictive power than hs-cTnI (odds ratio [OR] 20.13, P<0.0001 and OR 2.61, P<0.0008, respectively). sST2 at ED arrival showed a greater prognostic value for cardiovascular events in STEMI (area under the curve [AUC] 0.80, P<0.001) than NSTEMI patients (AUC 0.72, P<0.05). Overall, 51% of the STEMI patients with an sST2 value>35 ng/mL at ED arrival died during the 30-day follow-up. Conclusions sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value >35 ng/mL at ED arrival showed the highest predictive power for short-term mortality. PMID:28029000

  18. Sensitive and specific identification by polymerase chain reaction of Eimeria tenella and Eimeria maxima, important protozoan pathogens in laboratory avian facilities

    PubMed Central

    Lee, Hyun-A; Hong, Sunhwa; Chung, Yungho

    2011-01-01

    Eimeria tenella and Eimeria maxima are important pathogens causing intracellular protozoa infections in laboratory avian animals and are known to affect experimental results obtained from contaminated animals. This study aimed to find a fast, sensitive, and efficient protocol for the molecular identification of E. tenella and E. maxima in experimental samples using chickens as laboratory avian animals. DNA was extracted from fecal samples collected from chickens and polymerase chain reaction (PCR) analysis was employed to detect E. tenella and E. maxima from the extracted DNA. The target nucleic acid fragments were specifically amplified by PCR. Feces secreting E. tenella and E. maxima were detected by a positive PCR reaction. In this study, we were able to successfully detect E. tenella and E. maxima using the molecular diagnostic method of PCR. As such, we recommended PCR for monitoring E. tenella and E. maxima in laboratory avian facilities. PMID:21998616

  19. Effects of night time road traffic noise—an overview of laboratory and field studies on noise dose and subjective noise sensitivity

    NASA Astrophysics Data System (ADS)

    Öhrström, E.; Rylander, R.; Björkman, M.

    1988-12-01

    This paper presents an overview of research on sleep and noise at the Department of Environmental Hygiene, University of Gothenburg. Different methods were developed to study primary and after effects of night time road traffic noise on sleep. Three one-week laboratory experiments were undertaken to study the relevance of different noise descriptors— Leq, maximum peak noise level and number of events with high peak noise levels—for sleep disturbance effects. The noise exposure was either single noise evenys or a continuous, even road traffic noise. It was concluded that Leq was not related to sleep disturbance effects. Peak noise levels were significantly related to subjective sleep quality and body movements. Results from a third continuing study showed that there is a threshold for effects of the number of single noise events on sleep quality. Habituation to noise among subjects with differing noise sensitivity was studied in a two-week experiment. A significant noise effect on subjective sleep quality was found among sensitive subjects only. No habituation was seen for the negative influence of noise on sleep quality, mood and performance. Long-term effects of road traffic noise were also investigated in a field survey among 106 individuals. This study revealed the presence of a decrease in sleep quality as well as psycho-social effects on tiredness and mood, together with increased reports of headaches and nervous stomach. As in the laboratory study, sensitive individuals were more affected by noise than less sensitive individuals.

  20. 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.

  1. Intra- and inter-laboratory reproducibility and accuracy of the LuSens assay: A reporter gene-cell line to detect keratinocyte activation by skin sensitizers.

    PubMed

    Ramirez, Tzutzuy; Stein, Nadine; Aumann, Alexandra; Remus, Tina; Edwards, Amber; Norman, Kimberly G; Ryan, Cindy; Bader, Jackie E; Fehr, Markus; Burleson, Florence; Foertsch, Leslie; Wang, Xiaohong; Gerberick, Frank; Beilstein, Paul; Hoffmann, Sebastian; Mehling, Annette; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-04-01

    Several non-animal methods are now available to address the key events leading to skin sensitization as defined by the adverse outcome pathway. The KeratinoSens assay addresses the cellular event of keratinocyte activation and is a method accepted under OECD TG 442D. In this study, the results of an inter-laboratory evaluation of the "me-too" LuSens assay, a bioassay that uses a human keratinocyte cell line harboring a reporter gene construct composed of the rat antioxidant response element (ARE) of the NADPH:quinone oxidoreductase 1 gene and the luciferase gene, are described. Earlier in-house validation with 74 substances showed an accuracy of 82% in comparison to human data. When used in a battery of non-animal methods, even higher predictivity is achieved. To meet European validation criteria, a multicenter study was conducted in 5 laboratories. The study was divided into two phases, to assess 1) transferability of the method, and 2) reproducibility and accuracy. Phase I was performed by testing 8 non-coded test substances; the results showed a good transferability to naïve laboratories even without on-site training. Phase II was performed with 20 coded test substances (performance standards recommended by OECD, 2015). In this phase, the intra- and inter-laboratory reproducibility as well as accuracy of the method was evaluated. The data demonstrate a remarkable reproducibility of 100% and an accuracy of over 80% in identifying skin sensitizers, indicating a good concordance with in vivo data. These results demonstrate good transferability, reliability and accuracy of the method thereby achieving the standards necessary for use in a regulatory setting to detect skin sensitizers.

  2. Pain and nociception: mechanisms of cancer-induced bone pain.

    PubMed

    Falk, Sarah; Dickenson, Anthony H

    2014-06-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.

  3. The effects of experimental muscle and skin pain on the static stretch sensitivity of human muscle spindles in relaxed leg muscles

    PubMed Central

    Birznieks, Ingvars; Burton, Alexander R; Macefield, Vaughan G

    2008-01-01

    Animal studies have shown that noxious inputs onto γ-motoneurons can cause an increase in the activity of muscle spindles, and it has been proposed that this causes a fusimotor-driven increase in muscle stiffness that is believed to underlie many chronic pain syndromes. To test whether experimental pain also acts on the fusimotor system in humans, unitary recordings were made from 19 spindle afferents (12 Ia, 7 II) located in the ankle and toe extensors or peronei muscles of awake human subjects. Muscle pain was induced by bolus intramuscular injection of 0.5 ml 5% hypertonic saline into tibialis anterior (TA); skin pain was induced by 0.2 ml injection into the overlying skin. Changes in fusimotor drive to the muscle spindles were inferred from changes in the mean discharge frequency and discharge variability of spindle endings in relaxed muscle. During muscle pain no afferents increased their discharge activity: seven afferents (5 Ia, 2 II) showed a decrease and six (4 Ia, 2 II) afferents were not affected. During skin pain of 13 afferents discharge rate increased in one (Ia) and decreased in two (1 Ia, 1 II). On average, the overall discharge rate decreased during muscle pain by 6.1% (P < 0.05; Wilcoxon), but remained essentially the same during skin pain. There was no detectable correlation between subjective pain level and the small change in discharge rate of muscle spindles. Irrespective of the type of pain, discharge variability parameters were not influenced (P > 0.05; Wilcoxon). We conclude that, contrary to the ‘vicious cycle’ hypothesis, acute activation of muscle or skin nociceptors does not cause a reflex increase in fusimotor drive in humans. Rather, our results are more aligned with the pain adaptation model, based on clinical studies predicting pain-induced reductions of agonist muscle activity. PMID:18403422

  4. 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

  5. Development and sensitivity of a 12-h laboratory test with Daphnia magna Straus based on avoidance of pulp mill effluents.

    PubMed

    Rosa, R; Moreira-Santos, M; Lopes, I; Picado, A; Mendonça, E; Ribeiro, R

    2008-11-01

    Studies on avoidance of contaminants by aquatic organisms verified that such behavior may have crucial ecological implications. Yet, avoidance tests have not been considered in ecological risk assessments. This study aimed at developing a short-term test with Daphnia magna Straus based on avoidance of pulp mill effluents and at comparing its sensitivity to the standard 21 d D. magna reproduction test. The avoidance effective dilution values (12 h EDil20 and EDil50) were as sensitive as the 21 d EDil20 and EDil50 values for reproduction. Therefore, this easily standardizable short-term test can be recommended as a valuable complementary tool in ecological risk assessments.

  6. Cancer pain

    SciTech Connect

    Swerdlow, M.; Ventafridda, V.

    1987-01-01

    This book contains 13 chapters. Some of the chapter titles are: Importance of the Problem; Neurophysiology and Biochemistry of Pain; Assessment of Pain in Patients with Cancer; Drug Therapy; Chemotherapy and Radiotherapy for Cancer Pain; Sympton Control as it Relates to Pain Control; and Palliative Surgery in Cancer Pain Treatment.

  7. Identifying the most sensitive and specific sign and symptom combinations for cholera: results from an analysis of laboratory-based surveillance data from Haiti, 2012-2013.

    PubMed

    Lucien, Mentor Ali Ber; Schaad, Nicolas; Steenland, Maria W; Mintz, Eric D; Emmanuel, Rossignol; Freeman, Nicole; Boncy, Jacques; Adrien, Paul; Joseph, Gerard A; Katz, Mark A

    2015-04-01

    Since October 2010, over 700,000 cholera cases have been reported in Haiti. We used data from laboratory-based surveillance for diarrhea in Haiti to evaluate the sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the cholera case definitions recommended by the World Health Organization (WHO). From April 2012 to May 2013, we tested 1,878 samples from hospitalized patients with acute watery diarrhea; 1,178 (62.7%) yielded Vibrio cholerae O1. The sensitivity and specificity of the WHO case definition for cholera in an epidemic setting were 91.3% and 43.1%, respectively, and the PPV and NPV were 72.8% and 74.8%, respectively. The WHO case definition for cholera in an area where cholera is not known to be present had lower sensitivity (63.1%) and NPV (55.1%) but higher specificity (74.2%) and PPV (80.0%). When laboratory diagnostic testing is not immediately available, clinicians can evaluate signs and symptoms to more accurately identify cholera patients.

  8. Experimental pain responses in children with chronic pain and in healthy children: How do they differ?

    PubMed Central

    Tsao, Jennie CI; Evans, Subhadra; Seidman, Laura C; Zeltzer, Lonnie K

    2012-01-01

    BACKGROUND: Extant research comparing laboratory pain responses of children with chronic pain with healthy controls is mixed, with some studies indicating lower pain responsivity for controls and others showing no differences. Few studies have included different pain modalities or assessment protocols. OBJECTIVES: To compare pain responses among 26 children (18 girls) with chronic pain and matched controls (mean age 14.8 years), to laboratory tasks involving thermal heat, pressure and cold pain. Responses to cold pain were assessed using two different protocols: an initial trial of unspecified duration and a second trial of specified duration. METHODS: Four trials of pressure pain and of thermal heat pain stimuli, all of unspecified duration, were administered, as well as the two cold pain trials. Heart rate and blood pressure were assessed at baseline and after completion of the pain tasks. RESULTS: Pain tolerance and pain intensity did not differ between children with chronic pain and controls for the unspecified trials. For the specified cold pressor trial, 92% of children with chronic pain completed the entire trial compared with only 61.5% of controls. Children with chronic pain exhibited a trend toward higher baseline and postsession heart rate and reported more anxiety and depression symptoms compared with control children. CONCLUSIONS: Contextual factors related to the fixed trial may have exerted a greater influence on pain tolerance in children with chronic pain relative to controls. Children with chronic pain demonstrated a tendency toward increased arousal in anticipation of and following pain induction compared with controls. PMID:22518373

  9. Foetal pain?

    PubMed

    Derbyshire, Stuart W G

    2010-10-01

    The majority of commentary on foetal pain has looked at the maturation of neural pathways to decide a lower age limit for foetal pain. This approach is sensible because there must be a minimal necessary neural development that makes pain possible. Very broadly, it is generally agreed that the minimal necessary neural pathways for pain are in place by 24 weeks gestation. Arguments remain, however, as to the possibility of foetal pain before or after 24 weeks. Some argue that the foetus can feel pain earlier than 24 weeks because pain can be supported by subcortical structures. Others argue that the foetus cannot feel pain at any stage because it is maintained in a state of sedation in the womb and lacks further neural and conceptual development necessary for pain. Much of this argument rests on the definition of terms such as 'wakefulness' and 'pain'. If a behavioural and neural reaction to a noxious stimulus is considered sufficient for pain, then pain is possible from 24 weeks and probably much earlier. If a conceptual subjectivity is considered necessary for pain, however, then pain is not possible at any gestational age. Regardless of how pain is defined, it is clear that pain for conceptual beings is qualitatively different than pain for non-conceptual beings. It is therefore a mistake to draw an equivalence between foetal pain and pain in the older infant or adult.

  10. Neck Pain

    MedlinePlus

    ... injuries and conditions that cause pain and restrict motion. Neck pain causes include: Muscle strains. Overuse, such ... body then forms bone spurs that affect joint motion and cause pain. Nerve compression. Herniated disks or ...

  11. Ankle pain

    MedlinePlus

    Pain - ankle ... Ankle pain is often due to an ankle sprain. An ankle sprain is an injury to the ligaments, which ... the joint. In addition to ankle sprains, ankle pain can be caused by: Damage or swelling of ...

  12. Knee pain

    MedlinePlus

    Pain - knee ... Knee pain can have different causes. Being overweight puts you at greater risk for knee problems. Overusing your knee can trigger knee problems that cause pain. If you have a history of arthritis, it ...

  13. Elbow pain

    MedlinePlus

    Pain - elbow ... Elbow pain can be caused by many problems. A common cause in adults is tendinitis . This is inflammation and ... a partial dislocation ). Other common causes of elbow pain are: Bursitis -- inflammation of a fluid-filled cushion ...

  14. Eye pain

    MedlinePlus

    Ophthalmalgia; Pain - eye ... Pain in the eye can be an important symptom of a health problem. Make sure you tell your health care provider if you have eye pain that does not go away. Tired eyes or ...

  15. Wrist pain

    MedlinePlus

    Pain - wrist; Pain - carpal tunnel; Injury - wrist; Arthritis - wrist; Gout - wrist; Pseudogout - wrist ... Carpal tunnel syndrome: A common cause of wrist pain is carpal tunnel syndrome . You may feel aching, ...

  16. Foot pain

    MedlinePlus

    Pain - foot ... Foot pain may be due to: Aging Being on your feet for long periods of time Being overweight A ... sports activity Trauma The following can cause foot pain: Arthritis and gout . Common in the big toe, ...

  17. Phantom Pain

    MedlinePlus

    ... be an effective treatment for some types of chronic pain. In acupuncture, the practitioner inserts extremely fine, sterilized ... and Stroke. http://www.ninds.nih.gov/disorders/chronic_pain/detail_chronic_pain.htm. Accessed Sept. 16, 2014. ...

  18. Hip pain

    MedlinePlus

    ... pain involves any pain in or around the hip joint. You may not feel pain from your hip ... 2012:chap 48. Read More Hip fracture surgery Hip joint replacement Patient Instructions Hip fracture - discharge Hip or ...

  19. Depression, Pain, and Pain Behavior.

    ERIC Educational Resources Information Center

    Keefe, Francis J.; And Others

    1986-01-01

    Examined the degree to which depression predicted pain and pain behavior. The Beck Depression Inventory was administered to 207 low back pain patients. Depression and physical findings were the most important predictors of pain and pain behavior. Depression proved significant even after controlling for important demographic and medical status…

  20. Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

    PubMed Central

    Yang, Linlin; Li, Quanmin; Liu, Xinming; Liu, Shiguang

    2016-01-01

    Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy. PMID:27608006

  1. Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy.

    PubMed

    Yang, Linlin; Li, Quanmin; Liu, Xinming; Liu, Shiguang

    2016-09-05

    Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause-effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.

  2. 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)

  3. Carba NP as a simpler, rapid, cost-effective, and a more sensitive alternative to other phenotypic tests for detection of carbapenem resistance in routine diagnostic laboratories

    PubMed Central

    Shinde, Shivani; Gupta, Rajarshi; Raut, Shweta S.; Nataraj, Gita; Mehta, Preeti R.

    2017-01-01

    PURPOSE: Resistance to carbapenems due to carbapenemases has been increasingly noticed in Enterobacteriaceae. Clinical and Laboratory Standards Institute (CLSI) has recommended the latest Carba NP (CNP) test as a confirmatory test for carbapenemase production in Enterobacteriaceae. Low sensitivity of disk diffusion (DD) and modified Hodge test (MHT) may result in missing out of resistant strains which can adversely affect clinical management. The present study compares three phenotypic tests - CNP test, DD, and MHT for detection of carbapenemase production. MATERIALS AND METHODS: Four hundred consecutive, nonduplicate Enterobacteriaceae isolates were tested for carbapenem resistance using ertapenem disc (10 μg) by Kirby–Bauer DD method, MHT, and CNP. These tests were performed and interpreted as per the CLSI standards. CNP was considered to be the reference test for comparison. Sensitivity, specificity, and accuracy rates for ertapenem DD and MHT were calculated. RESULTS: One hundred and six out of 400 strains were positive by CNP test. Of the 294 CNP-negative strains, 28 were resistant by DD and 18 were resistant by MHT. Of the 106 CNP-positive strains, 82 were resistant and 16 were intermediate by DD while 76 were positive by MHT ertapenem DD had a sensitivity and specificity of 66.04% and 90.48%, respectively. Sensitivity and specificity of MHT were 54.72% and 93.88%, respectively. There was considerable discordance between all the three tests. CONCLUSION: As a rapid, simple, and cost-effective test with a greater capability greater to detect carbapenemase producers, CNP can be implemented in routine diagnostic laboratories, thereby benefiting patient care and antimicrobial stewardship. PMID:28367024

  4. TRPA1 mediates formalin-induced pain.

    PubMed

    McNamara, Colleen R; Mandel-Brehm, Josh; Bautista, Diana M; Siemens, Jan; Deranian, Kari L; Zhao, Michael; Hayward, Neil J; Chong, Jayhong A; Julius, David; Moran, Magdalene M; Fanger, Christopher M

    2007-08-14

    The formalin model is widely used for evaluating the effects of analgesic compounds in laboratory animals. Injection of formalin into the hind paw induces a biphasic pain response; the first phase is thought to result from direct activation of primary afferent sensory neurons, whereas the second phase has been proposed to reflect the combined effects of afferent input and central sensitization in the dorsal horn. Here we show that formalin excites sensory neurons by directly activating TRPA1, a cation channel that plays an important role in inflammatory pain. Formalin induced robust calcium influx in cells expressing cloned or native TRPA1 channels, and these responses were attenuated by a previously undescribed TRPA1-selective antagonist. Moreover, sensory neurons from TRPA1-deficient mice lacked formalin sensitivity. At the behavioral level, pharmacologic blockade or genetic ablation of TRPA1 produced marked attenuation of the characteristic flinching, licking, and lifting responses resulting from intraplantar injection of formalin. Our results show that TRPA1 is the principal site of formalin's pain-producing action in vivo, and that activation of this excitatory channel underlies the physiological and behavioral responses associated with this model of pain hypersensitivity.

  5. Basic science of pain.

    PubMed

    DeLeo, Joyce A

    2006-04-01

    The origin of the theory that the transmission of pain is through a single channel from the skin to the brain can be traced to the philosopher and scientist René Descartes. This simplified scheme of the reflex was the beginning of the development of the modern doctrine of reflexes. Unfortunately, Descartes' reflex theory directed both the study and treatment of pain for more than 330 years. It is still described in physiology and neuroscience textbooks as fact rather than theory. The gate control theory proposed by Melzack and Wall in 1965 rejuvenated the field of pain study and led to further investigation into the phenomena of spinal sensitization and central nervous system plasticity, which are the potential pathophysiologic correlates of chronic pain. The processing of pain takes place in an integrated matrix throughout the neuroaxis and occurs on at least three levels-at peripheral, spinal, and supraspinal sites. Basic strategies of pain control monopolize on this concept of integration by attenuation or blockade of pain through intervention at the periphery, by activation of inhibitory processes that gate pain at the spinal cord and brain, and by interference with the perception of pain. This article discusses each level of pain modulation and reviews the mechanisms of action of opioids and potential new analgesics. A brief description of animal models frames a discussion about recent advances regarding the role of glial cells and central nervous system neuroimmune activation and innate immunity in the etiology of chronic pain states. Future investigation into the discovery and development of novel, nonopioid drug therapy may provide needed options for the millions of patients who suffer from chronic pain syndromes, including syndromes in which the pain originates from peripheral nerve, nerve root, spinal cord, bone, muscle, and disc.

  6. Acute abdominal pain.

    PubMed

    Stone, R

    1998-01-01

    Abdominal pain is among the most frequent ailments reported in the office setting and can account for up to 40% of ailments in the ambulatory practice. Also, it is in the top three symptoms of patients presenting to emergency departments (ED) and accounts for 5-10% of all ED primary presenting ailments. There are several common sources for acute abdominal pain and many for subacute and chronic abdominal pain. This article explores the history-taking, initial evaluation, and examination of the patient presenting with acute abdominal pain. The goal of this article is to help differentiate one source of pain from another. Discussion of acute cholecystitis, pancreatitis, appendicitis, ectopic pregnancy, diverticulitis, gastritis, and gastroenteritis are undertaken. Additionally, there is discussion of common laboratory studies, diagnostic studies, and treatment of the patient with the above entities.

  7. Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats.

    PubMed

    Hassler, Shayne N; Johnson, Kathia M; Hulsebosch, Claire E

    2014-11-01

    Chronic neuropathic pain is a common consequence of spinal cord injury (SCI), develops over time and negatively impacts quality of life, often leading to substance abuse and suicide. Recent evidence has demonstrated that reactive oxygen species (ROS) play a role in contributing to neuropathic pain in SCI animal models. This investigation examines four compounds that reduce ROS and the downstream lipid peroxidation products, apocynin, 4-oxo-tempo, U-83836E, and tirilazad, and tests if these compounds can reduce nocioceptive behaviors in chronic SCI animals. Apocynin and 4-oxo-tempo significantly reduced abnormal mechanical hypersensitivity measured in forelimbs and hindlimbs in a model of chronic SCI-induced neuropathic pain. Thus, compounds that inhibit ROS or lipid peroxidation products can be used to ameliorate chronic neuropathic pain. We propose that the application of compounds that inhibit reactive oxygen species (ROS) and related downstream molecules will also reduce the behavioral measures of chronic neuropathic pain. Injury or trauma to nervous tissue leads to increased concentrations of ROS in the surviving tissue. Further damage from ROS molecules to dorsal lamina neurons leads to membrane excitability, the physiological correlate of chronic pain. Chronic pain is difficult to treat with current analgesics and this research will provide a novel therapy for this disease.

  8. Shoulder pain

    MedlinePlus

    Pain - shoulder ... changes around the rotator cuff can cause shoulder pain. You may have pain when lifting the arm above your head or ... The most common cause of shoulder pain occurs when rotator cuff tendons ... The tendons become inflamed or damaged. This condition ...

  9. Pelvic Pain

    MedlinePlus

    Pelvic pain occurs mostly in the lower abdomen area. The pain might be steady, or it might come and go. If the pain is severe, it might get in the way ... re a woman, you might feel a dull pain during your period. It could also happen during ...

  10. Sensitivity of an indigenous amphipod (Corophium colo) to chemical contaminants in laboratory toxicity tests conducted with sediments from Sydney Harbor, Australia, and vicinity.

    PubMed

    McCready, Stephanie; Greely, Christopher R; Hyne, Ross V; Birch, Gavin F; Long, Edward R

    2005-10-01

    Laboratory survival tests were conducted with an indigenous infaunal amphipod, Corophium colo, on 103 sediment samples from Sydney Harbor (NSW, Australia) and vicinity, containing a wide range of chemicals and concentrations. The present study describes the sensitivity of C. colo to the sediments and compares the results to data for North American amphipods (Rhepoxynius abronius and Ampelisca abdita) previously used to establish and validate sediment-quality guidelines (SQGs). The incidence of toxicity increased with increasing contamination, as indicated by increasing numbers of SQGs exceeded and increasing mean SQG quotients. The incidence of highly toxic results (p < 0.05 and mean amphipod survival of < 80% that of controls) for highly contaminated samples was approximately half (28-40%) that of a large U.S. database (74%). The incidence of highly toxic responses for samples with intermediate levels of contamination also was lower in the present study (5-13%) compared to the results in large U.S. studies (approximately 30-50%). Corophium colo reburial tests showed greater sensitivity compared to survival tests, with a maximum incidence of statistically significant responses in moderately contaminated sediments of 70%. The present study showed that adult Corophium organisms are suitable for testing lethal responses in highly contaminated sediments (i.e., with mean effects range-median quotients of >1.5). Reburial results provide additional sensitivity.

  11. Grainsize-sensitive viscoelastic relaxation in olivine: Towards a robust laboratory-based model for seismological application

    NASA Astrophysics Data System (ADS)

    Jackson, Ian; Faul, Ulrich H.; Suetsugu, Daisuke; Bina, Craig; Inoue, Toru; Jellinek, Mark

    2010-11-01

    Torsional forced oscillation data for a newly prepared specimen of dry, melt-free polycrystalline Fo90 olivine of 3.1 μm average grainsize have been used to reassess alternative strategies for the parameterisation of grainsize-sensitive viscoelastic relaxation. Our previously employed extended Burgers model has been modified by prescribing anharmonic temperature and pressure dependence of the effective unrelaxed shear modulus GU relative to its value GUR at reference values of temperature (TR = 900 °C) and pressure (PR = 0.2 GPa). The modified model provides an excellent description of forced-oscillation data for the newly prepared olivine polycrystal at temperatures of 900-1200 °C and oscillation periods of 1-1000 s, with a value of GUR that is significantly (7%) less than the strictly anharmonic value for the same conditions (TR,PR). This modulus deficit is interpreted to reflect the impact of elastically accommodated grain-boundary sliding tentatively associated with a newly recognised 'plateau' with Q-1 ∼ 0.01 that moves across the seismic band from long to short period with increasing temperature between 750 and 950 °C. The modified Burgers model is preferred over the Andrade-pseudoperiod and power-law Q-1 alternatives for its flexibility in specifying a distribution D(τ) of anelastic relaxation times that can account for both the monotonic background dissipation and the superimposed dissipation peak of elastically accommodated grain-boundary sliding, along with the associated modulus dispersion. Such 'background + peak' Burgers models, seamlessly describing the transition from (anharmonic) elasticity to grainsize-sensitive viscoelastic behaviour, have been fitted to the data for individual polycrystalline olivine specimens and suites of olivine polycrystals. Extrapolation of the model for our suite of essentially melt-free olivine polycrystals to mantle grain sizes and pressures suggest a significant contribution from grain-boundary relaxation under

  12. Neuropathic pain in leprosy.

    PubMed

    Raicher, Irina; Stump, Patrick Raymond Nicolas Andre Ghislain; Baccarelli, Rosemari; Marciano, Lucia H S C; Ura, Somei; Virmond, Marcos C L; Teixeira, Manoel Jacobsen; Ciampi de Andrade, Daniel

    2016-01-01

    Nerve impairment is a key clinical aspect of leprosy and may present the distribution of mononeuropathy or multiple nerve trunks, small cutaneous nerve fibers, and free nerve endings. The clinical range of leprosy is determined by individual cell-mediated immune response to infection that also may play a role in different types of pain syndromes in leprosy. Previous studies reported a high prevalence of neuropathic pain in leprosy. In an Ethiopian study with 48 patients, pure nociceptive pain was experienced by 43% of patients and pure neuropathic pain (NeP) by 11% of patients. In an Indian study, 21.8% of leprosy patients had pain with neuropathic characteristics. These rates underlie the need to develop tools for the early diagnosis and detection of infection and its complications, such as nerve damage and pain. In a larger sample with leprosy-associated NeP (n = 90), we have applied the Douleur Neuropathique en 4 questions (DN4) and found sensitivity = 97.1% and specificity = 57.9%. The high sensitivity of this tool in leprosy patients suggests that it could be a valuable tool to screen for neuropathic pain in this population and could be used as part of health care programs aimed at detecting, treating, and rehabilitating leprosy in endemic areas.

  13. Pathophysiology of Post Amputation Pain

    DTIC Science & Technology

    2014-12-01

    nociception and pain : analysis through imaging. Proc Natl Acad Sci U S A 1999;96:7668-74. 44. Casey KL, Minoshima S, Morrow TJ, Koeppe RA. Comparison of...trials. Eur J Pain 2006;10:77-88. 95. Dotson RM. Clinical neurophysiology laboratory tests to assess the nociceptive system in humans. J Clin...Award Number: W81XWH-11-1-0815 TITLE: Pathophysiology of Post Amputation Pain PRINCIPAL INVESTIGATOR: Dr. R. Norman Harden CONTRACTING

  14. Systems Genetics of Chronic Pain

    DTIC Science & Technology

    2013-09-01

    affecting inter-individual variability in chronic pain nociception using a state of the art population of laboratory mice (Diversity Outbred mice...approaches for the discovery of new genes related to chronic pain nociception . Genetic linkage mapping in DO mice produced a much more precise and efficient...1 AD_________________ Award Number: W81XWH-11-1-0762 TITLE: Systems Genetics of Chronic Pain

  15. UP3005, a Botanical Composition Containing Two Standardized Extracts of Uncaria gambir and Morus alba, Improves Pain Sensitivity and Cartilage Degradations in Monosodium Iodoacetate-Induced Rat OA Disease Model

    PubMed Central

    Yimam, Mesfin; Lee, Young-Chul; Kim, Tae-Woo; Moore, Breanna; Jiao, Ping; Hong, Mei; Kim, Hyun-Jin; Nam, Jeong-Bum; Kim, Mi-Ran; Oh, Jin-Sun; Cleveland, Sabrina; Hyun, Eu-Jin; Chu, Min; Jia, Qi

    2015-01-01

    Osteoarthritis (OA) is a multifactorial disease primarily noted by cartilage degradation in association with inflammation that causes significant morbidity, joint pain, stiffness, and limited mobility. Present-day management of OA is inadequate due to the lack of principal therapies proven to be effective in hindering disease progression where symptomatic therapy focused approach masks the actual etiology leading to irreversible damage. Here, we describe the effect of UP3005, a composition containing a proprietary blend of two standardized extracts from the leaf of Uncaria gambir and the root bark of Morus alba, in maintaining joint structural integrity and alleviating OA associated symptoms in monosodium-iodoacetate- (MIA-) induced rat OA disease model. Pain sensitivity, micro-CT, histopathology, and glycosaminoglycans (GAGs) level analysis were conducted. Diclofenac at 10 mg/kg was used as a reference compound. UP3005 resulted in almost a complete inhibition in proteoglycans degradation, reductions of 16.6% (week 4), 40.5% (week 5), and 22.0% (week 6) in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, minimal visual subchondral bone damage, and statistically significant increase in bone mineral density when compared to the vehicle control with MIA. Therefore, UP3005 could potentially be considered as an alternative therapy from natural sources for the treatment of OA and/or its associated symptoms. PMID:25802546

  16. Sexual pain.

    PubMed

    Boardman, Lori A; Stockdale, Colleen K

    2009-12-01

    Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain.

  17. Multimodal nociceptive mechanisms underlying chronic pelvic pain

    PubMed Central

    HELLMAN, Kevin M.; PATANWALA, Insiyyah Y.; POZOLO, Kristen E.; TU, Frank F.

    2015-01-01

    Objective To evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain and/or painful bladder syndrome/interstitial cystitis. Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. Study Design As part of a larger study on pelvic floor pain dysfunction and bladder pain sensitivity, we compared a measure of mechanical pain sensitivity, pressure pain thresholds, between women with pelvic pain and pain-free controls. We also assessed a novel pain measure using degree and duration of post-exam pain aftersensation, and conducted structural and functional assessments of the pelvic floor to account for any potential confounding. Phenotypic specificity of pelvic floor measures was assessed with receiver-operator characteristic curves adjusted for prevalence. Results A total of 23 women with chronic pelvic pain, 23 painful bladder syndrome, and 42 pain-free controls completed the study. Women with chronic pelvic pain or painful bladder syndrome exhibited enhanced pain sensitivity with lower pressure pain thresholds (1.18 [interquartile range: 0.87–1.41] kg/cm2) than pain-free participants (1.48 [1.11–1.76] kg/cm2; p<0.001) and prolonged pain aftersensation (3.5 [0–9] vs 0 [0–1] minutes; p< 0.001). Although genital hiatus (p<0.01) was wider in women with chronic pelvic pain there were no consistently observed group differences in pelvic floor anatomy, muscle tone or strength. The combination of pressure pain thresholds and aftersensation duration correlated with severity of pelvic floor tenderness (R2 =41–51, p’s< 0.01). Even after adjustment for prevalence, the combined metrics discriminated pain-free controls from women with chronic pelvic pain or painful bladder syndrome (area under the curve=0.87). Conclusion Both experimental assessment of pelvic floor pain thresholds and measurement of sustained pain are independently associated with pelvic pain

  18. Effects of low levels of road traffic noise during the night: a laboratory study on number of events, maximum noise levels and noise sensitivity

    NASA Astrophysics Data System (ADS)

    Öhrström, E.

    1995-01-01

    The objective of the laboratory study presented here was to elucidate the importance of the number of noise events of a relatively low maximum noise level for sleep disturbance effects (body movements, subjective sleep quality, mood and performance). Twelve test persons slept eight nights under home-like laboratory settings. During four of these nights, each test person was exposed to 16, 32, 64 and 128 noise events respectively from recorded road traffic noise at a maximum noise level of 45 dB(A). All test persons (aged 20-42 years) considered themselves rather or very sensitive towards noise. The results show a significant decrease in subjective sleep quality at 32 noise events per night. At 64 noise events, 50% of the test persons experienced difficulties in falling asleep and, as compared with quiet nights, the time required to fall asleep was on average 12 minutes longer. The occurrence of body movements was significantly related to the reported number of awakenings, and the number of body movements was three times higher during the noisy periods of the night as compared with the quiet periods, indicating acute noise effects. The results of a vigilance test indicate that noise during the night might prolong the time needed to solve the test. Finally, and regardless of number of noise events, a significant increase in tiredness during the day was found after nights with noise exposure. In the paper comparisons are also made with earlier experiments using maximum noise levels of 50 and 60 dB(A).

  19. Autism Spectrum Disorder and Amplified Pain

    PubMed Central

    2015-01-01

    Among the core features of ASD, altered sensitivities in all modalities have been accorded increasing importance. Heightened sensitivity to pain and unusual expressions of and reaction to pain have not hitherto been widely recognised as a presenting feature of ASD in general paediatrics. Failure to recognise ASD as a common cause of pain can lead to late diagnosis, inappropriate treatment, distress, and further disability. Two cases are presented which illustrate the late presentation of Autism Spectrum Disorder (Asperger's Syndrome subtype) with chronic unusual pain. Conclusion. Pain in autism can be atypical in its experience and expression and for this reason may go unrecognised by physicians treating chronic pain disorders. PMID:26064754

  20. Salivary cytokines as a minimally-invasive measure of immune functioning in young children: correlates of individual differences and sensitivity to laboratory stress.

    PubMed

    Riis, Jenna L; Granger, Douglas A; DiPietro, Janet A; Bandeen-Roche, Karen; Johnson, Sara B

    2015-03-01

    There is growing interest in minimally-invasive measures of environmentally-responsive biological systems in developmental science. Contributing to that endeavor, this study explores the intercorrelations, correlates, and task-sensitivity of proinflammatory salivary cytokines in childhood. Saliva was sampled from 125 healthy five-year old children (49% male) across a series of cognitive and emotional challenge laboratory tasks. Samples were assayed for cytokines (IL-1β, IL-6, IL-8, TNFα), and markers of hypothalamic-pituitary-adrenal (HPA) and autonomic nervous system (ANS) activation (salivary cortisol and alpha-amylase [sAA]). Cytokines were positively intercorrelated and task-sensitivity varied. Except IL-8, cytokines were elevated in children with oral health issues and tobacco smoke exposure. Among boys, cytokines were positively related to sAA and negatively related to cortisol. The findings suggest that in healthy children, salivary cytokine levels reflect compartmentalized oral immune activity. Associations between ANS and HPA activity and cytokines in saliva may present opportunities for minimally-invasive methods to explore neuroendocrine-immune interactions during development.

  1. Pain Assessment

    MedlinePlus

    ... acupuncture, chiropractic care, massage or other manual therapies, yoga, herbal and nutritional therapies, or others. This information helps the health care provider understand the nature of the pain or the potential benefits of treatment. The goals of the comprehensive pain ...

  2. Anal Pain

    MedlinePlus

    ... change in bowel habit or rectal bleeding. A hemorrhoid that develops quickly or is particularly painful may ... your doctor. The blood clot of a thrombosed hemorrhoid, although painful, can't break loose and travel, ...

  3. Back Pain

    MedlinePlus

    ... specific points on the body. Some people with low back pain report that acupuncture helps relieve their symptoms. Massage. ... Accessed May 29, 2015. Adult acute and subacute low back pain. Bloomington, Minn.: Institute for Clinical Systems Improvement. http:// ...

  4. Period Pain

    MedlinePlus

    ... You may also have other symptoms, such as lower back pain, nausea, diarrhea, and headaches. Period pain is not ... Taking a hot bath Doing relaxation techniques, including yoga and meditation You might also try taking over- ...

  5. Finger pain

    MedlinePlus

    Pain - finger ... Nearly everyone has had finger pain at some time. You may have: Tenderness Burning Stiffness Numbness Tingling Coldness Swelling Change in skin color Redness Many conditions, such ...

  6. Back Pain

    MedlinePlus

    ... Oh, my aching back!", you are not alone. Back pain is one of the most common medical problems, ... 10 people at some point during their lives. Back pain can range from a dull, constant ache to ...

  7. Breast Pain

    MedlinePlus

    ... before your period and sometimes continuing through your menstrual cycle. The pain may be moderate or severe, and ... breasts. Throughout the month, not related to your menstrual cycle. Postmenopausal women sometimes have breast pain, but breast ...

  8. Hip Pain

    MedlinePlus

    ... clues about the underlying cause. Problems within the hip joint itself tend to result in pain on the ... tendons and other soft tissues that surround your hip joint. Hip pain can sometimes be caused by diseases ...

  9. The Nicotinic α6 Subunit Gene Determines Variability in Chronic Pain Sensitivity via Cross-inhibition of P2X2/3 Receptors

    PubMed Central

    Wieskopf, Jeffrey S.; Mathur, Jayanti; Limapichat, Walrati; Post, Michael R.; Al-Qazzaz, Mona; Sorge, Robert E.; Martin, Loren J.; Zaykin, Dmitri V.; Smith, Shad B.; Freitas, Kelen; Austin, Jean-Sebastien; Dai, Feng; Zhang, Jie; Marcovitz, Jaclyn; Tuttle, Alexander H.; Slepian, Peter M.; Clarke, Sarah; Drenan, Ryan M.; Janes, Jeff; Sharari, Shakir Al; Segall, Samantha K.; Aasvang, Eske K.; Lai, Weike; Bittner, Reinhard; Richards, Christopher I.; Slade, Gary D.; Kehlet, Henrik; Walker, John; Maskos, Uwe; Changeux, Jean-Pierre; Devor, Marshall; Maixner, William; Diatchenko, Luda; Belfer, Inna; Dougherty, Dennis A.; Su, Andrew I.; Lummis, Sarah C.R.; Damaj, M. Imad; Lester, Henry A.; Patapoutian, Ardem; Mogil, Jeffrey S.

    2016-01-01

    Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (i.e., α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6’s role in analgesia is at least partially due to direct interaction and cross-inhibition of α6* nAChRs with P2X2/3 receptors in DRG nociceptors. Finally, we establish relevance of our results to humans by the observation of genetic association in patients suffering from chronic postsurgical pain and temporomandibular pain. PMID:25972004

  10. Patellofemoral Pain.

    PubMed

    Dutton, Rebecca A; Khadavi, Michael J; Fredericson, Michael

    2016-02-01

    Patellofemoral pain is characterized by insidious onset anterior knee pain that is exaggerated under conditions of increased patellofemoral joint stress. A variety of risk factors may contribute to the development of patellofemoral pain. It is critical that the history and physical examination elucidate those risk factors specific to an individual in order to prescribe an appropriate and customized treatment plan. This article aims to review the epidemiology, risk factors, diagnosis, and management of patellofemoral pain.

  11. Anger inhibition and pain: conceptualizations, evidence and new directions.

    PubMed

    Burns, John W; Quartana, Phillip J; Bruehl, Stephen

    2008-06-01

    Anger and how anger is regulated appear to affect acute and chronic pain intensity. The inhibition of anger (anger-in), in particular, has received much attention, and it is widely believed that suppressing or inhibiting the verbal or physical expression of anger is related to increased pain severity. We examine theoretical accounts for expecting that anger inhibition should affect pain, and review evidence for this claim. We suggest that the evidence for a link between trait anger-in (the self-reported tendency to inhibit anger expression when angry) and acute and chronic pain severity is quite limited owing to a number of factors including a inadequate definition of trait anger-in embodied in the popular anger-in subscale of Spielberger's Anger Expression Inventory, and a strong overlap between trait anger-in scores and measures of general negative affect (NA). We argue that in order to determine whether something unique to the process of anger inhibition exerts direct effects on subsequent pain intensity, new conceptualizations and approaches are needed that go beyond self-report assessments of trait anger-in. We present one model of anger inhibition and pain that adopts elements of Wegner's ironic process theory of thought suppression. Findings from this emerging research paradigm indicate that state anger suppression (suppression manipulated in the laboratory) may indeed affect sensitivity to subsequent painful stimuli, and we outline potentially productive avenues of future inquiry that build on this model. We conclude that although studies employing correlational designs and self-reports of trait anger-in have not upheld the claim that anger inhibition affects pain severity, evidence from studies using new models suggests that actually inhibiting anger expression during a provocative event may increase perceived pain at a later time.

  12. 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.

  13. Intranasal oxytocin administration is associated with enhanced endogenous pain inhibition and reduced negative mood states

    PubMed Central

    Goodin, Burel R.; Anderson, Austen J. B.; Freeman, Emily L.; Bulls, Hailey W.; Robbins, Meredith T.; Ness, Timothy J.

    2014-01-01

    Objectives This study examined whether the administration of intranasal oxytocin was associated with pain sensitivity, endogenous pain inhibitory capacity, and negative mood states. Methods A total of 30 pain-free, young adults each completed three laboratory sessions on consecutive days. The first session (baseline) assessed ischemic pain sensitivity, endogenous pain inhibition via conditioned pain modulation (CPM), and negative mood using the Profile of Mood States (POMS). CPM was tested on the dominant forearm and ipsilateral masseter muscle using algometry (test stimulus) and the cold pressor task (conditioning stimulus; non-dominant hand). For the second and third sessions, participants initially completed the State-Trait Anxiety Inventory (STAI) and then self-administered a single (40IU/1mL) dose of intranasal oxytocin or placebo in a randomized counter-balanced order. Thirty minutes post-administration, participants again completed the STAI and repeated assessments of ischemic pain sensitivity and CPM followed by the POMS. Results Findings demonstrated that ischemic pain sensitivity did not significantly differ across the three study sessions. CPM at the masseter, but not the forearm, was significantly greater following administration of oxytocin compared to placebo. Negative mood was also significantly lower following administration of oxytocin compared to placebo. Similarly, anxiety significantly decreased following administration of oxytocin but not placebo. Discussion This study incorporated a placebo-controlled, double-blind, within-subjects crossover design with randomized administration of intranasal oxytocin and placebo. The data suggest that the administration of intranasal oxytocin may augment endogenous pain inhibitory capacity and reduce negative mood states including anxiety. PMID:25370147

  14. Temporomandibular pain

    PubMed Central

    Prasad, S Raghavendra; Kumar, N Ravi; Shruthi, HR; Kalavathi, SD

    2016-01-01

    Temporomandibular joint pain has various medical and dental etiological factors. The etiology of the temporomandibular joint pain is enigmatic, no single etiological factor is regarded as the cause. Its distribution is also not confined to a single area. This article presents the basic etiologic factors, its epidemiology, distribution of pain, classification of patients and the psychosocial behavior of patients suffering with temporomandibular pain. As overwhelming majority of medical and dental conditions/issues related to etiology of temporomandibular pain in patients have traditionally been presented and interpreted from the clinician's point of view. PMID:27601822

  15. 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.

  16. Therapeutic mechanisms of a mindfulness-based treatment for IBS: Effects on visceral sensitivity, catastrophizing, and affective processing of pain sensations

    PubMed Central

    Garland, Eric L.; Gaylord, Susan A.; Palsson, Olafur; Faurot, Keturah; Mann, J. Douglas; Whitehead, William E.

    2013-01-01

    Irritable bowel syndrome (IBS) is a prevalent functional disorder characterized by abdominal pain and hypervigilance to gastrointestinal sensations. We hypothesized that mindfulness training (MT), which promotes nonreactive awareness of emotional and sensory experience, may target underlying mechanisms of IBS including affective pain processing and catastrophic appraisals of gastrointestinal sensations. Seventy five female IBS patients were randomly assigned to participate in either 8 weeks of MT or a social support group. A theoretically grounded, multivariate path model tested therapeutic mediators of the effect of MT on IBS severity and quality of life. Results suggest that MT exerts significant therapeutic effects on IBS symptoms by promoting nonreactivity to gut-focused anxiety and catastrophic appraisals of the significance of abdominal sensations coupled with a refocusing of attention onto interoceptive data with less emotional interference. Hence, MT appears to target and ameliorate the underlying pathogenic mechanisms of IBS. PMID:22161025

  17. Abdominal Pain (Stomach Pain), Short-Term

    MedlinePlus

    ... myhealthfinder Immunization Schedules Nutrient Shortfall Questionnaire Abdominal Pain (Stomach Pain), Short-termJust about everyone has had a " ... time or another. But sudden severe abdominal pain (stomach pain), also called acute pain, shouldn't be ...

  18. Predicting skin sensitization potential and inter-laboratory reproducibility of a human Cell Line Activation Test (h-CLAT) in the European Cosmetics Association (COLIPA) ring trials.

    PubMed

    Sakaguchi, Hitoshi; Ryan, Cindy; Ovigne, Jean-Marc; Schroeder, Klaus R; Ashikaga, Takao

    2010-09-01

    Regulatory policies in Europe prohibited the testing of cosmetic ingredients in animals for a number of toxicological endpoints. Currently no validated non-animal test methods exist for skin sensitization. Evaluation of changes in cell surface marker expression in dendritic cell (DC)-surrogate cell lines represents one non-animal approach. The human Cell Line Activation Test (h-CLAT) examines the level of CD86 and CD54 expression on the surface of THP-1 cells, a human monocytic leukemia cell line, following 24h of chemical exposure. To examine protocol transferability, between-lab reproducibility, and predictive capacity, the h-CLAT has been evaluated by five independent laboratories in several ring trials (RTs) coordinated by the European Cosmetics Association (COLIPA). The results of the first and second RTs demonstrated that the protocol was transferable and basically had good between-lab reproducibility and predictivity, but there were some false negative data. To improve performance, protocol and prediction model were modified. Using the modified prediction model in the first and second RT, accuracy was improved. However, about 15% of the outcomes were not correctly identified, which exposes some of the limitations of the assay. For the chemicals evaluated, the limitation may due to chemical being a weak allergen or having low solubility (ex. alpha-hexylcinnamaldehyde). The third RT evaluated the modified prediction model and satisfactory results were obtained. From the RT data, the feasibility of utilizing cell lines as surrogate DC in development of in vitro skin sensitization methods shows promise. The data also support initiating formal pre-validation of the h-CLAT in order to fully understand the capabilities and limitations of the assay.

  19. Complex regional pain syndrome

    PubMed Central

    Sebastin, Sandeep J

    2011-01-01

    Complex regional pain syndrome (CRPS) previously known as reflex sympathetic dystrophy is a chronic neurological disorder involving the limbs characterized by disabling pain, swelling, vasomotor instability, sudomotor abnormality, and impairment of motor function. CRPS is not uncommon after hand surgery and may complicate post-operative care. There is no specific diagnostic test for CRPS and the diagnosis is based on history, clinical examination, and supportive laboratory findings. Recent modifications to diagnostic criteria have enabled clinicians to diagnose this disease more consistently. This review gives a synopsis of CRPS and discusses the diagnosis, pathophysiology, and treatment options based on the limited evidence in the literature. PMID:22022040

  20. Is pain the price of empathy? The perception of others' pain in patients with congenital insensitivity to pain.

    PubMed

    Danziger, Nicolas; Prkachin, Kenneth M; Willer, Jean-Claude

    2006-09-01

    Empathy is a complex form of psychological inference that enables us to understand the personal experience of another person through cognitive/evaluative and affective processes. Recent findings suggest that empathy for pain may involve a 'mirror-matching' simulation of the affective and sensory features of others' pain. Despite such evidence for a shared representation of self and other pain at the neural level, the possible influence of the observer's own sensitivity to pain upon his perception of others' pain has not been investigated yet. The aim of this study was to explore how patients with congenital insensitivity to pain (CIP), who are largely deprived of common stimulus-induced pain experiences, perceive the pain of others. Ratings of verbally presented imaginary painful situations showed that CIP patients' semantic knowledge regarding the pain of others did not differ from control subjects. Moreover, the propensity to infer pain from facial expressions was very similar between CIP patients and control subjects. On the other hand, when asked to rate pain-inducing events seen in video clips in the absence of visible or audible pain-related behaviour, CIP patients showed more variable and significantly lower pain ratings, as well as a reduction in aversive emotional responses, compared with control subjects. Interestingly, pain judgements, inferred either from facial pain expressions or from pain-inducing events, were strongly related to inter-individual differences in emotional empathy among CIP patients, while such correlation between pain judgement and empathy was not found in control subjects. The results suggest that a normal personal experience of pain is not necessarily required for perceiving and feeling empathy for others' pain. In the absence of functional somatic resonance mechanisms shaped by previous pain experiences, others' pain might be greatly underestimated, however, especially when emotional cues are lacking, unless the observer is endowed

  1. Multidimensional Neuropathic Pain Phenotypes after Spinal Cord Injury.

    PubMed

    Widerström-Noga, Eva; Felix, Elizabeth R; Adcock, James P; Escalona, Maydelis; Tibbett, Jacqueline

    2016-03-01

    Identifying clinical neuropathic pain phenotypes is a first step to better understand the underlying pain mechanisms after spinal cord injury (SCI). The primary purpose of the present study was to characterize multidimensional neuropathic pain phenotypes based on quantitative sensory testing (QST), pain intensity, and utilization of catastrophizing coping strategies. Thermal perception, thermal pain, and vibratory perception thresholds were assessed above and below the level of injury (LOI) in 101 persons with SCI and neuropathic pain, 18 persons with SCI and no neuropathic pain, and 50 able-bodied, pain-free controls. Cluster analysis of QST z-scores below the LOI, pain intensity ratings, and the Coping Strategies Questionnaire (CSQ) catastrophizing subscale scores in subjects with neuropathic pain resulted in two phenotypes: severe neuropathic pain (SNP) with greater pain intensity (7.39 ± 1.57) and thermal and vibratory sensitivity compared with the moderate neuropathic pain (MNP; 5.40 ± 1.43). A factor analysis including all CSQ subscales, the Neuropathic Pain Symptom Inventory (NPSI) total score, and thermal pain sensitivity above and below the LOI resulted in three factors: (1) adaptive pain coping including increasing activities, diverting attention, and reinterpreting pain sensations; (2) catastrophizing, neuropathic pain, and thermal sensitivity including greater NPSI total score, thermal pain sensitivity below the LOI, and catastrophizing; and (3) general pain sensitivity including greater thermal pain sensitivity above the LOI and lower catastrophizing. Our results suggest that neuropathic pain symptom severity post-SCI is significantly associated with residual spinothalamic tract function below the LOI and catastrophizing pain coping.

  2. Laboratory testing for prescription opioids.

    PubMed

    Milone, Michael C

    2012-12-01

    Opioid analgesic misuse has risen significantly over the past two decades, and these drugs now represent the most commonly abused class of prescription medications. They are a major cause of poisoning deaths in the USA exceeding heroin and cocaine. Laboratory testing plays a role in the detection of opioid misuse and the evaluation of patients with opioid intoxication. Laboratories use both immunoassay and chromatographic methods (e.g., liquid chromatography with mass spectrometry detection), often in combination, to yield high detection sensitivity and drug specificity. Testing methods for opioids originated in the workplace-testing arena and focused on detection of illicit heroin use. Analysis for a wide range of opioids is now required in the context of the prescription opioid epidemic. Testing methods have also been primarily based upon urine screening; however, methods for analyzing alternative samples such as saliva, sweat, and hair are available. Application of testing to monitor prescription opioid drug therapy is an increasingly important use of drug testing, and this area of testing introduces new interpretative challenges. In particular, drug metabolism may transform one clinically available opioid into another. The sensitivity of testing methods also varies considerably across the spectrum of opioid drugs. An understanding of opioid metabolism and method sensitivity towards different opioid drugs is therefore essential to effective use of these tests. Improved testing algorithms and more research into the effective use of drug testing in the clinical setting, particularly in pain medicine and substance abuse, are needed.

  3. 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

  4. Depth-resolved simplified characterization of collagen depletion in dermis with polarization sensitive optical coherence tomography applicable to non-laboratory conditions

    NASA Astrophysics Data System (ADS)

    Tougbaev, Vitali; Eom, Tae Joong; Shin, Woojin; Lee, Yeung Lak; Yu, Bong-Ahn; Kee, Chul-Sik; Ko, Do-Kyeong; Lee, Jongmin

    2007-07-01

    A further insight into the prior concept of polarization sensitive optical coherence tomography system intended for non-laboratory conditions is brought forward and an experimental proof-of-concept is presented. A phenomenological model is adopted from the theory of light depolarization in crystalline polymers and modified to yield a simplified algorithm for mapping depolarization ratio in dermis. The algorithm could distinguish between dermal layers with depleted collagen content and normal dermis of normal perilesional skin. Dermis is simulated by bireringent lamellae of collagen arranged chaotically in multiple layers parallel to the skin surface. Both the design concept and the model imply the sub-millimeter tumor thickness as a proofed prognostic factor and an important criterion for complementary functional diagnostics of skin cancers at their early phase of vertical growth. Choice of the model is inspired by similarity of structural and optical properties between liquid-crystal collagen fibers in dermis and birefringent crystalline lamellae in polymer materials. The numerical computation based on the model allowing for real characteristics of dermis gives plausible interpreting of depolarization peculiarities caused by collagen depletion. Feasibility is discussed of exploiting fiber optic analogs of achromatic retarders. Fabrication of the fiber retarders is shown to be realistic by making use of the photonics technology possessed by the authors.

  5. 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.

  6. Low back pain - chronic

    MedlinePlus

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause of ...

  7. Sensitive skin.

    PubMed

    Misery, L; Loser, K; Ständer, S

    2016-02-01

    Sensitive skin is a clinical condition defined by the self-reported facial presence of different sensory perceptions, including tightness, stinging, burning, tingling, pain and pruritus. Sensitive skin may occur in individuals with normal skin, with skin barrier disturbance, or as a part of the symptoms associated with facial dermatoses such as rosacea, atopic dermatitis and psoriasis. Although experimental studies are still pending, the symptoms of sensitive skin suggest the involvement of cutaneous nerve fibres and neuronal, as well as epidermal, thermochannels. Many individuals with sensitive skin report worsening symptoms due to environmental factors. It is thought that this might be attributed to the thermochannel TRPV1, as it typically responds to exogenous, endogenous, physical and chemical stimuli. Barrier disruptions and immune mechanisms may also be involved. This review summarizes current knowledge on the epidemiology, potential mechanisms, clinics and therapy of sensitive skin.

  8. Neuropathic pain

    PubMed Central

    Colloca, Luana; Ludman, Taylor; Bouhassira, Didier; Baron, Ralf; Dickenson, Anthony H.; Yarnitsky, David; Freeman, Roy; Truini, Andrea; Attal, Nadine; Finnerup, Nanna B.; Eccleston, Christopher; Kalso, Eija; Bennett, David L.; Dworkin, Robert H.; Raja, Srinivasa N.

    2017-01-01

    Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7–10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain. PMID:28205574

  9. Managing Neuropathic Pain in Dogs

    PubMed Central

    Moore, Sarah A.

    2016-01-01

    Disorders of the somatosensory system such as neuropathic pain are common in people with chronic neurologic and musculoskeletal diseases, yet these conditions remain an underappreciated morbidity in veterinary patients. This is likely because assessment of neuropathic pain in people relies heavily on self-reporting, something our veterinary patients are not able to do. The development of neuropathic pain is a complex phenomenon, and concepts related to it are frequently not addressed in the standard veterinary medical curriculum such that veterinarians may not recognize this as a potential problem in patients. The goals of this review are to discuss basic concepts in the pathophysiology of neuropathic pain, provide definitions for common clinical terms used in association with the condition, and discuss pharmacological treatment options for dogs with neuropathic pain. The development of neuropathic pain involves key mechanisms such as ectopic afferent nerve activity, peripheral sensitization, central sensitization, impaired inhibitory modulation, and pathologic activation of microglia. Treatments aimed at reducing neuropathic pain are targeted at one or more of these mechanisms. Several drugs are commonly used in the veterinary clinical setting to treat neuropathic pain. These include gabapentin, pregabalin, amantadine, and amitriptyline. Proposed mechanisms of action for each drug, and known pharmacokinetic profiles in dogs are discussed. Strong evidence exists in the human literature for the utility of most of these treatments, but clinical veterinary-specific literature is currently limited. Future studies should focus on objective methods to document neuropathic pain and monitor response to therapy in veterinary patients. PMID:26942185

  10. Lifetime Modulation of the Pain System via Neuroimmune and Neuroendocrine Interactions

    PubMed Central

    Zouikr, Ihssane; Karshikoff, Bianka

    2017-01-01

    Chronic pain is a debilitating condition that still is challenging both clinicians and researchers. Despite intense research, it is still not clear why some individuals develop chronic pain while others do not or how to heal this disease. In this review, we argue for a multisystem approach to understand chronic pain. Pain is not only to be viewed simply as a result of aberrant neuronal activity but also as a result of adverse early-life experiences that impact an individual’s endocrine, immune, and nervous systems and changes which in turn program the pain system. First, we give an overview of the ontogeny of the central nervous system, endocrine, and immune systems and their windows of vulnerability. Thereafter, we summarize human and animal findings from our laboratories and others that point to an important role of the endocrine and immune systems in modulating pain sensitivity. Taking “early-life history” into account, together with the past and current immunological and endocrine status of chronic pain patients, is a necessary step to understand chronic pain pathophysiology and assist clinicians in tailoring the best therapeutic approach. PMID:28348566

  11. 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.

  12. Painful consequences of anger suppression.

    PubMed

    Quartana, Phillip J; Burns, John W

    2007-05-01

    The authors experimentally examined the effects of anger suppression on pain perception. On the basis of ironic process theory, they proposed that efforts to suppress experiential or expressive components of anger may paradoxically enhance cognitive accessibility of anger-related thoughts and feelings, thereby contaminating perception of succeeding pain in an anger-congruent manner. Participants were randomly assigned to nonsuppression or experiential or expressive suppression conditions during mental arithmetic with or without harassment. A cold-pressor task followed. Results revealed that participants instructed to suppress experiential or expressive components of emotion during harassment not only reported the greatest pain levels, but also rated the anger-specific dimensions of pain uniquely strong. Results suggest that attempts to suppress anger may amplify pain sensitivity by ironically augmenting perception of the irritating and frustrating qualities of pain.

  13. Assessment of pain: types, mechanism and treatment.

    PubMed

    Swieboda, Paulina; Filip, Rafał; Prystupa, Andrzej; Drozd, Mariola

    2013-01-01

    Pain is the most common symptom of disease, which accompanies us from an early age. It is a protective mechanism to which the body responds to harmful stimulus. The definition of pain states that it is a subjective sensory and emotional experience. It is connected to the stimulus that it invokes and is also based on the observation of psychological interpretation of the phenomena taking place. Pain is individual for each person. Pain affects both our previous experience of pain and psychosomatic conditions, depending on the relationship between the psyche and the body. Pain is always an unpleasant sensation. The feeling of pain can be caused by irritation of pain receptors, which can be found in the skin, joints and many internal organs. The cause of pain may also be damage to the nervous system, both the peripheral nerves, brain and spinal cord. Pain can also occur without damage to tissues, although the patient refers to it (psychogenic pain). The process of pain is a complex phenomenon. Experience of pain depends on the strength of the stimulus, individual susceptibility and individual resistance to pain. Pain receptors are sensitive to mechanical, thermal or chemical stimuli. The operation of noxious stimulus to these receptors results in the processing into an electrical signal. This impulse is conducted by nerve fibress into the spinal cord and then to the brain. At this point, there is the realization that something hurts us. Pain is not only somatic in nature, associated with the condition of the body, but it is a multidimensional phenomenon. Therefore, in addition to the physiological process of pain, its subjective perception is also important, which is decided by the central nervous system. It consists of the emotional aspects: suffering and attitude towards pain and pain expression. A review of pain physiology is essential to fully understand the principles of pain management.

  14. Painful diabetic neuropathy: clinical aspects.

    PubMed

    Didangelos, Triantafyllos; Doupis, John; Veves, Aristidis

    2014-01-01

    Painful diabetic neuropathy (PDN) is one of several clinical syndromes in patients with diabetic peripheral neuropathy (DPN) and presents a major challenge for optimal management. The epidemiology of PDN has not been extensively studied. On the basis of available data, the prevalence of pain ranges from 10% to 20% in patients with diabetes and from 40% to 50% in those with diabetic neuropathy. Neuropathic pain can be disabling and devastating, with a significant impact on the patient's quality of life and associated healthcare cost. Pathophysiologic mechanisms underlying PDN are similar to other neuropathic pain disorders and broadly invoke peripheral and central sensitization. The natural course of PDN is variable, with the majority of patients experiencing spontaneous improvement and resolution of pain. Quantifying neuropathic pain is difficult, especially in clinical practice, but has improved recently in clinical trials with the development of neuropathic pain-specific tools, such as the Neuropathic Pain Questionnaire and the Neuropathic Pain Symptom Inventory. Hyperglycemia-induced pathways result in nerve dysfunction and damage, which lead to hyperexcitable peripheral and central pathways of pain. Glycemic control may prevent or partially reverse DPN and modulate PDN.

  15. [Facial pain].

    PubMed

    Makhinov, K A; Barinov, A N; Zhestikova, M G; Mingazova, L R; Parkhomenko, E V

    2015-01-01

    Diagnosis and treatment of facial pain is a problem for physicians of different specialties (neurologists, dentists, surgeons, oculists, otolaryngologists and psychiatrists). A classification of this pathology is far from ideal and an interdisciplinary comprehensive approach is needed. Current approaches to etiotropic, symptomatic and pathogenetic treatment of patients with most frequent variants of orofacial pain are presented.

  16. [Heel pain].

    PubMed

    Cizmár, I; Svizenská, I; Pilný, J; Repko, M; Ira, D

    2005-01-01

    Heel pain is quite frequent clinical symptom in our population. Successful therapy derives from the problem aetiology. The most frequent source of pain is the mechanical basis, both on dorsal and plantar side of calcaneum. Therapy includes a variety of procedures, from routine measures to surgical intervention.

  17. Human pain and genetics: some basics

    PubMed Central

    2013-01-01

    Human pain causes untold misery and suffering, with major impact on functioning and resources. Recent advances in genetics have revealed that subtle changes in DNA could partly explain the variation in individual differences in pain. Various genes encoding for receptors are now known to play a major role in the sensitivity, perception and expression of pain. The fields of epigenetics and proteomics hold promises in the way pain could be treated and managed in future. PMID:26516521

  18. Development of a Laboratory Micron-Resolution X-ray Microprobe to Map Mineralogy and Trace Elements at PPM Sensitivity for Digital Rock, Magma, and Mining Applications

    NASA Astrophysics Data System (ADS)

    Yun, W.; Lewis, S.; Stripe, B.; Chen, S.; Reynolds, D.; Spink, I.; Lyon, A.

    2015-12-01

    We are developing a patent-pending x-ray microprobe with substantially unprecedented performance attributes: <5 μm spot on the sample (with 1 μm targeted), large working distances of >2 cm, narrow spectral bandwidth, and large x-ray flux. The outstanding performance is enabled by: (1) a revolutionary new type of high flux x-ray source designed to be >10X brighter than the brightest rotating anode x-ray source available; (2) an axially symmetric x-ray mirror lens with large solid angle collection and high focusing efficiency; and (3) a detector configuration that enables the collection of 10X more x-rays than current microXRF designs. The sensitivity will be ppm-scale, far surpassing charged particle analysis (e.g. EPMA and SEM-EDS), and >1000X throughput over the leading micro-XRFs. Despite the introduction of a number of laboratory microXRF systems in the past decade, the state-of-the-art has been limited primarily by low resolution (~30 μm) and low throughput. This is substantially attributable to a combination of low x-ray source brightness and poor performance x-ray optics. Here we present our initial results in removing the x-ray source bottleneck, in which we use a novel x-ray source using Fine Anode Array Source Technology (Sigray FAAST™). When coupled with our proprietary high efficiency x-ray mirror lens, the throughput achieved is comparable to that of many synchrotron microXRF beamlines. Potential applications of the x-ray microprobe include high throughput mapping of mineralogy at high resolution, including trace elements, such as rare earth metals, and deposits (e.g. siderite, clays), with ppm sensitivity, providing information for properties such as permeability and elastic/mechanical properties, and to provide compositional information for Digital Rock. Additional applications include those in which the limited penetration of electrons limits achieving adequate statistics, such as determining the concentration of precious minerals in mine

  19. Gustatory pleasure and pain. The offset of acute physical pain enhances responsiveness to taste.

    PubMed

    Bastian, Brock; Jetten, Jolanda; Hornsey, Matthew J

    2014-01-01

    The idea that pain may serve to produce pleasurable states has been noted by theorists and, more recently, substantiated by empirical findings. We explored the possibility that, beyond producing positive hedonic states, the offset of pain may serve to enhance the capacity for gustatory pleasure. Across three studies we examined whether pain offset may enhance responsiveness to taste. In Study 1 participants enjoyed chocolate more after the experience of pain compared to completing a similar but non-painful task. In Study 2, pain offset increased the perceived intensity of a range of tastes, both pleasant and unpleasant, indicating that the effects of pain offset are not limited to the processing of positive hedonic stimuli. In Study 3, pain offset increased sensitivity to different flavors. The findings suggest that the offset of acute pain increases awareness of, and therefore sensitivity to, gustatory input, thereby enhancing the capacity for gustatory pleasure.

  20. Gustatory pleasure and pain: The offset of acute physical pain enhances responsiveness to taste.

    PubMed

    Bastian, Brock; Jetten, Jolanda; Hornsey, Matthew J

    2013-10-25

    The idea that pain may serve to produce pleasurable states has been noted by theorists and, more recently, substantiated by empirical findings. We explored the possibility that, beyond producing positive hedonic states, the offset of pain may serve to enhance the capacity for gustatory pleasure. Across three studies we examined whether pain offset may enhance responsiveness to taste. In Study 1 participants enjoyed chocolate more after the experience of pain compared to completing a similar but non-painful task. In Study 2, pain offset increased the perceived intensity of a range of tastes, both pleasant and unpleasant, indicating that the effects of pain offset are not limited to the processing of positive hedonic stimuli. In Study 3, pain offset increased sensitivity to different flavors. The findings suggest that the offset of acute pain increases awareness of, and therefore sensitivity to, gustatory input, thereby enhancing the capacity for gustatory pleasure.

  1. 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.

  2. Conceptual Uncertainty and Parameter Sensitivity in Subsurface Pathway Flow and Transport Modeling for the Idaho National Engineering and Environmental Laboratory's Subsurface Disposal Area

    NASA Astrophysics Data System (ADS)

    Magnuson, S. O.

    2002-05-01

    As part of an ongoing CERCLA evaluation, the migration of contaminants through the hydrologically complex subsurface at the Idaho National Engineering and Environmental Laboratory Subsurface Disposal Area (SDA) were modeled. The 180-meter thick vadose zone beneath the SDA is primarily composed of extrusive basalt flows that are extensively fractured. These flows are interrupted by thin, mostly continuous sedimentary interbeds that were deposited through aeolian and fluvial processes during periods of volcanic quiescence. The subsurface pathway modeling for the CERCLA assessment has been conducted in phases utilizing the results of characterization activities. The most recent model for the SDA used an equivalent porous continuum approach in a three-dimensional domain to represent movement of water and contaminants in the subsurface. Given the complexity of the subsurface at this site, the simulation results were acknowledged to be uncertain. This presentation will provide an overview of the current modeling effort for the SDA and how conceptual uncertainty was addressed by modeling different scenarios. These scenarios included assignment of infiltration boundary conditions, the effect of superimposing gaps in the interbeds, including the effect within the vadose zone from Big Lost River water discharged to the spreading areas approximately 1 km away, and a simplistic approximation to represent facilitated transport. Parametric sensitivity simulations were used to determine possible effects from assigned transport parameters such as partition coefficients and solubility limits that can vary widely with presumed geochemical conditions. Comparisons of simulated transport results to measured field concentrations in both the vadose zone and in the underlying Snake River Plain aquifer were made to determine the representativeness of the model results. Results of the SDA subsurface transport modeling have been used in part to guide additional field characterization

  3. Comparison of operant escape and reflex tests of nociceptive sensitivity.

    PubMed

    Vierck, Charles J; Yezierski, Robert P

    2015-04-01

    Testing of reflexes such as flexion/withdrawal or licking/guarding is well established as the standard for evaluating nociceptive sensitivity and its modulation in preclinical investigations of laboratory animals. Concerns about this approach have been dismissed for practical reasons - reflex testing requires no training of the animals; it is simple to instrument; and responses are characterized by observers as latencies or thresholds for evocation. In order to evaluate this method, the present review summarizes a series of experiments in which reflex and operant escape responding are compared in normal animals and following surgical models of neuropathic pain or pharmacological intervention for pain. Particular attention is paid to relationships between reflex and escape responding and information on the pain sensitivity of normal human subjects or patients with pain. Numerous disparities between results for reflex and operant escape measures are described, but the results of operant testing are consistent with evidence from humans. Objective reasons are given for experimenters to choose between these and other methods of evaluating the nociceptive sensitivity of laboratory animals.

  4. Fever with intradialytic pelvic pain: a case of iliopsoas abscess complicated with Methicillin-sensitive Staphylococcus Aureus bacteraemia in an end stage renal failure patient.

    PubMed

    Alif Adlan, M T; Wan Mohd Rasis, W A K; Mohd Ramadhan, M D

    2016-04-01

    Staphylococcus Aureus is a Gram-positive cocci bacteria which had been found to be the causative organism in over 88% of patients with primary iliopsoas abscess. We report the case of a 53-year-old diabetic woman with end-stage renal failure diagnosed with left iliopsoas abscess with a catheter-related infection. Computed tomogram (CT) of abdomen and pelvis revealed hypodense lesions of left psoas, iliacus and quadratus lumborum suggestive of psoas abscesses. In addition, osteomyelitis changes at left sacroiliac and hip joint were seen. At surgery, she was found to have abscess at the posterior psoas muscle where she underwent open surgery drainage and percutaneous drain was inserted. A high index of suspicion of iliopsoas abscess should be maintained among haemodialysis patients presenting with intradialytic pelvic and hip pain and treated with optimal antibiotics therapy with appropriate surgical intervention.

  5. Suprathreshold Heat Pain Response Predicts Activity-Related Pain, but Not Rest-Related Pain, in an Exercise-Induced Injury Model

    PubMed Central

    Coronado, Rogelio A.; Simon, Corey B.; Valencia, Carolina; Parr, Jeffrey J.; Borsa, Paul A.; George, Steven Z.

    2014-01-01

    Exercise-induced injury models are advantageous for studying pain since the onset of pain is controlled and both pre-injury and post-injury factors can be utilized as explanatory variables or predictors. In these studies, rest-related pain is often considered the primary dependent variable or outcome, as opposed to a measure of activity-related pain. Additionally, few studies include pain sensitivity measures as predictors. In this study, we examined the influence of pre-injury and post-injury factors, including pain sensitivity, for induced rest and activity-related pain following exercise induced muscle injury. The overall goal of this investigation was to determine if there were convergent or divergent predictors of rest and activity-related pain. One hundred forty-three participants provided demographic, psychological, and pain sensitivity information and underwent a standard fatigue trial of resistance exercise to induce injury of the dominant shoulder. Pain at rest and during active and resisted shoulder motion were measured at 48- and 96-hours post-injury. Separate hierarchical models were generated for assessing the influence of pre-injury and post-injury factors on 48- and 96-hour rest-related and activity-related pain. Overall, we did not find a universal predictor of pain across all models. However, pre-injury and post-injury suprathreshold heat pain response (SHPR), a pain sensitivity measure, was a consistent predictor of activity-related pain, even after controlling for known psychological factors. These results suggest there is differential prediction of pain. A measure of pain sensitivity such as SHPR appears more influential for activity-related pain, but not rest-related pain, and may reflect different underlying processes involved during pain appraisal. PMID:25265560

  6. Fetal pain?

    PubMed

    Vanhatalo, S; van Nieuwenhuizen, O

    2000-05-01

    During the last few years a vivid debate, both scientifically and emotionally, has risen in the medical literature as to whether a fetus is able to feel pain during abortion or intrauterine surgery. This debate has mainly been inspired by the demonstration of various hormonal or motor reactions to noxious stimuli at very early stages of fetal development. The aims of this paper are to review the literature on development of the pain system in the fetus, and to speculate about the relationship between "sensing" as opposed to "feeling" pain and the number of reactions associated with painful stimuli. While a cortical processing of pain theoretically becomes possible after development of the thalamo-cortical connections in the 26th week of gestation, noxious stimuli may trigger complex reflex reactions much earlier. However, more important than possible painfulness is the fact that the noxious stimuli, by triggering stress responses, most likely affect the development of an individual at very early stages. Hence, it is not reasonable to speculate on the possible emotional experiences of pain in fetuses or premature babies. A clinically relevant aim is rather to avoid and/or treat any possibly noxious stimuli, and thereby prevent their potential adverse effects on the subsequent development.

  7. Personality and Temperament Correlates of Pain Catastrophizing in Young Adolescents

    ERIC Educational Resources Information Center

    Muris, Peter; Meesters, Cor; van den Hout, Anja; Wessels, Sylvia; Franken, Ingmar; Rassin, Eric

    2007-01-01

    Pain catastrophizing is generally viewed as an important cognitive factor underlying chronic pain. The present study examined personality and temperament correlates of pain catastrophizing in a sample of young adolescents (N = 132). Participants completed the Pain Catastrophizing Scale for Children, as well as scales for measuring sensitivity of…

  8. What a Pain! Kids and Growing Pains

    MedlinePlus

    ... What Happens in the Operating Room? What a Pain! Kids and Growing Pains KidsHealth > For Kids > What a Pain! Kids and ... something doctors call growing pains . What Are Growing Pains? Growing pains aren't a disease. You probably ...

  9. What a Pain! Kids and Growing Pains

    MedlinePlus

    ... dientes Video: Getting an X-ray What a Pain! Kids and Growing Pains KidsHealth > For Kids > What a Pain! Kids and ... something doctors call growing pains . What Are Growing Pains? Growing pains aren't a disease. You probably ...

  10. Ocular neuropathic pain

    PubMed Central

    Rosenthal, Perry; Borsook, David

    2016-01-01

    As the biological alarm of impending or actual tissue damage, pain is essential for our survival. However, when it is initiated and/or sustained by dysfunctional elements in the nociceptive system, it is itself a disease known as neuropathic pain. While the critical nociceptive system provides a number of protective functions, it is unique in its central role of monitoring, preserving and restoring the optical tear film in the face of evaporative attrition without which our vision would be non-functional. Meeting this existential need resulted in the evolution of the highly complex, powerful and sensitive dry eye alarm system integrated in the peripheral and central trigeminal sensory network. The clinical consequences of corneal damage to these nociceptive pathways are determined by the type and location of its pathological elements and can range from the spectrum known as dry eye disease to the centalised oculofacial neuropathic pain syndrome characterised by a striking disparity between the high intensity of symptoms and paucity of external signs. These changes parallel those observed in somatic neuropathic pain. When seen through the neuroscience lens, diseases responsible for inadequately explained chronic eye pain (including those described as dry eye) can take on new meanings that may clarify long-standing enigmas and point to new approaches for developing preventive, symptomatic and disease-modifying interventions for these currently refractory disorders. PMID:25943558

  11. Chronic Pelvic Pain

    MedlinePlus

    ... Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  12. Chronic pain - resources

    MedlinePlus

    Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association -- theacpa.org National Fibromyalgia and Chronic Pain Association -- www.fmcpaware.org National ...

  13. Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

    DTIC Science & Technology

    2013-10-01

    elicits a number of changes in the activity, properties and transmitter content of pain -pathway neurons2. This central sensitization to nociceptive ...AD______ Award Number: W81XHW-11-1-0806 TITLE: Chronic pain following spinal cord injury. The...role of immunogenetics and time of injury pain treatment. PRINCIPAL INVESTIGATOR: Dr. Mark Hutchinson CONTRACTING ORGANIZATION: The

  14. Pain Management

    MedlinePlus

    ... analgesia, identify new targets for analgesic drugs, and test the efficacy and adverse reactions of newly developed or currently used drugs to treat pain. Researchers are currently using these technologies to discover the mechanisms by which drugs such ...

  15. Urination - painful

    MedlinePlus

    ... and vagina Other causes of painful urination include: Interstitial cystitis Prostate infection ( prostatitis ) Radiation cystitis - damage to the ... Editorial team. Related MedlinePlus Health Topics Bladder ... Cystitis Prostate Diseases Sexually Transmitted Diseases Urinary Tract Infections ...

  16. Joint pain

    MedlinePlus

    ... that may be done include: CBC or blood differential C-reactive protein Joint x-ray Sedimentation rate ... chap 256. Schaible H-G. Joint pain: basic mechanisms. In: McMahon SB, Koltzenburg M, Tracey I, Turk ...

  17. Testicle pain

    MedlinePlus

    ... be caused by a hernia or kidney stone. Testicular cancer is almost always painless. But any testicle lump ... Read More Abdominal pain Scrotum Testes Testicle lump Testicular cancer Testicular torsion Review Date 8/31/2015 Updated ...

  18. Chest Pain

    MedlinePlus

    ... causes Chest pain can also be caused by: Panic attack. If you have periods of intense fear accompanied ... fear of dying, you may be experiencing a panic attack. Shingles. Caused by a reactivation of the chickenpox ...

  19. Chronic Pain

    MedlinePlus

    ... Strategy Current Research Research Funded by NINDS Basic Neuroscience Clinical Research Translational Research Research at NINDS Focus ... pain has done. Scientists believe that advances in neuroscience will lead to more and better treatments for ...

  20. [Abdominal pain].

    PubMed

    Gschossmann, J M; Holtmann, G; Netzer, P; Essig, M; Balsiger, B M; Scheurer, U

    2005-10-01

    Abdominal pain can result from a variety of different intra- and extra-abdominal disorders. Given the wide variety of etiological triggers for this pain, the primary task during the first stage of the diagnostic work-up is to determine as soon as possible the underlying cause and the degree of emergency. The aim of this evaluation is to adapt the therapeutic measures which are necessary for a causal treatment to the individual situation. Contrary to somatic causes of abdominal pain, the availability of such a causal therapy for functional bowel disorders is still very limited. Given this dilemma, the therapeutic focus of abdominal pain associated with these functional syndromes has to be placed on symptom-oriented treatment.

  1. Fetal pain.

    PubMed

    Rokyta, Richard

    2008-12-01

    The fetus reacts to nociceptive stimulations through different motor, autonomic, vegetative, hormonal, and metabolic changes relatively early in the gestation period. With respect to the fact that the modulatory system does not yet exist, the first reactions are purely reflexive and without connection to the type of stimulus. While the fetal nervous system is able to react through protective reflexes to potentially harmful stimuli, there is no accurate evidence concerning pain sensations in this early period. Cortical processes occur only after thalamocortical connections and pathways have been completed at the 26th gestational week. Harmful (painful) stimuli, especially in fetuses have an adverse effect on the development of humans regardless of the processes in brain. Moreover, pain activates a number of subcortical mechanisms and a wide spectrum of stress responses influence the maturation of thalamocortical pathways and other cortical activation which are very important in pain processing.

  2. Breast pain

    MedlinePlus

    ... chocolate in your diet helps reduce breast pain. Vitamin E, thiamine, magnesium, and evening primrose oil are not harmful, but most studies have not shown any benefit. Talk to your health care provider before starting ...

  3. Reduced Cold Pain Tolerance in Chronic Pain Patients Following Opioid Detoxification

    PubMed Central

    Younger, Jarred; Barelka, Peter; Carroll, Ian; Kaplan, Kim; Chu, Larry; Prasad, Ravi; Gaeta, Ray; Mackey, Sean

    2009-01-01

    Objective One potential consequence of chronic opioid analgesic administration is a paradoxical increase of pain sensitivity over time. Little scientific attention has been given to how cessation of opioid medication affects the hyperalgesic state. In this study, we examined the effects of opioid tapering on pain sensitivity in chronic pain patients. Design Twelve chronic pain patients on long-term opioid analgesic treatment were observed in a 7- to 14-day inpatient pain rehabilitation program, with cold pain tolerance assessed at admission and discharge. The majority of participants were completely withdrawn from their opioids during their stay. Outcome Measures We hypothesized that those patients with the greatest reduction in daily opioid use would show the greatest increases in pain tolerance, as assessed by a cold pressor task. Results A linear regression revealed that the amount of opioid medication withdrawn was a significant predictor of pain tolerance changes, but not in the direction hypothesized. Greater opioid reduction was associated with decreased pain tolerance. This reduction of pain tolerance was not associated with opioid withdrawal symptoms or changes in general pain. Conclusions These findings suggest that the withdrawal of opioids in a chronic pain sample leads to an acute increase in pain sensitivity. PMID:18564998

  4. 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

  5. Disposition and adjustment to chronic pain.

    PubMed

    Ramírez-Maestre, Carmen; Esteve, Rosa

    2013-03-01

    Several empirical studies have shown that personal characteristics act as differential variables, which determine how pain is experienced and how the chronic pain patient adjusts to pain. The main aim of the present research is to review the relationships between some dispositional characteristics and pain adjustment. Taking into account the empirical literature, 6 personality traits that are relevant to the pain experience have been selected: neuroticism, anxiety sensitivity, and experiential avoidance as risk factors that increase the probability of patients experiencing a disability; and extraversion, optimism, and resilience as personal resources that increase their capacity to manage pain effectively. The results suggest that it would be useful to include an assessment of normal personality structure during the multi-dimensional evaluation of a person with chronic pain. Understanding these individual personality characteristics will aid in designing pain intervention programs and help predict possible treatment outcomes.

  6. 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

  7. "Imprisoned" in pain: analyzing personal experiences of phantom pain.

    PubMed

    Nortvedt, Finn; Engelsrud, Gunn

    2014-11-01

    This article explores the phenomenon of "phantom pain." The analysis is based on personal experiences elicited from individuals who have lost a limb or live with a paralyzed body part. Our study reveals that the ways in which these individuals express their pain experience is an integral aspect of that experience. The material consists of interviews undertaken with men who are living with phantom pain resulting from a traumatic injury. The phenomenological analysis is inspired by Zahavi (J Conscious Stud 8(5-7):151-167, 2001) and Merleau-Ponty (Phenomenology of perception. Routledge and Kegan Paul, London, 1962/2000). On a descriptive level the metaphors these patients invoke to describe their condition reveal immense suffering, such as a feeling of being invaded by insects or of their skin being scorched and stripped from their body. Such metaphors express a dimension of experience concerning the self that is in pain and others whom the sufferer relates to through this pain, as well as the agony that this pain inflicts in the world of lived experience. This pain has had a profound impact on their lives and altered their relationship with self (body), others and the world. Their phantom pain has become a reminder of their formerly intact and functioning body; they describe the contrast between their past and present body as an ambiguous and disturbing experience. We conclude that these sensitive and personalized experiences of phantom pain illuminates how acts of expression--spoken pain--constitute a fundamental dimension of a first-person perspective which contribute to the field of knowledge about "phantom pain".

  8. Kaurenoic acid from Sphagneticola trilobata Inhibits Inflammatory Pain: effect on cytokine production and activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway.

    PubMed

    Mizokami, Sandra S; Arakawa, Nilton S; Ambrosio, Sergio R; Zarpelon, Ana C; Casagrande, Rubia; Cunha, Thiago M; Ferreira, Sergio H; Cunha, Fernando Q; Verri, Waldiceu A

    2012-05-25

    Kaurenoic acid [ent-kaur-16-en-19-oic acid (1)] is a diterpene present in several plants including Sphagneticola trilobata. The only documented evidence for its antinociceptive effect is that it inhibits the writhing response induced by acetic acid in mice. Therefore, the analgesic effect of 1 in different models of pain and its mechanisms in mice were investigated further. Intraperitoneal and oral treatment with 1 dose-dependently inhibited inflammatory nociception induced by acetic acid. Oral treatment with 1 also inhibited overt nociception-like behavior induced by phenyl-p-benzoquinone, complete Freund's adjuvant (CFA), and both phases of the formalin test. Compound 1 also inhibited acute carrageenin- and PGE(2)-induced and chronic CFA-induced inflammatory mechanical hyperalgesia. Mechanistically, 1 inhibited the production of the hyperalgesic cytokines TNF-α and IL-1β. Furthermore, the analgesic effect of 1 was inhibited by l-NAME, ODQ, KT5823, and glybenclamide treatment, demonstrating that such activity also depends on activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway, respectively. These results demonstrate that 1 exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of cytokine production and activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway.

  9. The predictive value of attentional bias towards pain-related information in chronic pain patients: a diary study.

    PubMed

    Van Ryckeghem, Dimitri M L; Crombez, Geert; Goubert, Liesbet; De Houwer, Jan; Onraedt, Thomas; Van Damme, Stefaan

    2013-03-01

    Theoretical accounts of chronic pain hypothesize that attentional bias towards pain-related information is a maintaining or exacerbating factor, fuelling further pain, disability, and distress. However, empirical research testing this idea is currently lacking. In the present study, we investigated whether attentional bias towards pain-related information predicts daily pain-related outcomes in a sample of chronic pain patients (n=69; M(age)=49.64 years; 46 females). During an initial laboratory session, attentional bias to pain-related information was assessed using a modified spatial cueing task. In advance, patients completed a number of self-report measures assessing current pain intensity, current disability, and pain duration. Subsequently, daily pain outcomes (self-reported pain severity, disability, avoidance behaviour, and distractibility) were measured for 2 weeks by means of an electronic diary. Results indicated that, although an attentional bias towards pain-related information was associated with the current level of disability and pain severity, it had no additional value above control variables in predicting daily pain severity, avoidance, distractibility, and disability. Attentional bias towards pain-related information did, however, moderate the relationship between daily pain severity and both daily disability and distractibility, indicating that, particularly in those patients with a strong attentional bias, increases in pain were associated with increased disability and distractibility. The use of interventions that diminish attentional bias may therefore be helpful to reduce daily disability and the level of distraction from current tasks despite the presence of pain in chronic pain patients.

  10. Low back pain - acute

    MedlinePlus

    Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back strain - new ... lower back supports most of your body's weight. Low back pain is the number two reason that Americans see ...

  11. Accounting for the Association Between BPD Features and Chronic Pain Complaints in a Pain Patient Sample: The Role of Emotion Dysregulation Factors.

    PubMed

    Reynolds, Caleb J; Carpenter, Ryan W; Tragesser, Sarah L

    2017-02-16

    Although borderline personality disorder (BPD) features consistently show strong relations with chronic pain, the mechanisms underlying this association remain unclear. BPD is characterized by dysregulated emotion. Given previously observed relationships between emotion dysregulation and pain, we hypothesized that components of this dysregulation-elevated and labile negative affect and emotion sensitivity-would account for the relationship between BPD features and various pain complaints in a chronic pain patient sample. Specifically, we hypothesized that negative affect would indirectly predict pain through higher emotion sensitivity to pain, operationalized as pain anxiety sensitivity. To test these hypotheses, we administered a series of self-report measures to 147 patients at a chronic pain treatment facility. As expected, BPD features predicted pain severity (β = .19, p = .029), activity interference from pain (β = .22, p = .015), and affective interference from pain (β = .41, p < .001). Using path analyses, we found that the associations between BPD features and pain severity and interference were accounted for by serial indirect pathways through affective lability then pain anxiety and, to a lesser extent, through trait anxiety then pain anxiety. This is the first study to demonstrate roles for affective lability and pain anxiety sensitivity in the association between BPD features and chronic pain complaints in a chronic pain sample. We discuss implications for the relationship between dysregulated emotion and pain as well as for psychologically-focused treatment interventions for pain. (PsycINFO Database Record

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

    PubMed Central

    Sturgeon, John A.; Johnson, Kevin A.

    2017-01-01

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

  13. The Antinociceptive Effect of a Tapentadol-Ketorolac Combination in a Mouse Model of Trigeminal Pain is Mediated by Opioid Receptors and ATP-Sensitive K(+) Channels.

    PubMed

    Barreras-Espinoza, Israel; Soto-Zambrano, José Alberto; Serafín-Higuera, Nicolás; Zapata-Morales, Ramón; Alonso-Castro, Ángel; Bologna-Molina, Ronell; Granados-Soto, Vinicio; Isiordia-Espinoza, Mario A

    2017-02-01

    Preclinical Research The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED50 values and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs. The combination showed antinociceptive synergistic and additive effects in the first and second phase of the orofacial formalin test. Naloxone and glibenclamide were used to evaluate the possible mechanisms of action and both partially reversed the antinociception produced by the tapentadol-ketorolac combination. These data suggest that the mixture of tapentadol and ketorolac produces additive or synergistic interactions via opioid receptors and ATP-sensitive K(+) channels in the orofacial formalin-induced nociception model in mice. Drug Dev Res 78 : 63-70, 2017. © 2016 Wiley Periodicals, Inc.

  14. Sensitivity and specificity of simultaneously acquired (dual channel) radiogallium and Tc-99m-HDP in painful hip and knee prosthetic joints

    SciTech Connect

    Skarzynski, J.J.; Sziklas, J.J.; Rosenberg, R.J.; Rich, D.A.; Spencer, R.P.

    1985-05-01

    Differentiation of prosthetic loosening from infection, by use of sequential bone and radiogallium imaging, has been discussed in the literature. The authors investigated simultaneous (2 channel) imaging of Ga-67 and Tc-99m-HDP in multiviews, in order to assess the parameter of Tc-99m-Ga-67 incongruity. Acquisition of data was carried out 2 days after 5 mCi of Ga-67 citrate IV and 2 hours after 8 mCi of Tc-99m-HDP. Dual data channels were used to insure perfect superimposition of the images and to reduce total imaging time. Normalized bone images were taken, then subtracted from those of Ga-67, by means of progressive weighting factors. A total of 68 studies were carried out on 43 patients. Exams involved both knee and hip prostheses, in population with 63% of the patients over age 60 years. Time from placement of the prosthesis to the dual radionuclide exam was within 2 years in 48% and within 5 years in 78%. Sensitivity was 0.88 and specificity 0.89. Using information on the follow-up dual channel studies, 40/43 cases were correctly identified (93%). Dual channel radionuclide imaging offers a readily available and accurate means of differentiating infection from loosening of hip or knee prostheses.

  15. Distribution of Spinal Sensitization Evoked by Inflammatory Pain Using Local Spinal Cord Glucose Utilization Combined with (3) H-Phorbol 12,13-Dibutyrate Binding in Rats.

    PubMed

    Seiko, Yasuda; Kozo, Ishikawa; Yoshihiro, Matsumoto; Toru, Ariyoshi; Hironori, Sasaki; Yuika, Ida; Yasutake, Iwanaga; Hae-Kyu, Kim; Osamu, Nakanishi; Toshizo, Ishikawa

    2013-01-01

    Aims. Hyperalgesia following tissue injury is induced by plasticity in neurotransmission. Few investigators have considered the ascending input which activates the superficial of spinal cord. The aim was to examine neurotransmission and nociceptive processing in the spinal cord after mustard-oil (MO) injection. Both in vitro and in vivo autoradiographs were employed for neuronal activity and transmission in discrete spinal cord regions using the (14)C-2-deoxyglucose method and (3)H-phorbol 12,13-dibutyrate ((3)H-PDBu) binding sites. Methods. To quantify the hyperalgesia evoked by MO, the flinching was counted for 60 min after MO (20%, 50 μL) injection in Wistar rats. Simultaneous determination of (14)C-2-deoxyglucose and (3)H-PDBu binding was used for a direct observation of neuronal/metabolic changes and intracellular signaling in the spinal cord. Results. MO injection evoked an increase in flinching for 60 min. LSCGU significantly increased in the Rexed I-II with (3)H-PDBu binding in the ipsilateral side of spinal cord. Discussion. We clearly demonstrated that the hyperalgesia is primarily relevant to increased neuronal activation with PKC activation in the Rexed I-II of the spinal cord. In addition, functional changes such as "neuronal plasticity" may result in increased neuronal excitability and a central sensitization.

  16. Distribution of Spinal Sensitization Evoked by Inflammatory Pain Using Local Spinal Cord Glucose Utilization Combined with 3H-Phorbol 12,13-Dibutyrate Binding in Rats

    PubMed Central

    Seiko, Yasuda; Kozo, Ishikawa; Yoshihiro, Matsumoto; Toru, Ariyoshi; Hironori, Sasaki; Yuika, Ida; Yasutake, Iwanaga; Hae-Kyu, Kim; Osamu, Nakanishi; Toshizo, Ishikawa

    2013-01-01

    Aims. Hyperalgesia following tissue injury is induced by plasticity in neurotransmission. Few investigators have considered the ascending input which activates the superficial of spinal cord. The aim was to examine neurotransmission and nociceptive processing in the spinal cord after mustard-oil (MO) injection. Both in vitro and in vivo autoradiographs were employed for neuronal activity and transmission in discrete spinal cord regions using the 14C-2-deoxyglucose method and 3H-phorbol 12,13-dibutyrate (3H-PDBu) binding sites. Methods. To quantify the hyperalgesia evoked by MO, the flinching was counted for 60 min after MO (20%, 50 μL) injection in Wistar rats. Simultaneous determination of 14C-2-deoxyglucose and 3H-PDBu binding was used for a direct observation of neuronal/metabolic changes and intracellular signaling in the spinal cord. Results. MO injection evoked an increase in flinching for 60 min. LSCGU significantly increased in the Rexed I-II with 3H-PDBu binding in the ipsilateral side of spinal cord. Discussion. We clearly demonstrated that the hyperalgesia is primarily relevant to increased neuronal activation with PKC activation in the Rexed I-II of the spinal cord. In addition, functional changes such as “neuronal plasticity” may result in increased neuronal excitability and a central sensitization. PMID:27335874

  17. Pain characteristics in fibromyalgia: understanding the multiple dimensions of pain.

    PubMed

    Plazier, Mark; Ost, Jan; Stassijns, Gaëtane; De Ridder, Dirk; Vanneste, Sven

    2015-04-01

    Fibromyalgia is a common disease with a high economic burden. The etiology of this disease remains unclear, as there are no specific abnormalities on clinical or technical examinations. Evidence suggests that central pain sensitization at the brain pain matrix might be involved. Understanding the pain characteristics of this disease is of importance both for diagnosis and treatment. The authors present their findings of pain characteristics in a Belgium population of fibromyalgia patients. Data of 65 patients (57 male and 8 female patients) were analyzed in this study (mean age 46.86, SD = +8.79). Patients filled out the following questionnaires: visual analogue scale, fibromyalgia impact questionnaire, pain-catastrophizing scale, pain vigilance and awareness questionnaire, modified fatigue impact scale, the Beck depression inventory, the short form 36 and the Dutch shortened profile of mood states. Statistical analysis was performed making use of a factor analysis and a hierarchical cluster analysis. We were able to define pain characteristics in this group of patients. The reciprocal effects of mood and fatigue on pain experience could be identified within the data, catastrophizing scores show a high correlation with overall life quality and pain experience. We have performed a cluster analysis on the fibromyalgia patients, based on the four main principal components defining the overall disease burden. Mood explained most of the variance in symptoms, followed by mental health state, fatigue, and catastrophizing. Three clusters of patients could be revealed by these components. Clusters: 1 high scores on mood disorders, pain, and decreased mental health, 2 high scores on fatigue and physical health, and 3 a mixture of these two groups. This data suggest that different subgroups of fibromyalgia patients could be identified and based on that, treatment strategies and results might be adapted.

  18. Maternal family history of hypertension attenuates neonatal pain response.

    PubMed

    France, Christopher R; Taddio, Anna; Shah, Vibhuti S; Pagé, M Gabrielle; Katz, Joel

    2009-04-01

    Reduced sensitivity to naturally occurring and laboratory pain stimuli has been observed in individuals with hypertension, high-normal blood pressure, and a family history of hypertension. The present study sought to extend these findings by examining the relationship between familial history of hypertension and pain responsivity in neonates. Eighty infants had intramuscular (IM) injections of vitamin K performed in the delivery room within 1h of birth as per institutional practice. Video recordings of the injection procedure were used by trained observers to code infant pain responses using facial grimacing and cry duration. Prior to the birth of the child, the infants' parents each completed a family blood pressure history survey and these responses were used to identify infants with and without a maternal and paternal family history of hypertension. As compared to infants without a maternal family history of hypertension, infants with a maternal family history of hypertension had significantly shorter crying times, F(1,74)=6.96, p=.01, eta(2)=.086, and marginally lower facial grimacing scores, F(1,74)=2.68, p=.10, eta(2)=.035, during vitamin K injection. The presence of attenuated responses to the IM injection in neonates with a maternal family history of hypertension provides important and novel evidence that reduced pain responding in individuals at risk for hypertension is not a learned response style, but rather may arise from prenatal or genetic influences.

  19. Abdominal Pain

    MedlinePlus

    ... call your doctor. In Spanish— Dolor abdominal en niños menores de 12 años What is recurrent abdominal ... Functional abdominal pain (FAP) typically affects kids ages 4-12, and is quite common, affecting up to ...

  20. [Elbow pain].

    PubMed

    Viikari-Juntura, Eira; Miintyselkii, Pekka; Havulinna, Jouni

    2010-01-01

    Pain and disability in the elbow are not as common as in the neck, shoulder or wrist, for example. The elbow may, however, present disorders that may in a prolonged state be difficult and cause significant loss of working capacity. These include epicondylitis, osteoarthritis and entrapment of the ulnar nerve.

  1. Achilles Pain.

    ERIC Educational Resources Information Center

    Connors, G. Patrick

    Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…

  2. Neck pain

    MedlinePlus

    ... neck. If neck pain involves compression of your nerves, you may feel numbness, tingling, or weakness in your arm or ... When to Contact a Medical Professional ... fever and headache, and your neck is so stiff that you cannot touch your chin to your chest. This may be ...

  3. Experimental pain phenotyping in community-dwelling individuals with knee osteoarthritis.

    PubMed

    Cardoso, Josue S; Riley, Joseph L; Glover, Toni; Sibille, Kimberly T; Bartley, Emily J; Goodin, Burel R; Bulls, Hailey W; Herbert, Matthew; Addison, Adriana S; Staud, Roland; Redden, David T; Bradley, Laurence A; Fillingim, Roger B; Cruz-Almeida, Yenisel

    2016-09-01

    Pain among individuals with knee osteoarthritis (OA) is associated with significant disability in older adults, and recent evidence demonstrates enhanced experimental pain sensitivity. Although previous research showed considerable heterogeneity in the OA clinical pain presentation, less is known regarding the variability in responses to experimental pain. The present study included individuals with knee OA (n = 292) who participated in the Understanding Pain and Limitations in Osteoarthritic Disease study and completed demographic and psychological questionnaires followed by a multimodal quantitative sensory testing (QST) session. Quantitative sensory testing measures were subjected to variable reduction procedures to derive pain sensitivity index scores, which in turn were entered into a cluster analysis. Five clusters were significantly different across all pain sensitivity index variables (P < 0.001) and were characterized by: (1) low pain sensitivity to pressure pain (N = 39); (2) average pain sensitivity across most modalities (N = 88); (3) high temporal summation of punctate pain (N = 38); (4) high cold pain sensitivity (N = 80); and (5) high sensitivity to heat pain and temporal summation of heat pain (N = 41). Clusters differed significantly by race, gender, somatic reactivity, and catastrophizing (P < 0.05). Our findings support the notion that there are distinct subgroups or phenotypes based on experimental pain sensitivity in community-dwelling older adults with knee OA, expanding previous findings of similar cluster characterizations in healthy adults. Future research is needed to further understand the pathophysiological mechanisms underlying pain within these subgroups, which may be of added value in tailoring effective treatments for people with OA.

  4. Employees with Chronic Pain

    MedlinePlus

    ... Home | Accommodation and Compliance Series: Employees with Chronic Pain By Beth Loy, Ph.D. Preface Introduction Information ... at http://AskJAN.org/soar. Information about Chronic Pain How prevalent is chronic pain? Chronic pain has ...

  5. When Sex Is Painful

    MedlinePlus

    ... AQ FREQUENTLY ASKED QUESTIONS GYNECOLOGIC PROBLEMS FAQ020 When Sex Is Painful • How common is painful sex? • What causes pain during sex? • Where is pain during sex felt? • When should ...

  6. Acute sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to copper, cadmium, or zinc in water-only laboratory exposures.

    PubMed

    Calfee, Robin D; Little, Edward E; Puglis, Holly J; Scott, Erinn; Brumbaugh, William G; Mebane, Christopher A

    2014-10-01

    The acute toxicity of cadmium, copper, and zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) were determined for 7 developmental life stages in flow-through water-only exposures. Metal toxicity varied by species and by life stage. Rainbow trout were more sensitive to cadmium than white sturgeon across all life stages, with median effect concentrations (hardness-normalized EC50s) ranging from 1.47 µg Cd/L to 2.62 µg Cd/L with sensitivity remaining consistent during later stages of development. Rainbow trout at 46 d posthatch (dph) ranked at the 2nd percentile of a compiled database for Cd species sensitivity distribution with an EC50 of 1.46 µg Cd/L and 72 dph sturgeon ranked at the 19th percentile (EC50 of 3.02 µg Cd/L). White sturgeon were more sensitive to copper than rainbow trout in 5 of the 7 life stages tested with biotic ligand model (BLM)-normalized EC50s ranging from 1.51 µg Cu/L to 21.9 µg Cu/L. In turn, rainbow trout at 74 dph and 95 dph were more sensitive to copper than white sturgeon at 72 dph and 89 dph, indicating sturgeon become more tolerant in older life stages, whereas older trout become more sensitive to copper exposure. White sturgeon at 2 dph, 16 dph, and 30 dph ranked in the lower percentiles of a compiled database for copper species sensitivity distribution, ranking at the 3rd (2 dph), 5th (16 dph), and 10th (30 dph) percentiles. White sturgeon were more sensitive to zinc than rainbow trout for 1 out of 7 life stages tested (2 dph with an biotic ligand model-normalized EC50 of 209 µg Zn/L) and ranked in the 1st percentile of a compiled database for zinc species sensitivity distribution.

  7. Acute sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to copper, cadmium, or zinc in water-only laboratory exposures

    USGS Publications Warehouse

    Calfee, Robin D.; Little, Edward E.; Puglis, Holly J.; Scott, Erinn L.; Brumbaugh, William G.; Mebane, Christopher A.

    2014-01-01

    The acute toxicity of cadmium, copper, and zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) were determined for 7 developmental life stages in flow-through water-only exposures. Metal toxicity varied by species and by life stage. Rainbow trout were more sensitive to cadmium than white sturgeon across all life stages, with median effect concentrations (hardness-normalized EC50s) ranging from 1.47 µg Cd/L to 2.62 µg Cd/L with sensitivity remaining consistent during later stages of development. Rainbow trout at 46 d posthatch (dph) ranked at the 2nd percentile of a compiled database for Cd species sensitivity distribution with an EC50 of 1.46 µg Cd/L and 72 dph sturgeon ranked at the 19th percentile (EC50 of 3.02 µg Cd/L). White sturgeon were more sensitive to copper than rainbow trout in 5 of the 7 life stages tested with biotic ligand model (BLM)-normalized EC50s ranging from 1.51 µg Cu/L to 21.9 µg Cu/L. In turn, rainbow trout at 74 dph and 95 dph were more sensitive to copper than white sturgeon at 72 dph and 89 dph, indicating sturgeon become more tolerant in older life stages, whereas older trout become more sensitive to copper exposure. White sturgeon at 2 dph, 16 dph, and 30 dph ranked in the lower percentiles of a compiled database for copper species sensitivity distribution, ranking at the 3rd (2 dph), 5th (16 dph), and 10th (30 dph) percentiles. White sturgeon were more sensitive to zinc than rainbow trout for 1 out of 7 life stages tested (2 dph with an biotic ligand model–normalized EC50 of 209 µg Zn/L) and ranked in the 1st percentile of a compiled database for zinc species sensitivity distribution.

  8. Acute sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to copper, cadmium, or zinc in water-only laboratory exposures

    PubMed Central

    Calfee, Robin D; Little, Edward E; Puglis, Holly J; Scott, Erinn; Brumbaugh, William G; Mebane, Christopher A

    2014-01-01

    The acute toxicity of cadmium, copper, and zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) were determined for 7 developmental life stages in flow-through water-only exposures. Metal toxicity varied by species and by life stage. Rainbow trout were more sensitive to cadmium than white sturgeon across all life stages, with median effect concentrations (hardness-normalized EC50s) ranging from 1.47 µg Cd/L to 2.62 µg Cd/L with sensitivity remaining consistent during later stages of development. Rainbow trout at 46 d posthatch (dph) ranked at the 2nd percentile of a compiled database for Cd species sensitivity distribution with an EC50 of 1.46 µg Cd/L and 72 dph sturgeon ranked at the 19th percentile (EC50 of 3.02 µg Cd/L). White sturgeon were more sensitive to copper than rainbow trout in 5 of the 7 life stages tested with biotic ligand model (BLM)-normalized EC50s ranging from 1.51 µg Cu/L to 21.9 µg Cu/L. In turn, rainbow trout at 74 dph and 95 dph were more sensitive to copper than white sturgeon at 72 dph and 89 dph, indicating sturgeon become more tolerant in older life stages, whereas older trout become more sensitive to copper exposure. White sturgeon at 2 dph, 16 dph, and 30 dph ranked in the lower percentiles of a compiled database for copper species sensitivity distribution, ranking at the 3rd (2 dph), 5th (16 dph), and 10th (30 dph) percentiles. White sturgeon were more sensitive to zinc than rainbow trout for 1 out of 7 life stages tested (2 dph with an biotic ligand model–normalized EC50 of 209 µg Zn/L) and ranked in the 1st percentile of a compiled database for zinc species sensitivity distribution. Environ Toxicol Chem 2014;33:2259–2272. © 2014. The Authors. This article is a US government work and, as such, is in the public domain in the United States of America. Environmental Toxicology and Chemistry published byWiley Periodicals, Inc. on behalf of SETAC. This is an open access article

  9. Managing Pain in Inflammatory Bowel Disease

    PubMed Central

    Jones, R. Carter W.; Wallace, Mark S.

    2011-01-01

    Pain is a common complaint in inflammatory bowel disease, and it has significant consequences for patients' quality of life. A thorough evaluation to determine the source of patients' pain should include clinical, laboratory, radiologic, and endoscopic assessments as indicated. Differentiating among active inflammation, secondary complications, and functional pain can be complicated. Even when all active disease is adequately treated, clinicians are often left with the difficulty of managing chronic pain. This paper will review the benefits and limitations of several commonly used treatments and promising future therapies. A suggested treatment algorithm will provide some guidance in this challenging area of inflammatory bowel disease management. PMID:22298998

  10. Computed tomographic studies of the painful abdomen

    SciTech Connect

    Benson, M.; Bree, R.L.; Schwab, R.E.; Ouimette, M.

    1985-05-01

    Abdominal CT scans were reviewed in a series of 53 patients who had abdominal pain without objective physical, radiographic, or laboratory abnormalities. Forty patients presented with abdominal pain alone, while the remaining patients had abdominal pain associated with nausea, vomiting or mild weight loss. Abdominal CT scans in all patients were interpreted as normal. One patient had a pancreatic carcinoma discovered at surgery one month after the CT scan was obtained. The patients were followed up for 6 to 12 months to confirm absence of significant disease. Our analysis suggests a very low yield from abdominal CT in patients with abdominal pain and no other objective findings.

  11. Glia and pain: is chronic pain a gliopathy?

    PubMed

    Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken

    2013-12-01

    Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions.

  12. The ruthenium NO donor, [Ru(bpy)2(NO)SO3](PF6), inhibits inflammatory pain: involvement of TRPV1 and cGMP/PKG/ATP-sensitive potassium channel signaling pathway.

    PubMed

    Staurengo-Ferrari, Larissa; Mizokami, Sandra S; Silva, Jean J; da Silva, Francisco O N; Sousa, Eduardo H S; da França, Luiz G; Matuoka, Mariana L; Georgetti, Sandra R; Baracat, Marcela M; Casagrande, Rubia; Pavanelli, Wander R; Verri, Waldiceu A

    2013-04-01

    The activation of nitric oxide (NO) production is an analgesic mechanism shared by drugs such as morphine and diclofenac. Therefore, the controlled release of low amounts of NO seems to be a promising analgesic approach. In the present study, the antinociceptive effect of the ruthenium NO donor [Ru(bpy)2(NO)SO3](PF6) (complex I) was investigated. It was observed that complex I inhibited in a dose (0.3-10mg/kg)-dependent manner the acetic acid-induced writhing response. At the dose of 1mg/kg, complex I inhibited the phenyl-p-benzoquinone-induced writhing response and formalin- and complete Freund's adjuvant-induced licking and flinch responses. Additionally, complex I also inhibited transient receptor potential cation channel subfamily V member 1 (TRPV1)-dependent overt pain-like behavior induced by capsaicin. Complex I also inhibited the carrageenin-induced mechanical hyperalgesia and increase of myeloperoxidase activity (MPO) in paw skin samples. The inhibitory effect of complex I in the carrageenin-induced hyperalgesia, MPO activity and formalin was prevented by the treatment with ODQ, KT5823 and glybenclamide, indicating that complex I inhibits inflammatory hyperalgesia by activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway. The present study demonstrates the efficacy of a novel ruthenium NO donor and its analgesic mechanisms.

  13. The biochemical origin of pain: the origin of all pain is inflammation and the inflammatory response. Part 2 of 3 - inflammatory profile of pain syndromes.

    PubMed

    Omoigui, Sota

    2007-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby briefly describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome/reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and serve as a foundation to be built upon by other researchers and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain

  14. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    PubMed

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  15. Visceral Pain and Gastrointestinal Microbiome

    PubMed Central

    Chichlowski, Maciej; Rudolph, Colin

    2015-01-01

    A complex set of interactions between the microbiome, gut and brain modulate responses to visceral pain. These interactions occur at the level of the gastrointestinal mucosa, and via local neural, endocrine or immune activity; as well as by the production of factors transported through the circulatory system, like bacterial metabolites or hormones. Various psychological, infectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain responses. There are critical sensitive periods that can impact visceral pain responses in adulthood. In this review we provide a brief background of the intestinal microbiome and emerging concepts of the bidirectional interactions between the microbiome, gut and brain. We also discuss recent work in animal models, and human clinical trials using prebiotics and probiotics that alter the microbiome with resultant alterations in visceral pain responses. PMID:25829337

  16. Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene

    SciTech Connect

    Chesler, Elissa J; Mogil, Jeffrey; Miermeister, Frank; Frank, Seifert; Strasburg, Kate; Zimmermann, Katharina; Reinold, Heiko; Austin, Jean; Bernardini, Nadia

    2005-01-01

    Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli. We further present convergent behavioral and electrophysiological evidence that the variable responses to noxious heat are due to strain-dependence of CGRP expression and sensitivity. Strain differences in behavioral response to noxious heat could be abolished by peripheral injection of CGRP, blockade of cutaneous and spinal CGRP receptors, or long-term inactivation of CGRP with a CGRP-binding Spiegelmer. Linkage mapping supports the contention that the genetic variant determining variable heat pain sensitivity across mouse strains affects the expression of the Calca gene that codes for CGRP

  17. Mechanisms of pain from urinary tract infection.

    PubMed

    Rosen, John M; Klumpp, David J

    2014-04-01

    The pain response to urinary tract infection is largely uncharacterized, but the symptomatic response to urinary tract infection contrasts with the lack of pain response among individuals with asymptomatic bacteriuria. Quantifying pelvic pain in a murine urinary tract infection model, uropathogenic Escerichia coli induces transient pelvic pain, whereas an asymptomatic bacteriuria E. coli isolate causes no pain, thus recapitulating the spectrum of clinical responses to intravesical E. coli. These differential pain responses are not correlated with bladder colonization or inflammation, but instead are intrinsic to E. coli lipopolysaccharide and dependent on the lipopolysaccharide receptor, TLR4. Epidemiological data suggest a link between interstitial cystitis and a history of urinary tract infection, so it was evaluated whether repetitive uropathogenic E. coli instillation would result in chronic pain through central sensitization. Although repeated infection with wild type uropathogenic E. coli results in only transient episodes of acute pain, a uropathogenic E. coli mutant lacking O-antigen causes chronic, post-urinary tract infection pelvic pain. Similarly, a K-12 E. coli strain lacking O-antigen induces chronic pain that persisted long after bacterial clearance, and expressing O-antigen nullified the pain phenotype. Spinal cords isolated from mice with post-urinary tract infection chronic pain showed deficits in short-term depression consistent with central sensitization. Deleting O-antigen gene complex from a uropathogenic E. coli strain and subsequent heterologous expression of O-antigen gene clusters shows that a single bacterial isolate can exhibit pain phenotypes ranging from a null phenotype, an acute pain phenotype, to a chronic pain phenotype. Post-urinary tract infection chronic pain is also associated with voiding dysfunction and anxious/depressive behavior. These effects are also mediated by TRPV1 at the level of pain establishment

  18. Neck pain

    PubMed Central

    2008-01-01

    Introduction Non-specific neck pain has a postural or mechanical basis and affects about two thirds of people at some stage, especially in middle age. Acute neck pain resolves within days or weeks, but may become chronic in about 10% of people. Whiplash injuries follow sudden acceleration–deceleration of the neck, such as in road traffic or sporting accidents. Up to 40% of people continue to report symptoms 15 years after the accident, although this varies between countries. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for people with non-specific neck pain without severe neurological deficit? What are the effects of treatments for acute whiplash injury? What are the effects of treatments for chronic whiplash injury? What are the effects of treatments for neck pain with radiculopathy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 91 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of the evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, biofeedback, drug treatments (analgesics, antidepressants, epidural steroid injections, muscle relaxants, non-steroidal anti-inflammatory drugs [NSAIDs]), early mobilisation, early return to normal activity, exercise, heat or cold, manipulation (alone or plus exercise), mobilisation, multimodal treatment, patient education, percutaneous radiofrequency neurotomy

  19. Spontaneous Chronic Pain After Experimental Thoracotomy Revealed by Conditioned Place Preference: Morphine Differentiates Tactile Evoked Pain From Spontaneous Pain.

    PubMed

    Hung, Ching-Hsia; Wang, Jeffrey Chi-Fei; Strichartz, Gary R

    2015-09-01

    Chronic pain after surgery limits social activity, interferes with work, and causes emotional suffering. A major component of such pain is reported as resting or spontaneous pain with no apparent external stimulus. Although experimental animal models can simulate the stimulus-evoked chronic pain that occurs after surgery, there have been no studies of spontaneous chronic pain in such models. Here the conditioned place preference (CPP) paradigm was used to reveal resting pain after experimental thoracotomy. Male Sprague Dawley rats received a thoracotomy with 1-hour rib retraction, resulting in evoked tactile hypersensitivity, previously shown to last for at least 9 weeks. Intraperitoneal injections of morphine (2.5 mg/kg) or gabapentin (40 mg/kg) gave equivalent 2- to 3-hour-long relief of tactile hypersensitivity when tested 12 to 14 days postoperatively. In separate experiments, single trial CPP was conducted 1 week before thoracotomy and then 12 days (gabapentin) or 14 days (morphine) after surgery, followed the next day by 1 conditioning session with morphine or gabapentin, both versus saline. The gabapentin-conditioned but not the morphine-conditioned rats showed a significant preference for the analgesia-paired chamber, despite the equivalent effect of the 2 agents in relieving tactile allodynia. These results show that experimental thoracotomy in rats causes spontaneous pain and that some analgesics, such as morphine, that reduce evoked pain do not also relieve resting pain, suggesting that pathophysiological mechanisms differ between these 2 aspects of long-term postoperative pain. Perspective: Spontaneous pain, a hallmark of chronic postoperative pain, is demonstrated here in a rat model of experimental postthoracotomy pain, further validating the use of this model for the development of analgesics to treat such symptoms. Although stimulus-evoked pain was sensitive to systemic morphine, spontaneous pain was not, suggesting different mechanistic

  20. The Role of Glutamate Dehydrogenase (GDH) Testing Assay in the Diagnosis of Clostridium difficile Infections: A High Sensitive Screening Test and an Essential Step in the Proposed Laboratory Diagnosis Workflow for Developing Countries like China.

    PubMed

    Cheng, Jing-Wei; Xiao, Meng; Kudinha, Timothy; Xu, Zhi-Peng; Sun, Lin-Ying; Hou, Xin; Zhang, Li; Fan, Xin; Kong, Fanrong; Xu, Ying-Chun

    2015-01-01

    The incidence and severity of Clostridium difficile infection (CDI) in North America and Europe has increased significantly since the 2000s. However, CDI is not widely recognized in China and other developing countries due to limited laboratory diagnostic capacity and low awareness. Most published studies on laboratory workflows for CDI diagnosis are from developed countries, and thus may not be suitable for most developing countries. Therefore, an alternative strategy for developing countries is needed. In this study, we evaluated the performance of the Glutamate Dehydrogenase (GDH) test and its associated workflow on 416 fecal specimens from suspected CDI cases. The assay exhibited excellent sensitivity (100.0%) and specificity (92.8%), compared to culture based method, and thus could be a good screening marker for C. difficile but not for indication of toxin production. The VIDAS CDAB assay, which can detect toxin A/B directly from fecal specimens, showed good specificity (99.7%) and positive predictive value (97.2%), but low sensitivity (45.0%) and negative predictive value (88.3%), compared with PCR-based toxin gene detection. Therefore, we propose a practical and efficient GDH test based workflow strategy for the laboratory diagnosis of CDI in developing countries like China. By applying this new workflow, the CDI laboratory diagnosis rate was notably improved in our center, yet the increasing cost was kept at a minimum level. Furthermore, to gain some insights into the genetic population structure of C. difficile isolates from our hospital, we performed MLST and PCR toxin gene typing.

  1. Pain Management: Post-Amputation Pain

    MedlinePlus

    Pain Management Post-Amputation Pain Volume 8 · Issue 2 · March/April 1998 Text size Larger text Smaller text Java Required Print page Save and share ... by G. Edward Jeffries, MD, FACS Post-Amputation Pain Post-amputation pain is one of the most ...

  2. Satisfaction with and Perception of Pain Management among Palliative Patients with Breakthrough Pain: A Qualitative Study.

    PubMed

    Pathmawathi, Subramanian; Beng, Tan Seng; Li, Lee Mei; Rosli, Roshaslina; Sharwend, Supermanian; Kavitha, Rasaiah R; Christopher, Boey Chiong Meng

    2015-08-01

    Breakthrough pain is a significant contributor to much suffering by patients. The experience of intense pain may interfere with, and affect, daily life functioning and has major consequences on patients' well-being if it is not well managed. The area of breakthrough pain has not been fully understood. This study thus aimed to explore the experiences of breakthrough pain among palliative patients. A qualitative study based on a series of open-ended interviews among 21 palliative patients suffering from pain at an urban tertiary hospital in Malaysia was conducted. Five themes were generated: (i) pain viewed as an unbearable experience causing misery in the lives of patients, (ii) deterioration of body function and no hope of recovery, (iii) receiving of inadequate pain management for pain, (iv) insensitivity of healthcare providers toward patients' pain experience, and (v) pain coping experiences of patients. The findings revealed that nonpharmacologic approaches such as psychosocial support should be introduced to the patients. Proper guidance and information should be given to healthcare providers to improve the quality of patient care. Healthcare providers should adopt a sensitive approach in caring for patients' needs. The aim is to meet the needs of the patients who want to be pain free or to attain adequate relief of their pain for breakthrough pain.

  3. B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina

    PubMed Central

    2011-01-01

    Background Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. Methods We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. Results 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively. The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. Conclusion BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS. Trial Registration ClinicalTrials.gov Identifier: NCT01377402. PMID:21958326

  4. Can Repeated Painful Blunt Impact Deter Approach Toward a Goal?

    DTIC Science & Technology

    2010-11-29

    1 CAN REPEATED PAINFUL BLUNT IMPACT DETER APPROACH TOWARD A GOAL? K. R. Short*, G. Reid, G. Cooke Target Behavioral Response Laboratory, US...Angeles, CA 90095 ABSTRACT Painful blunt impact from a low-mass, high-speed projectile has been considered as a possible non-lethal weapon for...accuracy. Blunt impacts produced varied pain ratings, but pain was not a predictive factor in any escape, avoidance, or performance measure. Subjects

  5. Pain in the foot. 2. Causes of pain in the hindfoot, midfoot, and forefoot.

    PubMed

    Mann, R A

    1987-07-01

    Pain in the foot has many causes. A careful history and physical examination, radiographs, and laboratory data usually yield the correct diagnosis so that specific treatment can be directed toward the problem to help relieve the patient's pain. Rarely is surgery necessary. Good conservative management usually produces a satisfactory clinical response.

  6. Back pain in astronauts (8-IML-1)

    NASA Technical Reports Server (NTRS)

    Wing, P. C.

    1992-01-01

    As a preliminary study for the International Microgravity Laboratory (IML-1) experiment, a pain diagram was used to elicit information about the incidence and severity of back pain experienced by 20 payload specialists (PS) on 22 shuttle flights from 1983 to 1986. There were 18 responses from 17 PSs (one PS provided information about two missions). Thirteen PSs (72 percent) reported experiencing some degree of back pain, ranging from dull (can be ignored) to severe, making concentration difficult. For the majority, the pain was dull in nature, and did not interfere with work or concentration. For some, the pain abated after only a few minutes; for others, the pain persisted for the entire duration of the flight.

  7. Assessment of Muscle Pain Induced by Elbow-Flexor Eccentric Exercise

    PubMed Central

    Lau, Wing Yin; Blazevich, Anthony J.; Newton, Michael J.; Wu, Sam Shi Xuan; Nosaka, Kazunori

    2015-01-01

    Context: Delayed-onset muscle soreness (DOMS) is a common muscle pain that many people experience and is often used as a model of acute muscle pain. Researchers have reported the effects of various interventions on DOMS, but different DOMS assessment protocols used in these studies make it difficult to compare the effects. Objective: To investigate DOMS characteristics after elbow-flexor eccentric exercise to establish a standardized DOMS assessment protocol. Design: Descriptive laboratory study. Setting: Research laboratory. Patients or Other Participants: Ten healthy, untrained men (21–39 years). Intervention(s): Participants performed 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors. Main Outcome Measure(s): Indirect muscle-damage markers were maximal voluntary isometric contraction torque, range of motion, and serum creatine kinase activity. Muscle pain was assessed before exercise, immediately postexercise, and 1 to 5 days postexercise using (1) a visual analog scale (VAS), (2) a category ratio-10 scale (CR-10) when applying static pressure and palpation at different sites (3, 9, and 15 cm above the elbow crease), and (3) pressure-pain thresholds (PPTs) at 50 sites (pain mapping). Results: Maximal voluntary isometric contraction and range of motion decreased and creatine kinase activity increased postexercise, indicating muscle damage. Palpation induced greater pain than static pressure, and longitudinal and transverse palpations induced greater pain than circular palpation (P < .05). The PPT was lower in the medial region before exercise, but the pain-sensitive regions shifted to the central and distal regions of the biceps brachii at 1 to 3 days postexercise (P < .05). The VAS was correlated with the CR-10 scale (r = 0.91, P < .05) but not with the PPT (r = −0.28, P = .45). Conclusions: The way in which muscles are assessed affects the pain level score. This finding suggests that pain level and pain threshold cannot be used

  8. Analgesic Microneedle Patch for Neuropathic Pain Therapy.

    PubMed

    Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Wang, Ji; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Yeomans, David C; Wu, Mei X; Xie, Xinmin Simon

    2017-01-24

    Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

  9. [Fetal pain - neurobiological causes and consequences].

    PubMed

    Gonçalves, Nuno; Rebelo, Sandra; Tavares, Isaura

    2010-01-01

    The existence of putatively painful situations to the fetus demands a careful evaluation of the issue of fetal pain. Several indirect approaches are used to evaluate the existence of fetal pain. Neurobiological studies showed that from the 30th week on, the anatomical and physiological system for pain transmission is already developed, with the connections from the periphery to the cortex being successively established. Stress responses to a painful stimulation are complex but they can be detected from the 16th week on. There is activation of the hypothalamus-pituitary-adrenal axis, autonomic nervous system and hemodynamic changes in response to nociceptive stimulation. In prematures exposed to pain there are significant increases of adrenaline, noradrenaline and cortisol, hemodynamic changes, motor reflexes and facial reactions. The changes induced by strong nociceptive stimulation of newborns have important postnatal consequences since they affect future reactions to noxious stimuli. Central sensitization and immaturity of the pain inhibitory system are the main neurobiological explanations for the increased pain. Detailed studies of the neurobiological mechanisms of the transmission of painful stimuli along with follow-up studies of the consequences of exposure to pain during the development of the fetus are necessary to fully understand fetal pain.

  10. Undertreatment of caner pain.

    PubMed

    Wang, Cheng-Hsu; Lee, Shiu-Yu C

    2015-06-01

    Pain is a burdensome symptom that can commonly exist chronically along the cancer trajectory. Uncontrolled pain will impact on cancer patients' quality of life, even further negatively affect cancer survivors' employment. Based on systemic reviews of studies for past 10 years, the paper reported that although there is enormous advancement on the knowledge of cancer pain and pain management, studies still documented undertreatment of cancer pain globally. Additionally, pain distress a significant portion of cancer survivors. The pain in cancer survivors distinct from the pain related with cancer, instead emphasize on pain related with cancer treatment, such as neuropathic pain, muscular syndrome. Evidence-based pain management with common pain problems in cancer survivors is lacking. Further studies are needed to understand the pain in cancer survivors and to develop effective strategies in helping cancer survivors to manage their pain.

  11. Effects of coping statements on experimental pain in chronic pain patients.

    PubMed

    Roditi, Daniela; Robinson, Michael E; Litwins, Nola

    2009-08-19

    The present study measured the effects of catastrophizing self-statements and positive coping self-statements on cold pressor-induced pain. Participants were 58 adult chronic pain patients with current facial pain. It was hypothesized that catastrophizing would lead to a decrease in pain endurance whereas positive coping would lead to an increase in pain endurance. It was also hypothesized that catastrophizing would lead to an increase in peak pain intensity whereas positive coping would lead to a decrease in peak pain intensity. At pretest, participants submerged their nondominant hand in the cold pressor. Pain sensitivity ranges (PSR) were subsequently determined by calculating the difference between tolerance and threshold times. Ratings of peak pain intensity were measured using a pressure sensitive bladder/transducer. Participants underwent random assignment to either a catastrophizing group or a positive coping self-statement group. ANCOVA results revealed that on average, participants employing catastrophizing statements as a coping strategy experienced significantly lower PSR (M = 35.53, SD = 39.71) compared to participants employing positive coping self-statements (M = 73.70, SD = 86.14) when controlling for pretest PSR. Group assignment had no significant influence on peak pain intensity ratings. Thus, our results reveal that manipulation of coping causes changes in pain endurance.

  12. Conditioned Pain Modulation and Situational Pain Catastrophizing as Preoperative Predictors of Pain following Chest Wall Surgery: A Prospective Observational Cohort Study

    PubMed Central

    Grosen, Kasper; Vase, Lene; Pilegaard, Hans K.; Pfeiffer-Jensen, Mogens; Drewes, Asbjørn M.

    2014-01-01

    Background Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency. Methods Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively. Results Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001). Conclusions Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative

  13. A population-based study of quantitative sensory testing in adolescents with and without chronic pain.

    PubMed

    Tham, See Wan; Palermo, Tonya M; Holley, Amy Lewandowski; Zhou, Chuan; Stubhaug, Audun; Furberg, Anne-Sofie; Nielsen, Christopher Sivert

    2016-12-01

    Quantitative sensory testing (QST) has been used to characterize pain sensitivity in individuals with and without pain conditions. Research remains limited in pediatric populations, hindering the ability to expand the utility of QST toward its potential application in clinical settings and clinical predictive value. The aims of this study were to examine pain sensitivity using QST in adolescents with chronic pain compared to adolescents without chronic pain and identify predictors of pain sensitivity. A population-based study conducted from 2010 to 2011 provided data on 941 adolescents, 197 were classified as having chronic pain and 744 were classified without chronic pain. Self-reported data on pain characteristics, psychological functioning, and QST responses were examined. The findings revealed lower pressure pain threshold and tolerance on the trapezius (P's = 0.03) in adolescents with chronic pain compared to adolescents without chronic pain, but no differences on heat or cold-pressor pain tasks. Female sex (P's = 0.02) and poorer psychological functioning (P's = 0.02) emerged as significant predictors of greater pain sensitivity across all pain modalities. Exploratory analyses revealed several associations between clinical pain characteristics and QST responses within the chronic pain cohort. Findings from this large pediatric sample provide comprehensive data that could serve as normative data on QST responses in adolescents with and without chronic pain. These findings lay the groundwork toward developing future QST research and study protocols in pediatric populations, taking into consideration sex and psychological distress.

  14. Definitions and Types of Pain

    MedlinePlus

    ... Therapy Pain Management Recommendations References April 15, 2017 Definitions and Types of Pain Defining Pain Pain is ... there are many mechanisms involved in nociception. More definitions ... Classifying Pain Pain can be "acute" or "chronic." ...

  15. Conditioned pain modulation in women with irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 corti...

  16. CXTFIT/Excel A modular adaptable code for parameter estimation, sensitivity analysis and uncertainty analysis for laboratory or field tracer experiments

    SciTech Connect

    Tang, Guoping; Mayes, Melanie; Parker, Jack C; Jardine, Philip M

    2010-01-01

    We implemented the widely used CXTFIT code in Excel to provide flexibility and added sensitivity and uncertainty analysis functions to improve transport parameter estimation and to facilitate model discrimination for multi-tracer experiments on structured soils. Analytical solutions for one-dimensional equilibrium and nonequilibrium convection dispersion equations were coded as VBA functions so that they could be used as ordinary math functions in Excel for forward predictions. Macros with user-friendly interfaces were developed for optimization, sensitivity analysis, uncertainty analysis, error propagation, response surface calculation, and Monte Carlo analysis. As a result, any parameter with transformations (e.g., dimensionless, log-transformed, species-dependent reactions, etc.) could be estimated with uncertainty and sensitivity quantification for multiple tracer data at multiple locations and times. Prior information and observation errors could be incorporated into the weighted nonlinear least squares method with a penalty function. Users are able to change selected parameter values and view the results via embedded graphics, resulting in a flexible tool applicable to modeling transport processes and to teaching students about parameter estimation. The code was verified by comparing to a number of benchmarks with CXTFIT 2.0. It was applied to improve parameter estimation for four typical tracer experiment data sets in the literature using multi-model evaluation and comparison. Additional examples were included to illustrate the flexibilities and advantages of CXTFIT/Excel. The VBA macros were designed for general purpose and could be used for any parameter estimation/model calibration when the forward solution is implemented in Excel. A step-by-step tutorial, example Excel files and the code are provided as supplemental material.

  17. CXTFIT/Excel-A modular adaptable code for parameter estimation, sensitivity analysis and uncertainty analysis for laboratory or field tracer experiments

    NASA Astrophysics Data System (ADS)

    Tang, Guoping; Mayes, Melanie A.; Parker, Jack C.; Jardine, Philip M.

    2010-09-01

    We implemented the widely used CXTFIT code in Excel to provide flexibility and added sensitivity and uncertainty analysis functions to improve transport parameter estimation and to facilitate model discrimination for multi-tracer experiments on structured soils. Analytical solutions for one-dimensional equilibrium and nonequilibrium convection dispersion equations were coded as VBA functions so that they could be used as ordinary math functions in Excel for forward predictions. Macros with user-friendly interfaces were developed for optimization, sensitivity analysis, uncertainty analysis, error propagation, response surface calculation, and Monte Carlo analysis. As a result, any parameter with transformations (e.g., dimensionless, log-transformed, species-dependent reactions, etc.) could be estimated with uncertainty and sensitivity quantification for multiple tracer data at multiple locations and times. Prior information and observation errors could be incorporated into the weighted nonlinear least squares method with a penalty function. Users are able to change selected parameter values and view the results via embedded graphics, resulting in a flexible tool applicable to modeling transport processes and to teaching students about parameter estimation. The code was verified by comparing to a number of benchmarks with CXTFIT 2.0. It was applied to improve parameter estimation for four typical tracer experiment data sets in the literature using multi-model evaluation and comparison. Additional examples were included to illustrate the flexibilities and advantages of CXTFIT/Excel. The VBA macros were designed for general purpose and could be used for any parameter estimation/model calibration when the forward solution is implemented in Excel. A step-by-step tutorial, example Excel files and the code are provided as supplemental material.

  18. 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

  19. Biological and neurodevelopmental implications of neonatal pain.

    PubMed

    Walker, Suellen M

    2013-09-01

    Nociceptive pathways are functional following birth. In addition to physiological and behavioral responses, neurophysiological measures and neuroimaging evaluate nociceptive pathway function and quantify responses to noxious stimuli in preterm and term neonates. Intensive care and surgery can expose neonates to painful stimuli when the developing nervous system is sensitive to changing input, resulting in persistent impacts into later childhood. Early pain experience has been correlated with increased sensitivity to subsequent painful stimuli, impaired neurodevelopmental outcomes, and structural changes in brain development. Parallel preclinical studies have elucidated underlying mechanisms and evaluate preventive strategies to inform future clinical trials.

  20. Central Neuropathic Pain Syndromes.

    PubMed

    Watson, James C; Sandroni, Paola

    2016-03-01

    Chronic pain is common in patients with neurologic complications of a central nervous system insult such as stroke. The pain is most commonly musculoskeletal or related to obligatory overuse of neurologically unaffected limbs. However, neuropathic pain can result directly from the central nervous system injury. Impaired sensory discrimination can make it challenging to differentiate central neuropathic pain from other pain types or spasticity. Central neuropathic pain may also begin months to years after the injury, further obscuring recognition of its association with a past neurologic injury. This review focuses on unique clinical features that help distinguish central neuropathic pain. The most common clinical central pain syndromes-central poststroke pain, multiple sclerosis-related pain, and spinal cord injury-related pain-are reviewed in detail. Recent progress in understanding of the pathogenesis of central neuropathic pain is reviewed, and pharmacological, surgical, and neuromodulatory treatments of this notoriously difficult to treat pain syndrome are discussed.

  1. A laboratory exercise for a college-level, introductory neuroscience course demonstrating effects of housing environment on anxiety and psychostimulant sensitivity.

    PubMed

    Pritchard, Laurel M; Van Kempen, Tracey A; Williams, Heather; Zimmerberg, Betty

    2008-01-01

    In this paper we describe a lab exercise developed for the Introduction to Neuroscience course at Williams College. One of a series of five labs, this exercise demonstrated several key principles of behavioral neuroscience. In this lab, students explored the effects of post-weaning housing environment on anxiety-like behavior and psychostimulant sensitivity in rodents. The exercise was intended to emphasize the importance and utility of animal models in neuroscience research and to give students hands-on experience with behavioral neuroscience research techniques. Students tested rats reared in social isolation or environmental enrichment for anxiety-like behaviors on the elevated plus maze, and for spontaneous and amphetamine-induced locomotor activity in the open field. They were then asked to analyze pooled class data and prepare a short lab report. Overall, student performance was excellent. This exercise emerged as a class favorite on course evaluations. Interestingly, the first time this exercise was conducted, the effects of environmental enrichment on anxiety-like behaviors and psychostimulant sensitivity were not consistent with those published in previous studies. Key methodological issues that may account for this discrepancy and contribute to successful implementation by other programs are discussed.

  2. Measurement Properties of the Non-Communicating Adult Pain Checklist (NCAPC): A Pain Scale for Adults with Intellectual and Developmental Disabilities, Scored in a Clinical Setting

    ERIC Educational Resources Information Center

    Lotan, M.; Moe-Nilssen, R.; Ljunggren, A. E.; Strand, L. I.

    2010-01-01

    The 18 items' Non-Communicating Adult Pain Checklist (NCAPC) has been developed from the 27 items Non-Communicating Children Pain Checklist to better capture pain behavior of adults with Intellectual and Developmental Disabilities (IDD). As part of the NCAPC's measurement properties, internal consistency, reliability and sensitivity to pain have…

  3. Pain insensitivity syndrome misinterpreted as inflicted burns.

    PubMed

    van den Bosch, Gerbrich E; Baartmans, Martin G A; Vos, Paul; Dokter, Jan; White, Tonya; Tibboel, Dick

    2014-05-01

    We present a case study of a 10-year-old child with severe burns that were misinterpreted as inflicted burns. Because of multiple injuries since early life, the family was under suspicion of child abuse and therefore under supervision of the Child Care Board for 2 years before the boy was burned. Because the boy incurred the burns without feeling pain, we conducted a thorough medical examination and laboratory testing, evaluated detection and pain thresholds, and used MRI to study brain morphology and brain activation patterns during pain between this patient and 3 healthy age- and gender-matched controls. We found elevated detection and pain thresholds and lower brain activation during pain in the patient compared with the healthy controls and reference values. The patient received the diagnosis of hereditary sensory and autonomic neuropathy type IV on the basis of clinical findings and the laboratory testing, complemented with the altered pain and detection thresholds and MRI findings. Hereditary sensory and autonomic neuropathy IV is a very rare congenital pain insensitivity syndrome characterized by the absence of pain and temperature sensation combined with oral mutilation due to unawareness, fractures, and anhidrosis caused by abnormalities in the peripheral nerves. Health care workers should be aware of the potential presence of this disease to prevent false accusations of child abuse.

  4. Neuropathic Pain After Lung Surgery

    ClinicalTrials.gov

    2016-11-08

    Chronic Neuropathic Pain, Postoperative; Chronic Pain, Postoperative; Chronic Chemotherapy-induced Neuropathic Pain; Chronic Chemotherapy-induced Pain; Chronic Chemotherapy-induced Peripheral Neuropathy

  5. Pain and pain management in haemophilia

    PubMed Central

    Auerswald, Günter; Dolan, Gerry; Duffy, Anne; Hermans, Cedric; Jiménez-Yuste, Victor; Ljung, Rolf; Morfini, Massimo; Lambert, Thierry; Šalek, Silva Zupančić

    2016-01-01

    Joint pain is common in haemophilia and may be acute or chronic. Effective pain management in haemophilia is essential to reduce the burden that pain imposes on patients. However, the choice of appropriate pain-relieving measures is challenging, as there is a complex interplay of factors affecting pain perception. This can manifest as differences in patients’ experiences and response to pain, which require an individualized approach to pain management. Prophylaxis with factor replacement reduces the likelihood of bleeds and bleed-related pain, whereas on-demand therapy ensures rapid bleed resolution and pain relief. Although use of replacement or bypassing therapy is often the first intervention for pain, additional pain relief strategies may be required. There is an array of analgesic options, but consideration should be paid to the adverse effects of each class. Nevertheless, a combination of medications that act at different points in the pain pathway may be beneficial. Nonpharmacological measures may also help patients and include active coping strategies; rest, ice, compression, and elevation; complementary therapies; and physiotherapy. Joint aspiration may also reduce acute joint pain, and joint steroid injections may alleviate chronic pain. In the longer term, increasing use of prophylaxis or performing surgery may be necessary to reduce the burden of pain caused by the degenerative effects of repeated bleeds. Whichever treatment option is chosen, it is important to monitor pain and adjust patient management accordingly. Beyond specific pain management approaches, ongoing collaboration between multidisciplinary teams, which should include physiotherapists and pain specialists, may improve outcomes for patients. PMID:27439216

  6. Discovering new treatments for sensitive teeth: the long path from biology to therapy.

    PubMed

    Markowitz, K; Pashley, D H

    2008-04-01

    Tooth sensitivity is a common dental pain condition where sufferers experience brief episodes of sharp well-localized pain when their teeth are subjected innocuous stimuli such as cold, air-currents and probing with a metallic instrument. In this review, we will make no attempt to describe all the treatments that have been developed to treat tooth sensitivity. We will review the basic anatomic and physiological mechanisms responsible for sensitivity. The insights into the dental lesions responsible for tooth sensitivity, as well as the physiological processes linking stimuli and pain generation have suggested several treatments and preventive strategies. Unfortunately, many tooth sensitivity treatments fail to perform better than placebos in clinical trials that seek to assess the effect of agents on pain symptoms. In the case of the most commonly used self-applied desensitizing agent, potassium salts, the mechanism of action established by laboratory and animal models may not apply to clinical use. Thus results obtained with laboratory and animal models must be applied with care to clinical use. Clinical literature suggests that tooth sensitivity is the symptomatic manifestation of significant dental problems, such as wear and other forms of non-carious tooth structure loss. These conditions are increasing in frequency as people age, retaining their natural teeth longer. They are frequently the consequences of aggressive oral hygiene practices and diets rich in acids. Treatments directed at the underlying causes rather than the symptoms of tooth sensitivity would hinder the development of these lesions and provide researchers with objective targets for assessing therapeutic efficacy.

  7. Histamine-induced itch converts into pain in neuropathic hyperalgesia.

    PubMed

    Baron, R; Schwarz, K; Kleinert, A; Schattschneider, J; Wasner, G

    2001-11-16

    Physiologically, itch and pain are transmitted in separate specific peripheral C-units and central afferent pathways. Some neuropathic pain patients with intact but sensitized (irritable) primary C-nociceptors have spontaneous pain, heat hyperalgesia, static and dynamic mechanical hyperalgesia. The question was whether cutaneous histamine application induces pain in these patients. For comparison histamine was applied into normal skin experimentally sensitized by capsaicin. Histamine application in the capsaicin-induced primary or secondary hyperalgesic skin did not change the intensity and quality of capsaicin pain. Itch was profoundly inhibited. Conversely, histamine application in neuropathic skin induced severe increase in spontaneous burning pain but no itch. In neuropathies irritable nociceptors may express histamine receptors or induce central sensitization to histaminergic stimuli so that itch converts into pain.

  8. [Pain and its main transmitters].

    PubMed

    Costentin, J

    2000-03-01

    The pain message originates peripherally from a great variety of substances either released from preformed stores or extemporaneously synthetized. They stimulate or sensitize nociceptors which are associated with the peripheral endings of sensitive protoneurones. Their central endings release many types of transmitters in the dorsal horn of medulla (substance P, NO, CGRP.). At this level their release, triggered by the firing rate, is modulated by the stimulation of various presynaptic receptors operated by transmitters produced by either interneurones (enkephalins) or medullar descending neurons (dopamine, norepinephrine, serotonine). These modulations correspond to the so-called gate control. The sensitive consecutive neurones which climb towards various brain areas are submitted to contradictory influences. Several of them enhance the pain perception (nociceptin, cholecystokinin, neuropeptide FF.) whereas several other reduce it (endorphines, neurotensin, neuromedin N, anandamide.).

  9. Acute and chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures

    USGS Publications Warehouse

    Ingersoll, Christopher G.; Contributions by Wang, Ning; Calfee, Robin D.; Beahan, Erinn; Brumbaugh, William G.; Dorman, Rebecca A.; Hardesty, Doug K.; Kunz, James L.; Little, Edward E.; Mebane, Christopher A.; Puglis, Holly J.

    2014-01-01

    White sturgeon (Acipenser transmontanus) are experiencing poor recruitment in the trans boundary reach of the upper Columbia River in eastern Washington State. Limited toxicity data indicated that early life stages of white sturgeon are sensitive to metals. In acute 4-day (d) exposures with larval white sturgeon, previous studies have reported that the 4-day median lethal concentrations (LC50) based on biotic ligand model (BLM) normalization for copper were below the U.S. Environmental Protection Agency national recommended acute water-quality criterion. In previously published chronic 66-d exposures starting with newly fertilized eggs of white sturgeon, 20-percent lethal effect concentrations (LC20s) for copper, cadmium, or zinc generally were within a factor of two of the chronic values of the most sensitive fish species in the databases of the U.S. Environmental Protection Agency water-quality criteria (WQC) for the three metals. However, there were some uncertainties in the chronic exposures previously performed with white sturgeon, including (1) low control survival (37 percent), (2) more control fish tested in each replicate compared to other treatments, (3) limited replication of treatments (n=2), (4) lack of reported growth data (such as dry weight), and (5) wide dilution factors for exposure concentrations (6- to 8-fold dilutions). The U.S. Environmental Protection Agency concluded that additional studies are needed to generate more toxicity data to better define lethal and sublethal toxicity thresholds for metals for white sturgeon. The objective of the study was to further evaluate the acute and chronic toxicity of cadmium, copper, lead, or zinc to early life stages of white sturgeon in water-only exposures. Toxicity tests also were performed with commonly tested rainbow trout (Oncorhynchus mykiss) under similar test conditions to determine the relative sensitivity between white sturgeon and rainbow trout to these metals. Toxicity data generated from

  10. Absorbing aerosols over Asia: A Geophysical Fluid Dynamics Laboratory general circulation model sensitivity study of model response to aerosol optical depth and aerosol absorption

    NASA Astrophysics Data System (ADS)

    Randles, C. A.; Ramaswamy, V.

    2008-11-01

    Forcing by absorbing atmospheric black carbon (BC) tends to heat the atmosphere, cool the surface, and reduce the surface latent and sensible heat fluxes. BC aerosol can have a large impact on regional climates and the hydrologic cycle. However, significant uncertainties remain concerning the increases in (1) the total amount of all aerosol species and (2) the amount of aerosol absorption that may have occurred over the 1950-1990 period. Focusing on south and east Asia, the sensitivity of a general circulation model's climate response (with prescribed sea surface temperatures and aerosol distributions) to such changes is investigated by considering a range of both aerosol absorption and aerosol extinction optical depth increases. We include direct and semidirect aerosol effects only. Precipitation changes are less sensitive to changes in aerosol absorption optical depth at lower aerosol loadings. At higher-extinction optical depths, low-level convergence and increases in vertical velocity overcome the stabilizing effects of absorbing aerosols and enhance the monsoonal circulation and precipitation in northwestern India. In contrast, the presence of increases in only scattering aerosols weakens the monsoonal circulation and inhibits precipitation here. Cloud amount changes can enhance or counteract surface solar flux reduction depending on the aerosol loading and absorption, with the changes also influencing the surface temperature and the surface energy balance. The results have implications for aerosol reduction strategies in the future that seek to mitigate air pollution concerns. At higher optical depths, if absorbing aerosol is present, reduction of scattering aerosol alone has a reduced effect on precipitation changes, implying that reductions in BC aerosols should be undertaken at the same time as reductions in sulfate aerosols.

  11. PERSISTENT BREAST PAIN FOLLOWING BREAST CANCER SURGERY IS ASSOCIATED WITH PERSISTENT SENSORY CHANGES, PAIN INTERFERENCE, AND FUNCTIONAL IMPAIRMENTS

    PubMed Central

    Langford, Dale J.; Paul, Steven M.; West, Claudia; Levine, Jon D.; Hamolsky, Deborah; Elboim, Charles; Schmidt, Brian L.; Cooper, Bruce A.; Abrams, Gary; Aouizerat, Bradley E.; Miaskowski, Christine

    2014-01-01

    Inter-individual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify three subgroups of women (n=398) with distinct persistent breast pain trajectories over six months following surgery (i.e., Mild, Moderate, Severe). Purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, determine how changes over time, in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60% to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the Severe Pain class reported higher scores than women in the Moderate Pain class. In addition, women in the Moderate Pain class reported higher scores than women in the Mild Pain class. Compared to the Mild Pain class, women in the Severe Pain class had significantly impaired grip strength and women in the Moderate and Severe Pain classes had impaired flexion and abduction. PMID:25439318

  12. Evolution: The Advantage of ‘Maladaptive’ Pain Plasticity

    PubMed Central

    Price, Theodore J.; Dussor, Gregory

    2015-01-01

    Following injury, nociceptive systems become sensitized, leading to heightened pain perception. The evolutionary reason for this phenomenon has been hard to pinpoint. A study in squid now suggests that nociceptive sensitization enhances survival from predators. PMID:24845663

  13. [The physiopathological mechanisms behind chronic myofacial pain].

    PubMed

    Ernberg, Malin

    2002-08-08

    Chronic orofacial myalgia is characterized by muscle pain, tenderness, stiffness, and restricted range of mandibular movement. It can be localized and due to temporomandibular disorders, or part of a generalized myalgia, e.g. fibromyalgia. The etiology and pathophysiology are unclear, but it is reasonable to assume that both peripheral and central mechanisms take part. Peripheral sensitization by serotonin and other mediators is a possible mechanism behind the development and modulation of chronic myalgia, while amplification of pain due to central sensitization in conjunction with disordered antinociception may represent the mechanisms for the maintenance of pain. Central sensitization seems to involve wind-up phenomena due to activation of N-methyl-D-aspartate receptors located on second-order neurons in the brainstem. Derangements in descending endogenous pain modulating systems due to central serotonin deficiency may explain the disordered antinociception.

  14. Gluten Sensitivity.

    PubMed

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on

  15. Medications for back pain

    MedlinePlus

    ... doses of these medicines can help with chronic low back pain , even if the person does not feel sad ... notices pain. Antidepressants most commonly used for chronic low back pain also help you sleep. Antidepressants most often used ...

  16. Back Pain During Pregnancy

    MedlinePlus

    ... Education & Events Advocacy For Patients About ACOG Back Pain During Pregnancy Home For Patients Search FAQs Back ... During Pregnancy FAQ115, January 2016 PDF Format Back Pain During Pregnancy Pregnancy What causes back pain during ...

  17. Pain medications - narcotics

    MedlinePlus

    Painkillers; Drugs for pain; Analgesics; Opioids ... Narcotics are also called opioid pain relievers. They are used only for pain that is severe and is not helped by other types of painkillers. When used ...

  18. Complex Regional Pain Syndrome

    MedlinePlus

    ... regional pain syndrome is an uncommon form of chronic pain that usually affects an arm or a leg. ... exercises may be. Transcutaneous electrical nerve stimulation (TENS) . Chronic pain is sometimes eased by applying electrical impulses to ...

  19. The Long Road of Pain: Chronic Pain Increases Perceived Distance

    PubMed Central

    Witt, Jessica K.; Linkenauger, Sally A.; Bakdash, Jonathan Z.; Augustyn, Jason S.; Cook, Andrew J.; Proffitt, Dennis R.

    2011-01-01

    Spatial perception is sensitive to the energetic costs required to perform intended actions. For example, hills look steeper to people who are fatigued or burdened by a heavy load. Similarly, perceived distance is also influenced by the energy required to walk or throw to a target. Such experiments demonstrate that perception is a function, not just of optical information, but also of the perceiver’s potential to act and the energetic costs associated with the intended action. In the current paper, we expand on the notion of “cost” by examining perceived distance in patients diagnosed with chronic pain, a multifactorial disease, which is experienced while walking. We found that chronic pain patients perceive target distances to be farther away than a control group. These results indicate the physical, and perhaps emotional, costs of chronic pain affect spatial perceptions. PMID:18949471

  20. Research into pain perception with arteriovenous fistula (avf) cannulation.

    PubMed

    Figueiredo, Ana E; Viegas, Ariani; Monteiro, Mara; Poli-de-Figueiredo, Carlos E

    2008-12-01

    Patients with end-stage renal failure (ESRF) undergoing haemodialysis (HD) are repeatedly exposed to stress and pain from approximately 300 punctures per year to their arteriovenous fistula (AVF). Repeated AVF punctures lead to a considerable degree of pain, due to the calibre and length of the bevel of fistula needles. Pain is a sensitive, emotional and subjective experience. The objective of this study was to measure pain associated with AVF needling. The analogue visual scale (AVS) divided into 10 equal parts (0 indicating lack of pain, and 10 unbearable pain) was used. Patients(7) perceptions were measured in three different HD sessions. Pain was considered mild during AVF needling. The buttonhole technique caused a mean degree of pain of 2.4 (+/-1.7), compared to 3.1 (+/-2.3) using the conventional ropeladder technique. Although without reaching a statistically significant difference, diminished pain was associated with the buttonhole technique.

  1. Updated Mechanisms of Sickle Cell Disease-Associated Chronic pain

    PubMed Central

    Lutz, Brianna; Meiler, Steffen E.; Bekker, Alex; Tao, Yuan-Xiang

    2015-01-01

    Sickle cell disease (SCD), a hemoglobinopathy, causes sickling of red blood cells, resulting in vessel blockage, stroke, anemia, inflammation, and extreme pain. A vast majority of SCD patients experience pain on a chronic basis, and many turn to opioids to provide limited relief. The side effects that come with chronic opioid use push for research into understanding the specific mechanisms of SCD-associated chronic pain. Current advances in SCD-associated pain have focused on alterations in the pain pathway including nociceptor sensitization and endogenous pain inducers. This article reviews the underlying pathophysiology of SCD, potential pain mechanisms, current treatments and their mechanism of action, and future directions of SCD-associated pain management. The information provided could help propel research in SCD-associated chronic pain and uncover novel treatment options for clinicians. PMID:26301256

  2. Asian Aerosols: A Geophysical Fluid Dynamics Laboratory general circulation model sensitivity study of model response to aerosol optical depth and aerosol absorption

    NASA Astrophysics Data System (ADS)

    Randles, C. A.; Ramaswamy, V.

    2007-12-01

    Atmospheric absorption by black carbon (BC) aerosol heats the atmosphere while simultaneously cooling the surface and reducing latent and sensible heat fluxes from the land. Recent studies have shown that absorbing BC aerosol can have a large impact on regional climates, including modification of the hydrological cycle. However, significant uncertainties remain with regards to (a) the total amount of all aerosol species and (b) the amount of aerosol absorption. Here we present a GCM sensitivity study focusing on the influences due to total aerosol amount and aerosol absorption in the south and east Asian regions. Six experiments are conducted to test the equilibrium response of the GFDL AM2 GCM (under conditions of prescribed, observed sea surface temperatures) to (i) changes in aerosol absorption caused by changes in BC aerosol amount, and (ii) aerosol extinction optical depth increases corresponding to the year 1990 relative to a control case of 1950. In order to systematically explore the uncertainties in aerosol loading and absorption, the sensitivity experiments are classified into four regimes: low extinction optical depth, low absorption; low extinction optical depth, high absorption; high extinction optical depth, low absorption; and high extinction optical depth, high absorption. Changes in surface temperature and changes in the hydrological cycle are generally insignificant when lower aerosol extinction optical depths are considered. For higher extinction optical depths, the change in the modeled regional circulation relative to the control circulation over south and east Asia is affected by the amount of aerosol absorption and contrasts sharply to the regional circulation change associated with increasing only scattering aerosols. When increasing absorbing aerosols over the region, low-level convergence and increases in vertical velocity overcome the stabilizing effects of the absorbing aerosol and enhance the monsoonal circulation and precipitation rate

  3. Acute psychosocial stress reduces pain modulation capabilities in healthy men.

    PubMed

    Geva, Nirit; Pruessner, Jens; Defrin, Ruth

    2014-11-01

    Anecdotes on the ability of individuals to continue to function under stressful conditions despite injuries causing excruciating pain suggest that acute stress may induce analgesia. However, studies exploring the effect of acute experimental stress on pain perception show inconsistent results, possibly due to methodological differences. Our aim was to systematically study the effect of acute stress on pain perception using static and dynamic, state-of-the-art pain measurements. Participants were 29 healthy men who underwent the measurement of heat-pain threshold, heat-pain intolerance, temporal summation of pain, and conditioned pain modulation (CPM). Testing was conducted before and during exposure to the Montreal Imaging Stress Task (MIST), inducing acute psychosocial stress. Stress levels were evaluated using perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol. The MIST induced a significant stress reaction. Although pain threshold and pain intolerance were unaffected by stress, an increase in temporal summation of pain and a decrease in CPM were observed. These changes were significantly more robust among individuals with stronger reaction to stress ("high responders"), with a significant correlation between the perception of stress and the performance in the pain measurements. We conclude that acute psychosocial stress seems not to affect the sensitivity to pain, however, it significantly reduces the ability to modulate pain in a dose-response manner. Considering the diverse effects of stress in this and other studies, it appears that the type of stress and the magnitude of its appraisal determine its interactions with the pain system.

  4. [Chronic postoperative pain].

    PubMed

    Cachemaille, Matthieu; Blanc, Catherine

    2016-06-22

    Chronic postoperative pain remains a frequent pathology whose global impact approximates 20 and 30% and accounts for 20% of the consultations in a pain center. Risk factors consider firstly each patient's feature and comorbidity and also different surgical procedures with their technical approach. Neuropathic pain compared to nociceptive pain is a great component in the postoperative period and needs to be recognized by specific tests (DN4). Pain prevention involves risk factors' detection, appropriate anesthetic support and effective postoperative pain management. Treatment is based on the type of pain and includes a multimodal analgesia with interventional pain therapy.

  5. Pain and musculoskeletal pain syndromes in adolescents.

    PubMed

    Zapata, Aura Ligia; Moraes, Ana Julia Pantoja; Leone, Claudio; Doria-Filho, Ulysses; Silva, Clovis Artur Almeida

    2006-06-01

    The presence of musculoskeletal pain was evaluated in adolescents. Pain was reported by 40% of respondents, benign joint hypermobility syndrome by 10%, myofascial syndrome by 5%, tendonitis by 2%, and fibromialgia by 1%. Logistical regression analysis indicated that sex and age were predictive of pain.

  6. Fetal pain perception and pain management.

    PubMed

    Van de Velde, Marc; Jani, Jacques; De Buck, Frederik; Deprest, J

    2006-08-01

    This paper gives an overview of current science related to the concept of fetal pain. We have answered three important questions: (1) does fetal pain exist? (2) does management of fetal pain benefit the unborn child? and (3) which techniques are available to provide good fetal analgesia?

  7. Pathogenesis and clinical aspects of pain in patients with osteoporosis

    PubMed Central

    Mediati, Rocco Domenico; Vellucci, Renato; Dodaro, Lucia

    2014-01-01

    Summary Bone pain is one of the most frequent kinds of chronic pain, mainly in elderly patients. It causes a significant worsening of functional capacity and deterioration in the quality of life in people affected. Mechanisms of pain in osteoporosis are poorly known and often extrapolated by other pathologies or other experimental model. One of principal causes would be a “hyper-remodeling” of bone, that involves osteoclasts activity and pathological modifications of bone innervation. Several studies show that osteoclasts play a significant role in bone pain etiology. Pain in osteoporosis is mainly nociceptive, if it become persistent a sensitization of peripheral and central nervous system can occur, so underlining the transition to a chronic pain syndrome. Central sensitization mechanisms are complex and involve several neuromediators and receptors (Substance P, NMDA, etc.). Most common manifestations of osteoporosis are vertebral compression fractures that cause persistent pain, though to differentiate from pain originating in structures as joint or muscle. First manifestation can be an acute pain due to pathological fracture, those of hip often causes disability. Pain in osteoporosis is an important clinical challenge. Often its complications and consequences on patient quality of life are underestimated with not negligible social implications. A balanced and early multimodal pain therapy including opioids as necessary, even in cases of acute pain, improve the functional capacity of patients and helps to prevent neurological alterations that seems to contribute in significant way in causing irreversible pain chronic syndromes. PMID:25568647

  8. Chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures

    USGS Publications Warehouse

    Wang, Ning; Ingersoll, Christopher G.; Dorman, Rebecca A.; Brumbaugh, William G.; Mebane, Christopher A.; Kunz, James L.; Hardesty, Douglas K.

    2014-01-01

    Chronic toxicity of cadmium, copper, lead, or zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) was evaluated in water-only exposures started with newly hatched larvae or approximately 1-mo-old juveniles. The 20% effect concentration (EC20) for cadmium from the sturgeon tests was higher than the EC20 from the trout tests, whereas the EC20 for copper, lead, or zinc for the sturgeon were lower than those EC20s for the trout. When the EC20s from the present study were included in compiled toxicity databases for all freshwater species, species mean chronic value for white sturgeon was in a relatively low percentile of the species sensitivity distribution for copper (9th percentile) and in the middle percentile for cadmium (55th percentile), zinc (40th percentile), or lead (50th percentile). However, the species mean chronic value for rainbow trout was in a high percentile for copper, lead, and zinc (∼68th–82nd percentile), but in a low percentile for cadmium (23rd percentile). The trout EC20s for each of the 4 metals and the sturgeon EC20s for cadmium or lead were above US Environmental Protection Agency chronic ambient water quality criteria (AWQC) or Washington State chronic water quality standards (WQS), whereas the sturgeon EC20s for copper or zinc were approximately equal to or below the chronic AWQC and WQS. In addition, acute 50% effect concentrations (EC50s) for copper obtained in the first 4 d of the chronic sturgeon test were below the final acute value used to derive acute AWQC and below acute WQS for copper.

  9. Chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures.

    PubMed

    Wang, Ning; Ingersoll, Christopher G; Dorman, Rebecca A; Brumbaugh, William G; Mebane, Christopher A; Kunz, James L; Hardesty, Doug K

    2014-10-01

    Chronic toxicity of cadmium, copper, lead, or zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) was evaluated in water-only exposures started with newly hatched larvae or approximately 1-mo-old juveniles. The 20% effect concentration (EC20) for cadmium from the sturgeon tests was higher than the EC20 from the trout tests, whereas the EC20 for copper, lead, or zinc for the sturgeon were lower than those EC20s for the trout. When the EC20s from the present study were included in compiled toxicity databases for all freshwater species, species mean chronic value for white sturgeon was in a relatively low percentile of the species sensitivity distribution for copper (9th percentile) and in the middle percentile for cadmium (55th percentile), zinc (40th percentile), or lead (50th percentile). However, the species mean chronic value for rainbow trout was in a high percentile for copper, lead, and zinc (∼68th-82nd percentile), but in a low percentile for cadmium (23rd percentile). The trout EC20s for each of the 4 metals and the sturgeon EC20s for cadmium or lead were above US Environmental Protection Agency chronic ambient water quality criteria (AWQC) or Washington State chronic water quality standards (WQS), whereas the sturgeon EC20s for copper or zinc were approximately equal to or below the chronic AWQC and WQS. In addition, acute 50% effect concentrations (EC50s) for copper obtained in the first 4 d of the chronic sturgeon test were below the final acute value used to derive acute AWQC and below acute WQS for copper.

  10. Lumbosciatic pain and coagulopathies.

    PubMed

    Laus, M; Alfonso, C; Giunti, A

    1991-01-01

    Three cases of nerve compression causing lumbosciatic pain and/or cruralgia due to hematoma secondary to coagulopathies of varying etiology are described. The cases involved a multiple nerve root syndrome of the cauda equina due to extradural hematoma in coagulopathy resulting from the administration of dicumarol drugs, a neuropathy of the crural nerve caused by hematoma of the iliopsoas muscle in hemophilia B, and a neuropathy of the sciatic nerve caused by hematoma in the gluteus and thigh in coagulopathy resulting from the administration of dicumarol drugs. In all three of the cases the clinical picture resembled that of lumbar disc herniation, but a careful evaluation of each patient's history, objective picture, and laboratory and radiological testing allowed us to make a correct diagnosis. Medical therapy is based on the correction of the coagulopathy by means of suitable drugs or hemoderivates. Surgical treatment is reserved for the most severe cases.

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

    PubMed

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

    2014-04-01

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

  12. Cerebral interactions of pain and reward and their relevance for chronic pain.

    PubMed

    Becker, Susanne; Gandhi, Wiebke; Schweinhardt, Petra

    2012-06-29

    Pain and reward are opponent, interacting processes. Such interactions are enabled by neuroanatomical and neurochemical overlaps of brain systems that process pain and reward. Cerebral processing of hedonic ('liking') and motivational ('wanting') aspects of reward can be separated: the orbitofrontal cortex and opioids play an important role for the hedonic experience, and the ventral striatum and dopamine predominantly process motivation for reward. Supported by neuroimaging studies, we present here the hypothesis that the orbitofrontal cortex and opioids are responsible for pain modulation by hedonic experience, while the ventral striatum and dopamine mediate motivational effects on pain. A rewarding stimulus that appears to be particularly important in the context of pain is pain relief. Further, reward, including pain relief, leads to operant learning, which can affect pain sensitivity. Indirect evidence points at brain mechanisms that might underlie pain relief as a reward and related operant learning but studies are scarce. Investigating the cerebral systems underlying pain-reward interactions as well as related operant learning holds the potential of better understanding mechanisms that contribute to the development and maintenance of chronic pain, as detailed in the last section of this review.

  13. [Postoperative pain in craniotomy].

    PubMed

    Peón, Andréa Ungaro; Diccini, Solange

    2005-01-01

    In the postoperative period, 47% to 75% of the patients report some degree of pain. This study aimed to evaluate pain in the pre and postoperative period of patients submitted to craniotomy. This prospective research was carried out at the neurosurgery unit of a large Brazilian hospital. For a quantitative evaluation of pain, the verbal numeric 0-10 rating scale was used. Forty patients with a mean age of 36 years were evaluated. In the preoperative period, 34 (85%) patients indicated headache as the main cause of pain. In the postoperative period, 37 (93%) patients complained of pain while three (7%) reported absence of pain. Pain peaks were observed on the 2nd postoperative day, when 12 (32%) of the patients reported severe pain and 10 (27%) moderate pain. Absence of severe pain occurred after the 8th postoperative day. It was concluded that protocols of analgesia in craniotomy are needed, such as training nurses to better evaluate and handle pain.

  14. Facts and Figures on Pain

    MedlinePlus

    ... Room Position Statements AAPM Facts and Figures on Pain Overview What is Chronic Pain? Incidence of Pain, ... of them. Back to Top What is Chronic Pain? While acute pain is a normal sensation triggered ...

  15. Back pain - returning to work

    MedlinePlus

    Nonspecific back pain - work; Backache - work; Lumbar pain - work; Pain - back - chronic; Low back pain - work; Lumbago - work ... Exercise helps to prevent future back pain: Exercise a little ... keep your heart healthy and your muscles strong. If walking is ...

  16. Managing Chemotherapy Side Effects: Pain

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If you ... to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each day, ...

  17. Modeling Aeolian Transport of Contaminated Sediments at Los Alamos National Laboratory, Technical Area 54, Area G: Sensitivities to Succession, Disturbance, and Future Climate

    SciTech Connect

    Whicker, Jeffrey J.; Kirchner, Thomas B.; Breshears, David D.; Field, Jason P.

    2012-03-27

    The Technical Area 54 (TA-54) Area G disposal facility is used for the disposal of radioactive waste at Los Alamos National Laboratory (LANL). U.S. Department of Energy (DOE) Order 435.1 (DOE, 2001) requires that radioactive waste be managed in a manner that protects public health and safety and the environment. In compliance with that requirement, DOE field sites must prepare and maintain site-specific radiological performance assessments for facilities that receive waste after September 26, 1988. Sites are also required to conduct composite analyses for facilities that receive waste after this date; these analyses account for the cumulative impacts of all waste that has been (and will be) disposed of at the facilities and other sources of radioactive material that may interact with these facilities. LANL issued Revision 4 of the Area G performance assessment and composite analysis in 2008. In support of those analyses, vertical and horizontal sediment flux data were collected at two analog sites, each with different dominant vegetation characteristics, and used to estimate rates of vertical resuspension and wind erosion for Area G. The results of that investigation indicated that there was no net loss of soil at the disposal site due to wind erosion, and suggested minimal impacts of wind on the long-term performance of the facility. However, that study did not evaluate the potential for contaminant transport caused by the horizontal movement of soil particles over long time frames. Since that time, additional field data have been collected to estimate wind threshold velocities for initiating sediment transport due to saltation and rates of sediment transport once those thresholds are reached. Data such as these have been used in the development of the Vegetation Modified Transport (VMTran) model. This model is designed to estimate patterns and long-term rates of contaminant redistribution caused by winds at the site, taking into account the impacts of plant

  18. Lower-Order Pain-Related Constructs are More Predictive of Cold Pressor Pain Ratings than Higher-Order Personality Traits

    PubMed Central

    Lee, Jennifer E; Watson, David; Frey Law, Laura A

    2010-01-01

    Pain is a debilitating condition affecting millions each year, yet what predisposes certain individuals to be more sensitive to pain remains relatively unknown. Several psychological factors have been associated with pain perception, but the structural relations between multiple higher- and lower-order constructs and pain are not well understood. Thus, we aimed to examine the associations between pain perception using the cold pressor task (CPT), higher-order personality traits (neuroticism, negative affectivity, trait anxiety, extraversion, positive affectivity, psychoticism), and lower-order pain-related psychological constructs (pain catastrophizing [pre- and post], fear of pain, anxiety sensitivity, somatosensory amplification, hypochondriasis) in 66 pain-free adults. Factor analysis revealed three latent psychological variables: pain- or body-sensitivity, negative affect/neuroticism, and positive affect/extraversion. Similarly, pain responses factored into three domains: intensity, quality, and tolerance. Regression and correlation analyses demonstrated 1) all the lower-order pain constructs (fear, catastrophizing, and hypochondriasis) are related through a single underlying latent factor, that is partially related to the higher-order negative-valence personality traits; 2) pain- or body-sensitivity was more strongly predictive of pain quality than higher-order traits; and 3) the form of pain assessment is important – only qualitative pain ratings were significantly predicted by the psychological factors. Perspective: Consistent with the biopsychosocial model, these results suggest multiple pain-related psychological measures likely assess a common underlying factor, which is more predictive of qualitative than intensity pain ratings. This information may be useful for the development and advancement of pain assessments and treatments while considering the multidimensional nature of pain. PMID:20356801

  19. Craniofacial muscle pain: review of mechanisms and clinical manifestations.

    PubMed

    Svensson, P; Graven-Nielsen, T

    2001-01-01

    Epidemiologic surveys of temporomandibular disorders (TMD) have demonstrated that a considerable proportion of the population--up to 5% or 6%--will experience persistent pain severe enough to seek treatment. Unfortunately, the current diagnostic classification of craniofacial muscle pain is based on descriptions of signs and symptoms rather than on knowledge of pain mechanisms. Furthermore, the pathophysiology and etiology of craniofacial muscle pain are not known in sufficient detail to allow causal treatment. Many hypotheses have been proposed to explain cause-effect relationships; however, it is still uncertain what may be the cause of muscle pain and what is the effect of muscle pain. This article reviews the literature in which craniofacial muscle pain has been induced by experimental techniques in animals and human volunteers and in which the effects on somatosensory and motor function have been assessed under standardized conditions. This information is compared to the clinical correlates, which can be derived from the numerous cross-sectional studies in patients with craniofacial muscle pain. The experimental literature clearly indicates that muscle pain has significant effects on both somatosensory and craniofacial motor function. Typical somatosensory manifestations of experimental muscle pain are referred pain and increased sensitivity of homotopic areas. The craniofacial motor function is inhibited mainly during experimental muscle pain, but phase-dependent excitation is also found during mastication to reduce the amplitude and velocity of jaw movements. The underlying neurobiologic mechanisms probably involve varying combinations of sensitization of peripheral afferents, hyperexcitability of central neurons, and imbalance in descending pain modulatory systems. Reflex circuits in the brain stem seem important for the adjustment of sensorimotor function in the presence of craniofacial pain. Changes in somatosensory and motor function may therefore be

  20. Pressure-induced referred pain is expanded by persistent soreness.

    PubMed

    Doménech-García, V; Palsson, T S; Herrero, P; Graven-Nielsen, T

    2016-05-01

    Several chronic pain conditions are accompanied with enlarged referred pain areas. This study investigated a novel method for assessing referred pain. In 20 healthy subjects, pressure pain thresholds (PPTs) were recorded and pressure stimuli (120% PPT) were applied bilaterally for 5 and 60 seconds at the infraspinatus muscle to induce local and referred pain. Moreover, PPTs were measured bilaterally at the shoulder, neck, and leg before, during, and after hypertonic saline-induced referred pain in the dominant infraspinatus muscle. The pressure and saline-induced pain areas were assessed on drawings. Subsequently, delayed onset muscle soreness was induced using eccentric exercise of the dominant infraspinatus muscle. The day-1 assessments were repeated the following day (day 2). Suprathreshold pressure stimulations and saline injections into the infraspinatus muscle caused referred pain to the frontal aspect of the shoulder/arm in all subjects. The 60-second pressure stimulation caused larger referred pain areas compared with the 5-second stimulation (P < 0.01). Compared with pressure stimulation, the saline-induced referred pain area was larger (P < 0.02). After saline-induced pain, the PPTs at the infraspinatus and supraspinatus muscles were reduced (P < 0.05), and the 5-second pressure-induced referred pain area was larger than baseline. Pressure pain thresholds at the infraspinatus and supraspinatus muscles were reduced at day 2 in the delayed onset muscle soreness side (P < 0.05). Compared with day 1, larger pressure and saline-induced referred pain areas were observed on day 2 (P < 0.05). Referred pain to the shoulder/arm was consistently induced and enlarged after 1 day of muscle soreness, indicating that the referred pain area may be a sensitive biomarker for sensitization of the pain system.

  1. The Biochemical Origin of Pain – Proposing a new law of Pain: The origin of all Pain is Inflammation and the Inflammatory Response PART 1 of 3 – A unifying law of pain

    PubMed Central

    2009-01-01

    We are proposing a unifying theory or law of pain, which states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing a re-classification and treatment of pain syndromes based upon their inflammatory profile. Treatment of pain syndromes should be based on these principles: Determination of the inflammatory profile of the pain syndromeInhibition or suppression of production of the appropriate inflammatory mediators e.g. with inflammatory mediator blockers or surgical intervention where appropriateInhibition or suppression of neuronal afferent and efferent (motor) transmission e.g. with anti-seizure drugs or local anesthetic blocksModulation of neuronal transmission e.g. with opioid medication At the L.A. Pain Clinic, we have successfully treated a variety of pain syndromes by utilizing these principles. This theory of the biochemical origin of pain is compatible with, inclusive of, and unifies existing theories and knowledge of the mechanism of pain including the gate control theory, and theories of pre-emptive analgesia, windup and central sensitization. PMID:17240081

  2. The biochemical origin of pain--proposing a new law of pain: the origin of all pain is inflammation and the inflammatory response. Part 1 of 3--a unifying law of pain.

    PubMed

    Omoigui, Sota

    2007-01-01

    We are proposing a unifying theory or law of pain, which states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing a re-classification and treatment of pain syndromes based upon their inflammatory profile. Treatment of pain syndromes should be based on these principles: 1. Determination of the inflammatory profile of the pain syndrome; 2. Inhibition or suppression of production of the appropriate inflammatory mediators, e.g. with inflammatory mediator blockers or surgical intervention where appropriate; 3. Inhibition or suppression of neuronal afferent and efferent (motor) transmission, e.g. with anti-seizure drugs or local anesthetic blocks; 4. Modulation of neuronal transmission, e.g. with opioid medication. At the L.A. Pain Clinic, we have successfully treated a variety of pain syndromes by utilizing these principles. This theory of the biochemical origin of pain is compatible with, inclusive of, and unifies existing theories and knowledge of the mechanism of pain including the gate control theory, and theories of pre-emptive analgesia, windup and central sensitization.

  3. Pain Management Task Force

    DTIC Science & Technology

    2010-05-01

    conditions [e.g., peripheral neuropathies , lower extremity arthritis, non-specific LBP], cancer-related pain, post-surgical pain, and other acute pain...Integrative Pain Treatment Medicine .......................................................... 42 4.2.2 Osteopathic Manipulation...VHA and civilian hospitals. Visits outside of Army Medical Treatment Facilities (MTFs) were scheduled based on recommendations from Service

  4. Breakthrough cancer pain.

    PubMed

    Davies, Andrew N

    2014-06-01

    Breakthrough pain is a distinct pain state that is common in patients with cancer pain and which is associated with significant morbidity in this group of patients. The aim of this article is to highlight important journal articles relating to breakthrough pain that have been published within the last year, including a systematic review of the epidemiology of breakthrough pain, the largest-ever study of the clinical features of breakthrough pain, and a network meta-analysis of the treatment of breakthrough pain.

  5. Pain, emotion, headache.

    PubMed

    Bussone, Gennaro; Grazzi, Licia; Panerai, Alberto E

    2012-10-01

    Pain has been considered as part of a defensive strategy whose specific role is to signal an immediate active danger to the organism. This definition fits well for acute pain. It does not work well, however, for chronic pain that is maintained even in absence of an ongoing, active threat. Currently, acute and chronic pain are considered to be separate conditions. What follows is a review of the different theories about pain and its history. Different hypotheses regarding pain mechanisms are illustrated. New data emerging from scientific research on chronic pain (migraine in particular) involving innovative imaging techniques are reported and discussed.

  6. Laboratory Tests

    MedlinePlus

    Laboratory tests check a sample of your blood, urine, or body tissues. A technician or your doctor ... compare your results to results from previous tests. Laboratory tests are often part of a routine checkup ...

  7. Personality and temperament correlates of pain catastrophizing in young adolescents.

    PubMed

    Muris, Peter; Meesters, Cor; van den Hout, Anja; Wessels, Sylvia; Franken, Ingmar; Rassin, Eric

    2007-10-01

    Pain catastrophizing is generally viewed as an important cognitive factor underlying chronic pain. The present study examined personality and temperament correlates of pain catastrophizing in a sample of young adolescents (N = 132). Participants completed the Pain Catastrophizing Scale for Children, as well as scales for measuring sensitivity of the behavioral inhibition and behavioral activation systems (BIS-BAS), and various reactive and regulative temperament traits. Results demonstrated that BIS, reactive temperament traits (fear and anger-frustration), and perceptual sensitivity were positively related to pain catastrophizing, whereas regulative traits (attention control, inhibitory control) were negatively associated with this cognitive factor. Further, regression analyses demonstrated that only BIS and the temperamental traits of fear and perceptual sensitivity accounted for a unique proportion of the variance in adolescents' pain catastrophizing scores.