Ethnicity Interacts with the OPRM1 Gene in Experimental Pain Sensitivity

PubMed Central

Hastie, Barbara A.; Riley, Joseph L.; Kaplan, Lee; Herrera, Dyanne G.; Campbell, Claudia M.; Virtusio, Kathrina; Mogil, Jeffrey S.; Wallace, Margaret R.; Fillingim, Roger B.

2013-01-01

Robust inter-individual variation in pain sensitivity has been observed and recent evidence suggests that some of the variability may be genetically-mediated. Our previous data revealed significantly higher pressure pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared to those with two consensus alleles. Moreover, ethnic differences in pain sensitivity have been widely reported. Yet, little is known about the potential interactive associations of ethnicity and genotype with pain perception. This study aimed to identify ethnic differences in OPRM1 allelic associations with experimental pain responses. Two-hundred and forty-seven healthy young adults from three ethnic groups (81 African Americans; 79 non-white Hispanics; and 87 non-Hispanic whites) underwent multiple experimental pain modalities (thermal, pressure, ischemic, cold pressor). Few African Americans (7.4%) expressed the rare allele of OPRM1 compared to non-Hispanic-whites and Hispanics (28.7% vs. 27.8%, respectively). Across the entire sample, OPRM1 genotype did not significantly affect pain sensitivity. However, analysis in each ethnic group separately revealed significant genotype effects for most pain modalities among non-Hispanic-whites (ps<0.05) but not Hispanics or African Americans. The G allele was associated with decreased pain sensitivity among whites only; a trend in the opposite direction emerged in Hispanics. The reasons for this dichotomy are unclear but may involve ethnic differences in haplotypic structure or A118G may be a tag-SNP linked to other functional polymorphisms. These findings demonstrate an ethnic-dependent association of OPRM1 genotype with pain sensitivity. Additional research is warranted to uncover the mechanisms influencing these relationships. PMID:22717102

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

PubMed

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

2015-02-01

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

Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis.

PubMed

Olesen, Anne E; Nielsen, Lecia M; Feddersen, Søren; Erlenwein, Joachim; Petzke, Frank; Przemeck, Michael; Christrup, Lona L; Drewes, Asbjørn M

2018-06-01

Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu, kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned pain modulation effect, and (4) pressure stimulation at the tibia in both the affected and the unaffected leg. Ninety-two patients (mean age 66 years) with unilateral hip osteoarthritis were included in the study. Carriage of the OPRM1 rs589046T allele was found to be associated with increased pain ratings during hip rotation (P = 0.04) and increased conditioned pain modulation (P = 0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with an increased pain detection threshold to contact heat stimulation (P = 0.001). No other associations were found (all P > 0.05). Results from the present study suggest that, in patients with hip osteoarthritis, genetic variants in OPRM1 and OPRD1 may contribute to the pain phenotype. © 2017 World Institute of Pain.

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

PubMed Central

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

2016-01-01

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

Individual modulation of pain sensitivity under stress.

PubMed

Reinhardt, Tatyana; Kleindienst, Nikolaus; Treede, Rolf-Detlef; Bohus, Martin; Schmahl, Christian

2013-05-01

Stress has a strong influence on pain sensitivity. However, the direction of this influence is unclear. Recent studies reported both decreased and increased pain sensitivities under stress, and one hypothesis is that interindividual differences account for these differences. The aim of our study was to investigate the effect of stress on individual pain sensitivity in a relatively large female sample. Eighty female participants were included. Pain thresholds and temporal summation of pain were tested before and after stress, which was induced by the Mannheim Multicomponent Stress Test. In an independent sample of 20 women, correlation coefficients between 0.45 and 0.89 indicated relatively high test-retest reliability for pain measurements. On average, there were significant differences between pain thresholds under non-stress and stress conditions, indicating an increased sensitivity to pain under stress. No significant differences between non-stress and stress conditions were found for temporal summation of pain. On an individual basis, both decreased and increased pain sensitivities under stress conditions based on Jacobson's criteria for reliable change were observed. Furthermore, we found significant negative associations between pain sensitivity under non-stress conditions and individual change of pain sensitivity under stress. Participants with relatively high pain sensitivity under non-stress conditions became less sensitive under stress and vice versa. These findings support the view that pain sensitivity under stress shows large interindividual variability, and point to a possible dichotomy of altered pain sensitivity under stress. Wiley Periodicals, Inc.

A cross-sectional study of pain sensitivity, disease-activity assessment, mental health, and fibromyalgia status in rheumatoid arthritis.

PubMed

Joharatnam, Nalinie; McWilliams, Daniel F; Wilson, Deborah; Wheeler, Maggie; Pande, Ira; Walsh, David A

2015-01-20

Pain remains the most important problem for people with rheumatoid arthritis (RA). Active inflammatory disease contributes to pain, but pain due to non-inflammatory mechanisms can confound the assessment of disease activity. We hypothesize that augmented pain processing, fibromyalgic features, poorer mental health, and patient-reported 28-joint disease activity score (DAS28) components are associated in RA. In total, 50 people with stable, long-standing RA recruited from a rheumatology outpatient clinic were assessed for pain-pressure thresholds (PPTs) at three separate sites (knee, tibia, and sternum), DAS28, fibromyalgia, and mental health status. Multivariable analysis was performed to assess the association between PPT and DAS28 components, DAS28-P (the proportion of DAS28 derived from the patient-reported components of visual analogue score and tender joint count), or fibromyalgia status. More-sensitive PPTs at sites over or distant from joints were each associated with greater reported pain, higher patient-reported DAS28 components, and poorer mental health. A high proportion of participants (48%) satisfied classification criteria for fibromyalgia, and fibromyalgia classification or characteristics were each associated with more sensitive PPTs, higher patient-reported DAS28 components, and poorer mental health. Widespread sensitivity to pressure-induced pain, a high prevalence of fibromyalgic features, higher patient-reported DAS28 components, and poorer mental health are all linked in established RA. The increased sensitivity at nonjoint sites (sternum and anterior tibia), as well as over joints, indicates that central mechanisms may contribute to pain sensitivity in RA. The contribution of patient-reported components to high DAS28 should inform decisions on disease-modifying or pain-management approaches in the treatment of RA when inflammation may be well controlled.

Brain imaging of pain sensitization in patients with knee osteoarthritis.

PubMed

Pujol, Jesus; Martínez-Vilavella, Gerard; Llorente-Onaindia, Jone; Harrison, Ben J; López-Solà, Marina; López-Ruiz, Marina; Blanco-Hinojo, Laura; Benito, Pere; Deus, Joan; Monfort, Jordi

2017-09-01

A relevant aspect in osteoarthritic pain is neural sensitization. This phenomenon involves augmented responsiveness to painful stimulation and may entail a clinically worse prognosis. We used functional magnetic resonance imaging (fMRI) to study pain sensitization in patients with knee osteoarthritis. Sixty patients were recruited and pain sensitization was clinically defined on the basis of regional spreading of pain (spreading sensitization) and increased pain response to repeated stimulation (temporal summation). Functional magnetic resonance imaging testing involved assessing brain responses to both pressure and heat stimulation. Thirty-three patients (55%) showed regional pain spreading (simple sensitization) and 19 patients (32%) showed both regional spreading and temporal summation. Sensitized patients were more commonly women. Direct painful pressure stimulation of the joint (articular interline) robustly activated all of the neural elements typically involved in pain perception, but did not differentiate sensitized and nonsensitized patients. Painful pressure stimulation on the anterior tibial surface (sensitized site) evoked greater activation in sensitized patients in regions typically involved in pain and also beyond these regions, extending to the auditory, visual, and ventral sensorimotor cortices. Painful heat stimulation of the volar forearm did not discriminate the sensitization phenomenon. Results confirm the high prevalence of pain sensitization secondary to knee osteoarthritis. Relevantly, the sensitization phenomenon was associated with neural changes extending beyond strict pain-processing regions with enhancement of activity in general sensory, nonnociceptive brain areas. This effect is in contrast to the changes previously identified in primary pain sensitization in fibromyalgia patients presenting with a weakening of the general sensory integration.

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

PubMed

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

2016-10-01

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

Subjective Sleep Quality Deteriorates Prior to Development of Painful Temporomandibular Disorder

PubMed Central

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

2016-01-01

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

Predictors and Moderators of Post-traumatic Stress Disorder: An Investigation of Anxiety Sensitivity and Resilience in Individuals with Chronic Pain.

PubMed

Lies, July; Lau, Shi Ting; Jones, Lester E; Jensen, Mark P; Tan, Gabriel

2017-03-01

Anxiety sensitivity has been proposed as a psychological vulnerability factor for post-traumatic stress disorder (PTSD). Studies have also supported the protective role of resilience for overcoming the negative effects of trauma exposure. Given the linkages between anxiety sensitivity, resilience, trauma exposure and post-traumatic stress, this study explored the potential moderating roles of anxiety sensitivity and resilience on the association between trauma history and PTSD symptoms in a sample of individuals with chronic pain. A total of 100 patients with chronic pain were recruited from a large public hospital. Patients who had pain lasting for more than 3 months and a pain intensity rating of at least 4/10 were included. The study participants were administered measures of PTSD symptoms (PTSD Checklist - Civilian Version), resilience (Brief Resilient Coping Scale) and anxiety sensitivity (Anxiety Sensitivity Index). An analysis of outcome measures indicated that anxiety sensitivity and resilience were independently associated with PTSD symptoms, where βs were 0.57 and -0.23, respectively. The relationship between trauma and PTSD symptom severity was also moderated by anxiety sensitivity. Trauma history was associated with higher PTSD symptom severity only in those with high anxiety sensitivity. However, contrary to the hypotheses, resilience did not serve as a moderator. There are potential benefits of PTSD interventions that increase resilience and decrease anxiety sensitivity in individuals with chronic pain, especially for those who have experienced a traumatic event. Given that the presence of PTSD symptomatology in chronic pain populations negatively impact patient well-being, it would be important for clinicians to assess, monitor and treat PTSD in individuals with chronic pain.

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

PubMed

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

2014-03-01

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

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

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

PubMed

Becker, Johanna; Reist, Martin; Steiner, Adrian

2014-04-01

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

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; Haythornthwaite JA. Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder. SLEEP 2009;32(6):779–790. PMID:19544755

Gender expression, sexual orientation and pain sensitivity in women.

PubMed

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

2014-01-01

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

Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.

PubMed

Willen, Shaina M; Rodeghier, Mark; Strunk, Robert C; Bacharier, Leonard B; Rosen, Carol L; Kirkham, Fenella J; DeBaun, Michael R; Cohen, Robyn T

2018-02-01

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P < 0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P = 0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA. © 2018 John Wiley & Sons Ltd.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2016-10-01

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

Sex differences in how social networks and relationship quality influence experimental pain sensitivity.

PubMed

Vigil, Jacob M; Rowell, Lauren N; Chouteau, Simone; Chavez, Alexandre; Jaramillo, Elisa; Neal, Michael; Waid, David

2013-01-01

This is the first study to examine how both structural and functional components of individuals' social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one's significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual's social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed.

Sex Differences in How Social Networks and Relationship Quality Influence Experimental Pain Sensitivity

PubMed Central

Vigil, Jacob M.; Rowell, Lauren N.; Chouteau, Simone; Chavez, Alexandre; Jaramillo, Elisa; Neal, Michael; Waid, David

2013-01-01

This is the first study to examine how both structural and functional components of individuals’ social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one’s significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual’s social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed. PMID:24223836

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

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

PubMed

Defrin, Ruth; Schreiber, Shaul; Ginzburg, Karni

2015-10-01

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

Gender expression, sexual orientation and pain sensitivity in women

PubMed Central

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

2014-01-01

BACKGROUND: Despite a growing body of literature investigating sex differences with regard to pain, surprisingly little research has been conducted on the influence of various aspects of self-identity, including gender expression and sexual orientation, on pain sensitivity within each sex, particularly among women. In men, dispositional femininity is linked to greater clinical pain and trait masculinity is associated with higher pain thresholds. OBJECTIVES: To examine whether gender expression and sexual orientation are associated with within-sex differences in ischemic pain sensitivity in healthy young women. METHODS: A convenience sample of 172 females (mean age 21.4 years; range 18 to 30 years of age; 56.0% white, 89% heterosexual) performed an ischemic pain task in counterbalanced order. Desired levels of dispositional femininity for a preferred romantic partner and self-described levels of personal dispositional femininity were measured. RESULTS: Compared with heterosexual women, lesbian and bisexual women reported lower pain intensity ratings early in the discomfort task. Irrespective of sexual orientation, attraction to more feminine romantic partners and dispositional masculinity were correlated with lower pain intensity, and with higher pain thresholds and tolerance levels. DISCUSSION: These preliminary findings suggest that within-sex differences in sexual orientation and other aspects of identity, irrespective of biological sex, may be important to consider when examining experimental pain performance and clinical pain experiences. CONCLUSION: Larger investigations of the psychophysiological relationships among sexual orientation, gender expression and pain sensitivity are warranted. These findings may have implications for differences in clinical pain sensitivity of lesbian and bisexual women compared with heterosexual women. PMID:24575419

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

PubMed Central

Staud, Roland

2009-01-01

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

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

PubMed Central

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

2016-01-01

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

Understanding the role of injury/illness sensitivity and anxiety sensitivity in (automatic) pain processing: an examination using the extrinsic affective simon task.

PubMed

Vancleef, Linda M G; Peters, Madelon L; Gilissen, Susan M P; De Jong, Peter J

2007-07-01

Three fundamental fears are assumed to underlie psychopathology: Anxiety Sensitivity (AS), Injury/illness sensitivity (IS), and Fear of Negative Evaluation (FNE). Both AS and IS may form risk factors for the development and exacerbation of chronic pain. The current research examines the relation between these fears and automatic threat appraisal for pain-related stimuli. Study 1 (n=48) additionally examined content-specific associations of AS and FNE with the automatic threat appraisal of, respectively, panic and social evaluative cues. Study 2 (n=60) additionally focused on the association of IS and AS with the engagement in health protecting behavior, and the use of health care services. Both studies found evidence for an automatic threat appraisal of aversive stimuli. Study 2 demonstrated a positive association between the automatic threat appraisal for pain-related stimuli and individuals' IS levels. IS was found to be the single best predictor of the tendency to engage in health protecting behavior, whereas AS was the single best predictor of the reported use of health care services. This study contributes to the field of knowledge on putative risk factors for chronic pain. Results demonstrate an automatic threat appraisal toward pain-related stimuli that is related to vulnerability traits for pain. This automatic threat appraisal might initiate relatively spontaneous (nonstrategic) pain-maintaining behavioral responses.

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

PubMed

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

2017-02-01

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

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

PubMed

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

2016-10-01

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

Multiple Levels of Suffering

PubMed Central

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

2016-01-01

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

Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

PubMed

Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

2013-10-01

Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-07-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2012-12-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2011-08-01

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

Pain Processing after Social Exclusion and Its Relation to Rejection Sensitivity in Borderline Personality Disorder

PubMed Central

Bungert, Melanie; Koppe, Georgia; Niedtfeld, Inga; Vollstädt-Klein, Sabine; Schmahl, Christian

2015-01-01

Objective There is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that “social pain,” as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity. Method Twenty unmedicated female BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game (cyberball), with the conditions for exclusion, inclusion, and a control condition with predefined game rules. Each cyberball block was followed by a temperature stimulus (with a subjective pain intensity of 60% in half the cases). The cerebral responses were measured by functional magnetic resonance imaging. The Adult Rejection Sensitivity Questionnaire was used to assess rejection sensitivity. Results Higher temperature heat stimuli had to be applied to BPD patients relative to HCs to reach a comparable subjective experience of painfulness in both groups, which suggested a general hyposensitivity to pain in BPD patients. Social exclusion led to a subjectively reported hypersensitivity to physical pain in both groups that was accompanied by an enhanced activation in the anterior insula and the thalamus. In BPD, physical pain processing after exclusion was additionally linked to enhanced posterior insula activation. After inclusion, BPD patients showed reduced amygdala activation during pain in comparison with HC. In BPD patients, higher rejection sensitivity was associated with lower activation differences during pain processing following social exclusion and inclusion in the insula and in the amygdala. Discussion Despite the similar behavioral effects in both groups, BPD patients differed from HC in their neural processing of physical pain depending on the preceding social situation. Rejection sensitivity further modulated the impact of social exclusion on neural pain processing in BPD, but not in healthy controls. PMID:26241850

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

PubMed

Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Association Between Borderline Personality Features and Temporal Summation of Second Pain: A Cross-Sectional Study.

PubMed

You, Dokyoung S; Meagher, Mary W

2017-01-01

Individuals with greater borderline personality features may be vulnerable to chronic pain. Because pain is an unpleasant sensory and emotional experience, affect dysregulation as the core personality feature may be linked to pain hypersensitivity. Studies have found that greater borderline features are associated with increased intensity in clinical and experimental pain, and that depression mediates this increase. The current study further examined the association between borderline features and heat pain sensitivity, the contribution of affect dysregulation and the other borderline personality factors (identity problems, negative relationships, self-harming/impulsivity) to the association, and depression as a mediator. Additionally, we examined whether blunted sympathetic responses mediate the association between borderline features and temporal summation of second pain (TSSP). Thermal pain threshold, thermal TSSP and aftersensations pain were assessed in 79 healthy individuals with varying degrees of borderline features. TSSP is a proxy measure for central sensitization and refers to the gradual increase in pain to repeated nociceptive stimuli. A regression analysis showed that greater borderline features predicted greater TSSP (β = .22, p = .050, R 2 = .05). Borderline features were unrelated to pain threshold and TSSP decay. A stepwise regression showed greater TSSP in individuals with greater borderline features was accounted for by the negative relationships factor rather than the affect dysregulation factor. The results of mediational analyses showed depression and blunted sympathetic skin conductance responses mediated the positive association between TSSP and borderline features.

Somatic syndromes and chronic pain in women with overactive bladder

PubMed Central

Reynolds, W. Stuart; Mock, Stephen; Zhang, Xuechao; Kaufman, Melissa; Wein, Alan; Bruehl, Stephen; Dmochowski, Roger

2016-01-01

Aims Mechanisms underlying pain perception and afferent hypersensitivity, such as central sensitization, may impact overactive bladder (OAB) symptoms. However, little is known about associations between OAB symptom severity, pain experience, and presence of comorbid chronic pain syndromes. This study examined relationships between OAB symptoms, somatic symptoms, and specific chronic pain conditions in which central sensitization is believed to play a primary role, in a community-based sample of adult women with OAB Methods We recruited adult women with OAB to complete questionnaires assessing urinary symptoms, pain and somatic symptoms, and preexisting diagnoses of central sensitivity syndromes. We analyzed the effects of overall bodily pain intensity, general somatic symptoms, and diagnoses of central sensitivity syndromes on OAB symptom bother and health-related quality of life. Results Of the 116 women in this study, over half (54%) stated their urge to urinate was associated with pain, pressure, or discomfort. Participants reported a wide range of OAB symptoms and health-related quality of life. There was a significant, positive correlation between OAB symptoms and somatic symptoms as well as overall pain intensity. Only 7% of women met diagnostic criteria for fibromyalgia; yet these women demonstrated significantly increased OAB symptom burden and decreased OAB quality of life compared to those without fibromyalgia. Conclusion Women with more severe OAB symptoms reported increased general somatic symptom burden and increased overall body pain intensity, especially women with fibromyalgia. These findings suggest that attributes of pain and co-morbidity with chronic pain conditions may impact the experience of OAB symptoms for many women. PMID:27367486

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

PubMed

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

2009-11-01

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

Behavioral and molecular processing of visceral pain in the brain of mice: impact of colitis and psychological stress

PubMed Central

Jain, Piyush; Hassan, Ahmed M.; Koyani, Chintan N.; Mayerhofer, Raphaela; Reichmann, Florian; Farzi, Aitak; Schuligoi, Rufina; Malle, Ernst; Holzer, Peter

2015-01-01

Gastrointestinal disorders with abdominal pain are associated with central sensitization and psychopathologies that are often exacerbated by stress. Here we investigated the impact of colitis induced by dextran sulfate sodium (DSS) and repeated water avoidance stress (WAS) on spontaneous and nociception-related behavior and molecular signaling in the mouse brain. DSS increased the mechanical pain sensitivity of the abdominal skin while both WAS and DSS enhanced the mechanical and thermal pain sensitivity of the plantar skin. These manifestations of central sensitization were associated with augmented c-Fos expression in spinal cord, thalamus, hypothalamus, amygdala and prefrontal cortex. While WAS stimulated phosphorylation of mitogen-activated protein kinase (MAPK) p42/44, DSS activated another signaling pathway, both of which converged on c-Fos. The DSS- and WAS-induced hyperalgesia in the abdominal and plantar skin and c-Fos expression in the brain disappeared when the mice were subjected to WAS+DSS treatment. Intrarectal allyl isothiocyanate (AITC) evoked aversive behavior (freezing, reduction of locomotion and exploration) in association with p42/44 MAPK and c-Fos activation in spinal cord and brain. These effects were inhibited by morphine, which attests to their relationship with nociception. DSS and WAS exerted opposite effects on AITC-evoked p42/44 MAPK and c-Fos activation, which indicates that these transduction pathways subserve different aspects of visceral pain processing in the brain. In summary, behavioral perturbations caused by colitis and psychological stress are associated with distinct alterations in cerebral signaling. These findings provide novel perspectives on central sensitization and the sensory and emotional processing of visceral pain stimuli in the brain. PMID:26217204

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

PubMed

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

2016-03-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

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

The association of greater dispositional optimism with less endogenous pain facilitation is indirectly transmitted through lower levels of pain catastrophizing.

PubMed

Goodin, Burel R; Glover, Toni L; Sotolongo, Adriana; King, Christopher D; Sibille, Kimberly T; Herbert, Matthew S; Cruz-Almeida, Yenisel; Sanden, Shelley H; Staud, Roland; Redden, David T; Bradley, Laurence A; Fillingim, Roger B

2013-02-01

Dispositional optimism has been shown to beneficially influence various experimental and clinical pain experiences. One possibility that may account for decreased pain sensitivity among individuals who report greater dispositional optimism is less use of maladaptive coping strategies such as pain catastrophizing, a negative cognitive/affective response to pain. An association between dispositional optimism and conditioned pain modulation, a measure of endogenous pain inhibition, has previously been reported. However, it remains to be determined whether dispositional optimism is also associated with temporal summation (TS), a measure of endogenous pain facilitation. The current study examined whether pain catastrophizing mediated the association between dispositional optimism and TS among 140 older, community-dwelling adults with symptomatic knee osteoarthritis. Individuals completed measures of dispositional optimism and pain catastrophizing. TS was then assessed using a tailored heat pain stimulus on the forearm. Greater dispositional optimism was significantly related to lower levels of pain catastrophizing and TS. Bootstrapped confidence intervals revealed that less pain catastrophizing was a significant mediator of the relation between greater dispositional optimism and diminished TS. These findings support the primary role of personality characteristics such as dispositional optimism in the modulation of pain outcomes by abatement of endogenous pain facilitation and less use of catastrophizing. Results from this study further support the body of evidence that attests to the beneficial effects of positive personality traits on pain sensitivity and pain processing. Further, this study identified diminished pain catastrophizing as an important mechanism explaining the inverse relation between dispositional optimism and endogenous pain facilitation. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

An increased response to experimental muscle pain is related to psychological status in women with chronic non-traumatic neck-shoulder pain

PubMed Central

2011-01-01

Background Neck-shoulder pain conditions, e.g., chronic trapezius myalgia, have been associated with sensory disturbances such as increased sensitivity to experimentally induced pain. This study investigated pain sensitivity in terms of bilateral pressure pain thresholds over the trapezius and tibialis anterior muscles and pain responses after a unilateral hypertonic saline infusion into the right legs tibialis anterior muscle and related those parameters to intensity and area size of the clinical pain and to psychological factors (sleeping problems, depression, anxiety, catastrophizing and fear-avoidance). Methods Nineteen women with chronic non-traumatic neck-shoulder pain but without simultaneous anatomically widespread clinical pain (NSP) and 30 age-matched pain-free female control subjects (CON) participated in the study. Results NSP had lower pressure pain thresholds over the trapezius and over the tibialis anterior muscles and experienced hypertonic saline-evoked pain in the tibialis anterior muscle to be significantly more intense and locally more widespread than CON. More intense symptoms of anxiety and depression together with a higher disability level were associated with increased pain responses to experimental pain induction and a larger area size of the clinical neck-shoulder pain at its worst. Conclusion These results indicate that central mechanisms e.g., central sensitization and altered descending control, are involved in chronic neck-shoulder pain since sensory hypersensitivity was found in areas distant to the site of clinical pain. Psychological status was found to interact with the perception, intensity, duration and distribution of induced pain (hypertonic saline) together with the spreading of clinical pain. The duration and intensity of pain correlated negatively with pressure pain thresholds. PMID:21992460

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

PubMed

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

2014-05-01

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

Relationship of Pain and Ancestry in African American Women

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-01-01

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

Central Sensitization and Perceived Indoor Climate among Workers with Chronic Upper-Limb Pain: Cross-Sectional Study

PubMed Central

Jakobsen, Markus D.; Jay, Kenneth; Persson, Roger; Andersen, Lars L.

2015-01-01

Monitoring of indoor climate is an essential part of occupational health and safety. While questionnaires are commonly used for surveillance, not all workers may perceive an identical indoor climate similarly. The aim of this study was to evaluate perceived indoor climate among workers with chronic pain compared with pain-free colleagues and to determine the influence of central sensitization on this perception. Eighty-two male slaughterhouse workers, 49 with upper-limb chronic pain and 33 pain-free controls, replied to a questionnaire with 13 items of indoor climate complaints. Pressure pain threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain-free controls (1.8 [95% CI: 1.3–2.3] versus 0.9 [0.4–1.5], resp.). PPT of the nonpainful leg muscle was negatively associated with the number of complaints. Workers with chronic pain reported more indoor climate complaints than pain-free controls despite similar actual indoor climate. Previous studies that did not account for musculoskeletal pain in questionnaire assessment of indoor climate may be biased. Central sensitization likely explains the present findings. PMID:26425368

Myofascial trigger points: spontaneous electrical activity and its consequences for pain induction and propagation

PubMed Central

2011-01-01

Active myofascial trigger points are one of the major peripheral pain generators for regional and generalized musculoskeletal pain conditions. Myofascial trigger points are also the targets for acupuncture and/or dry needling therapies. Recent evidence in the understanding of the pathophysiology of myofascial trigger points supports The Integrated Hypothesis for the trigger point formation; however unanswered questions remain. Current evidence shows that spontaneous electrical activity at myofascial trigger point originates from the extrafusal motor endplate. The spontaneous electrical activity represents focal muscle fiber contraction and/or muscle cramp potentials depending on trigger point sensitivity. Local pain and tenderness at myofascial trigger points are largely due to nociceptor sensitization with a lesser contribution from non-nociceptor sensitization. Nociceptor and non-nociceptor sensitization at myofascial trigger points may be part of the process of muscle ischemia associated with sustained focal muscle contraction and/or muscle cramps. Referred pain is dependent on the sensitivity of myofascial trigger points. Active myofascial trigger points may play an important role in the transition from localized pain to generalized pain conditions via the enhanced central sensitization, decreased descending inhibition and dysfunctional motor control strategy. PMID:21439050

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

PubMed Central

2014-01-01

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

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

PubMed

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

2014-03-05

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

Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: a MAPP Research Network study.

PubMed

Schrepf, Andrew; Williams, David A; Gallop, Robert; Naliboff, Bruce; Basu, Neil; Kaplan, Chelsea; Harper, Daniel E; Landis, Richard; Clemens, J Quentin; Strachan, Eric; Griffith, James W; Afari, Niloofar; Hassett, Afton; Pontari, Michel A; Clauw, Daniel J; Harte, Steven E

2018-05-28

Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This 'centralized pain' phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here we used three cohorts, including patients with Urologic Chronic Pelvic Pain Syndrome (UCPPS), a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified two general factors in all three cohorts, one characterized by a broad increased sensitivity to internal somatic sensations and environmental stimuli, and diffuse pain, termed Generalized Sensory Sensitivity (GSS), and one characterized by constitutional symptoms - Sleep, Pain, Affect, Cognition, Energy (SPACE). Longitudinal analyses in the UCPPS cohort found the same two factor structure at month six and one year, suggesting that the two factor structure is reproducible over time. In secondary analyses we found that GSS particularly is associated with the presence of comorbid COPCs, while SPACE shows modest associations with measures of disability and urinary symptoms. These factors may represent important and distinct continuum of symptoms that are indicative of the centralized pain phenotype at high levels. Future research of COPCs should accommodate the measurement of each factor.

Genomic Methods for Clinical and Translational Pain Research

PubMed Central

Wang, Dan; Kim, Hyungsuk; Wang, Xiao-Min; Dionne, Raymond

2012-01-01

Pain is a complex sensory experience for which the molecular mechanisms are yet to be fully elucidated. Individual differences in pain sensitivity are mediated by a complex network of multiple gene polymorphisms, physiological and psychological processes, and environmental factors. Here, we present the methods for applying unbiased molecular-genetic approaches, genome-wide association study (GWAS), and global gene expression analysis, to help better understand the molecular basis of pain sensitivity in humans and variable responses to analgesic drugs. PMID:22351080

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2015-01-01

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

The lateral prefrontal cortex mediates the hyperalgesic effects of negative cognitions in chronic pain patients.

PubMed

Loggia, Marco L; Berna, Chantal; Kim, Jieun; Cahalan, Christine M; Martel, Marc-Olivier; Gollub, Randy L; Wasan, Ajay D; Napadow, Vitaly; Edwards, Robert R

2015-08-01

Although high levels of negative affect and cognitions have been associated with greater pain sensitivity in chronic pain conditions, the neural mechanisms mediating the hyperalgesic effect of psychological factors in patients with pain disorders are largely unknown. In this cross-sectional study, we hypothesized that 1) catastrophizing modulates brain responses to pain anticipation and 2) anticipatory brain activity mediates the hyperalgesic effect of different levels of catastrophizing in fibromyalgia (FM) patients. Using functional magnetic resonance imaging, we scanned the brains of 31 FM patients exposed to visual cues anticipating the onset of moderately intense deep-tissue pain stimuli. Our results indicated the existence of a negative association between catastrophizing and pain-anticipatory brain activity, including in the right lateral prefrontal cortex. A bootstrapped mediation analysis revealed that pain-anticipatory activity in the lateral prefrontal cortex mediates the association between catastrophizing and pain sensitivity. These findings highlight the role of the lateral prefrontal cortex in the pathophysiology of FM-related hyperalgesia and suggest that deficits in the recruitment of pain-inhibitory brain circuitry during pain-anticipatory periods may play an important contributory role in the association between various degrees of widespread hyperalgesia in FM and levels of catastrophizing, a well-validated measure of negative cognitions and psychological distress. This article highlights the presence of alterations in pain-anticipatory brain activity in FM. These findings provide the rationale for the development of psychological or neurofeedback-based techniques aimed at modifying patients' negative affect and cognitions toward pain. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Anxiety and depressive symptoms and anxiety sensitivity in youngsters with noncardiac chest pain and benign heart murmurs.

PubMed

Lipsitz, Joshua D; Masia-Warner, Carrie; Apfel, Howard; Marans, Zvi; Hellstern, Beth; Forand, Nicholas; Levenbraun, Yosef; Fyer, Abby J

2004-12-01

Chest pain in children and adolescents is rarely associated with cardiac disease. We sought to examine psychological symptoms in youngsters with medically unexplained chest pain. We hypothesized that children and adolescents with medically unexplained chest pain would have high rates of anxiety and depressive symptoms. We assessed 65 youngsters with noncardiac chest pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self-report measures of anxiety and depressive symptoms and anxiety sensitivity. Compared with the asymptomatic benign-murmur group, youngsters with NCCP had higher levels of some anxiety symptoms and anxiety sensitivity. Differences on depressive symptoms were not significant. Though preliminary, results suggest that youngsters with chest pain may experience increased levels of some psychological symptoms. Future studies of noncardiac chest pain in youngsters should include larger samples and comprehensive diagnostic assessments as well as long-term follow-up evaluations.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Conditioned pain modulation in women with irritable bowel syndrome

USDA-ARS?s Scientific Manuscript database

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...

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

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

PubMed

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

2016-11-01

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

The Sensitivity to Change and Responsiveness of the Adult Responses to Children’s Symptoms in Children and Adolescents With Chronic Pain

PubMed Central

Alberts, Nicole; Langer, Shelby L.; Levy, Rona L.; Walker, Lynn S.; Palermo, Tonya M.

2016-01-01

Abstract Objective  To examine the sensitivity to change and responsiveness of the Adult Responses to Children’s Symptoms (ARCS) among parents of youth with chronic pain.  Methods  Participants included 330 youth (89 children aged 7–11 years, 241 children aged 12–17 years) and their parents who participated in randomized controlled trials of family-based cognitive-behavioral therapy for chronic pain. Child pain and disability, parental emotional functioning, and parental responses to child pain were assessed at baseline and posttreatment.  Results  The Protect and Monitor scales of the ARCS were sensitive to change following intervention for both developmental groups, with clinically meaningful reductions in these behaviors, thereby demonstrating responsiveness. Among the adolescent sample, greater change on some ARCS scales was associated with better parental emotional functioning and lower child pain at posttreatment.  Conclusions  Findings support the sensitivity to change and responsiveness of the Protect and Monitor scales among parents of youth with chronic pain. PMID:26493601

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

PubMed

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

2017-10-01

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

Night-shift work is associated with increased pain perception.

PubMed

Matre, Dagfinn; Knardahl, Stein; Nilsen, Kristian Bernhard

2017-05-01

Objectives The aim of the present study was to determine whether shift workers exhibit increased perception of experimentally induced pain after working night shifts. Methods The study was a paired cross-over design with two sleep conditions, after at least two nights of habitual sleep and after two consecutive night shifts at work. Fifty-three nurses in rotating shift work participated. The sensitivity to electrically induced pain, heat pain, cold pain, pressure pain and pain inhibition was determined experimentally in each sleep condition. Sleepiness and vigilance were also assessed. Results Night-shift work (NSW) increased the sensitivity to electrically induced pain and heat pain (P≤0.001). Relative to habitual sleep, electrically induced pain increased by 22.3% and heat pain increased by 26.5%. The sensitivity to cold and pressure pain did not change, changes relative to habitual sleep was <5% (P>0.5). Pain inhibition was 66.9% stronger after NSW versus after habitual sleep (P<0.001). Sleepiness (measured with the Karolinska Sleepiness Scale) increased from 4.1 after habitual sleep to 6.9 after NSW (P<0.001). Vigilance decreased after NSW, measured as a 0.03-second decrease in reaction time (P<0.005). Conclusions Changes in pain sensitivity after NSW is measurable with clinically relevant effect sizes and may be an important marker for studies comparing the physiological effects of different shift work schedules. Explanations for the differential effect on different pain modalities should be a focus for future studies.

Identification of clusters of individuals relevant to temporomandibular disorders and other chronic pain conditions: the OPPERA study

PubMed Central

Bair, Eric; Gaynor, Sheila; Slade, Gary D.; Ohrbach, Richard; Fillingim, Roger B.; Greenspan, Joel D.; Dubner, Ronald; Smith, Shad B.; Diatchenko, Luda; Maixner, William

2016-01-01

The classification of most chronic pain disorders gives emphasis to anatomical location of the pain to distinguish one disorder from the other (eg, back pain vs temporomandibular disorder [TMD]) or to define subtypes (eg, TMD myalgia vs arthralgia). However, anatomical criteria overlook etiology, potentially hampering treatment decisions. This study identified clusters of individuals using a comprehensive array of biopsychosocial measures. Data were collected from a case–control study of 1031 chronic TMD cases and 3247 TMD-free controls. Three subgroups were identified using supervised cluster analysis (referred to as the adaptive, pain-sensitive, and global symptoms clusters). Compared with the adaptive cluster, participants in the pain-sensitive cluster showed heightened sensitivity to experimental pain, and participants in the global symptoms cluster showed both greater pain sensitivity and greater psychological distress. Cluster membership was strongly associated with chronic TMD: 91.5% of TMD cases belonged to the pain-sensitive and global symptoms clusters, whereas 41.2% of controls belonged to the adaptive cluster. Temporomandibular disorder cases in the pain-sensitive and global symptoms clusters also showed greater pain intensity, jaw functional limitation, and more comorbid pain conditions. Similar results were obtained when the same methodology was applied to a smaller case–control study consisting of 199 chronic TMD cases and 201 TMD-free controls. During a median 3-year follow-up period of TMD-free individuals, participants in the global symptoms cluster had greater risk of developing first-onset TMD (hazard ratio = 2.8) compared with participants in the other 2 clusters. Cross-cohort predictive modeling was used to demonstrate the reliability of the clusters. PMID:26928952

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

PubMed

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

2017-09-01

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

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

PubMed

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

2017-01-01

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

The pain drawing as an instrument for identifying cervical spine nerve involvement in chronic whiplash-associated disorders.

PubMed

Bernhoff, Gabriella; Landén Ludvigsson, Maria; Peterson, Gunnel; Bertilson, Bo Christer; Elf, Madeleine; Peolsson, Anneli

2016-01-01

The aim of the study was to investigate the psychometric properties of a standardized assessment of pain drawing with regard to clinical signs of cervical spine nerve root involvement. This cross-sectional study included data collected in a randomized controlled study. Two hundred and sixteen patients with chronic (≥6 months) whiplash-associated disorders, grade 2 or 3, were included in this study. The validity, sensitivity, and specificity of a standardized pain drawing assessment for determining nerve root involvement were analyzed, compared to the clinical assessment. In addition, we analyzed the interrater reliability with 50 pain drawings. Agreement was poor between the standardized pain drawing assessment and the clinical assessment (kappa =0.11, 95% CI: -0.03 to 0.20). Sensitivity was high (93%), but specificity was low (19%). Interrater reliability was good (kappa =0.64, 95% CI: 0.53 to 0.76). The standardized pain drawing assessment of nerve root involvement in chronic whiplash-associated disorders was not in agreement with the clinical assessment. Further research is warranted to optimize the utilization of a pain/discomfort drawing as a supportive instrument for identifying nerve involvement in cervical spinal injuries.

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

PubMed

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

2017-06-01

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

High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation.

PubMed

Vo, L; Drummond, P D

2013-03-01

In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.

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

PubMed

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

2016-08-01

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

Pain modality- and sex-specific effects of COMT genetic functional variants

PubMed Central

Belfer, Inna; Segall, Samantha K.; Lariviere, William R.; Smith, Shad B.; Dai, Feng; Slade, Gary G.; Rashid, Naim U.; Mogil, Jeffrey S.; Campbell, Claudia; Edwards, Robert; Liu, Qian; Bair, Eric; Maixner, William; Diatchenko, Luda

2013-01-01

The enzyme catechol-O-methyltransferase (COMT) metabolizes catecholamine neurotransmitters involved in a number of physiological functions including pain perception. Both human and mouse COMT genes possess functional polymorphisms contributing to inter-individual variability in pain phenotypes such as sensitivity to noxious stimuli, severity of clinical pain and response to pain treatment. In this study, we found that the effects of Comt functional variation in mice are modality-specific. Spontaneous inflammatory nociception and thermal nociception behaviors were correlated the most with the presence of the B2 SINE transposon insertion residing in the 3’UTR mRNA region. Similarly, in humans, COMT functional haplotypes were associated with thermal pain perception and with capsaicin-induced pain. Furthermore, COMT genetic variations contributed to pain behaviors in mice and pain ratings in humans in a sex-specific manner. The ancestral Comt variant, without a B2 SINE insertion, was more strongly associated with sensitivity to capsaicin in female versus male mice. In humans, the haplotype coding for low COMT activity increased capsaicin-induced pain perception in women, but not men. These findings reemphasize the fundamental contribution of COMT to pain processes, and provide a fine-grained resolution of this contribution at the genetic level that can be used to guide future studies in the area of pain genetics. PMID:23701723

Integrative Approach to Pain Genetics Identifies Pain Sensitivity Loci across Diseases

PubMed Central

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

2012-01-01

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

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

PubMed

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

2018-05-01

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

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

Effect of a single session of muscle-biased therapy on pain sensitivity: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Gay, Charles W; Alappattu, Meryl J; Coronado, Rogelio A; Horn, Maggie E; Bishop, Mark D

2013-01-01

Background Muscle-biased therapies (MBT) are commonly used to treat pain, yet several reviews suggest evidence for the clinical effectiveness of these therapies is lacking. Inadequate treatment parameters have been suggested to account for inconsistent effects across studies. Pain sensitivity may serve as an intermediate physiologic endpoint helping to establish optimal MBT treatment parameters. The purpose of this review was to summarize the current literature investigating the short-term effect of a single dose of MBT on pain sensitivity in both healthy and clinical populations, with particular attention to specific MBT parameters of intensity and duration. Methods A systematic search for articles meeting our prespecified criteria was conducted using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, in accordance with guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analysis. Relevant characteristics from studies included type, intensity, and duration of MBT and whether short-term changes in pain sensitivity and clinical pain were noted with MBT application. Study results were pooled using a random-effects model to estimate the overall effect size of a single dose of MBT on pain sensitivity as well as the effect of MBT, dependent on comparison group and population type. Results Reports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups, where 10 groups received active agents, 11 received sham/inert treatments, and eight received no treatment. MBT demonstrated a favorable and consistent ability to modulate pain sensitivity. Short-term modulation of pain sensitivity was associated with short-term beneficial effects on clinical pain. Intensity of MBT, but not duration, was linked with change in pain sensitivity. A meta-analysis was conducted on 17 studies that assessed the effect of MBT on pressure pain thresholds. The results suggest that MBT had a favorable effect on pressure pain thresholds when compared with no-treatment and sham/inert groups, and effects comparable with those of other active treatments. Conclusion The evidence supports the use of pain sensitivity measures by future research to help elucidate optimal therapeutic parameters for MBT as an intermediate physiologic marker. PMID:23403507

Fibromyalgia interacts with age to change the brain☆☆☆

PubMed Central

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

2013-01-01

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

Reliability, validity, sensitivity and specificity of Guajarati version of the Roland-Morris Disability Questionnaire.

PubMed

Nambi, S Gopal

2013-01-01

The most common instruments developed to assess the functional status of patients with Non specific low back pain is the Roland-Morris Disability Questionnaire (RMDQ). Clinical and epidemiological research related to low back pain in the Gujarati population would be facilitated by the availability of well-established outcome measures. To find the reliability, validity, sensitivity and specificity of the Gujarati version of the RMDQ for use in Non Specific Chronic low back pain. A reliability, validity, sensitivity and specificity study of Gujarati version of the Roland-Morris Disability Questionnaire (RMDQ). Thirty out patients with Non Specific Chronic low back pain were assessed by the RMDQ. Reliability is assessed by using internal consistency and the intra-class correlation coefficient (ICC). Internal construct validity is assessed by RASCH Analysis and external construct validity is assessed by association with pain and spinal movement. Clinical calculator was used to determine the sensitivity and specificity. Internal consistency of the RMDQ is found to be adequate (> 0.65) at both times, with high ICC's also at both time points. Internal construct validity of the scale is good, indicating a single underlying construct. Expected associations with pain and spinal movement confirm external construct validity. The Sensitivity and Specificity at cut off point of 0.5 was 80% and 84% with respectively positive predictive value (PPV) of 83.33% and negative predictive value (NPV) of 80.76%. The Questionnaire is at the ordinal level. The RMDQ is a one-dimensional, ordinal measure, which works well in the Gujarati population.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

PubMed Central

Carroll, C. Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469

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

PubMed

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

2013-01-01

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

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.

PubMed

Kosek, Eva; Rosen, Annelie; Carville, Serena; Choy, Ernest; Gracely, Richard H; Marcus, Hanke; Petzke, Frank; Ingvar, Martin; Jensen, Karin B

2017-07-01

Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Regional vs. general anesthesia for total knee and hip replacement: An analysis of postoperative pain perception from the international PAIN OUT registry.

PubMed

Donauer, Katharina; Bomberg, Hagen; Wagenpfeil, Stefan; Volk, Thomas; Meissner, Winfried; Wolf, Alexander

2018-05-14

Total hip and knee replacements are common surgeries, and an optimal pain treatment is essential for early rehabilitation. Since data from randomized controlled trails on the use of regional anesthesia in joint replacements of the lower extremities are conflicting, we analyzed the international PAIN OUT registry for comparison of regional anesthesia vs. general anesthesia regarding pain and morphine consumption on the first postoperative day. International Classification of Diseases-9 (ICD-9) codes were used to identify 2,346 cases for knee and 2,315 for hip arthroplasty between 2010 and 2016 from the PAIN OUT registry. Those were grouped according to anesthesia provided (general, regional, and a combination of both). At the first day after surgery, pain levels and opioid consumption was compared. Adjusted odds ratios (aOR [95% CI]) were calculated with logistic regression and propensity matching was used as a sensitivity analysis. After adjustment for confounders, regional anesthesia was associated with reduced opioid consumption (0.20 [0.13-0.30], p<0.001) and less pain (0.53 [0.36-0.78], p=0.001) than general anesthesia in knee surgery. In hip surgery, regional anesthesia was only associated with reduced opioid consumption (0.17 [0.11-0.26], p<0.001), whereas pain was comparable (1.23 [0.94-1.61], p=0.1). Results from a propensity-matched sensitivity analysis were similar. In total knee arthroplasty, regional anesthesia was associated with less pain and lower opioid consumption. In total hip arthroplasty, regional anesthesia was associated with a lower opioid consumption, however not with reduced pain levels. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

PubMed Central

Brandow, Amanda M.; Wandersee, Nancy J.; Dasgupta, Mahua; Hoffmann, Raymond G.; Hillery, Cheryl A.; Stucky, Cheryl L.; Panepinto, Julie A.

2016-01-01

Summary Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: 1) SCD baseline and controls and 2) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean±standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32.4±11.6 vs. 22.9±7.6, P=0.0009). SP in SCD pain was higher than baseline (78.1±43.4 vs. 32.4±11.6, P=0.004). Haemolysis correlated with increased SP: Hb (r=−0.7, P=0.0002), reticulocyte count (r=0.61, P=0.0016), bilirubin (r=0.68, P=0.0216), LDH (r=0.62, P=0.0332), aspartate aminotransferase (r=0.68, P=0.003). Patients taking hydroxycarbamide had increased SP (β=29.2, P=0.007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment. PMID:27539682

Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia

PubMed Central

Vargas-Alarcón, Gilberto; Fragoso, José-Manuel; Cruz-Robles, David; Vargas, Angélica; Vargas, Alfonso; Lao-Villadóniga, José-Ignacio; García-Fructuoso, Ferrán; Ramos-Kuri, Manuel; Hernández, Fernando; Springall, Rashidi; Bojalil, Rafael; Vallejo, Maite; Martínez-Lavín, Manuel

2007-01-01

Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. Catechol-O-methyltransferase (COMT), an enzyme, is the major catecholamine-clearing pathway. There are several single-nucleotide polymorphisms (SNPs) in the COMT gene associated with the different catecholamine-clearing abilities of the COMT enzyme. These SNPs are in linkage disequilibrium and segregate as 'haplotypes'. Healthy females with a particular COMT gene haplotype (ACCG) producing a defective enzyme are more sensitive to painful stimuli. The objective of our study was to define whether women with FM, from two different countries (Mexico and Spain), have the COMT gene haplotypes that have been previously associated with greater sensitivity to pain. All the individuals in the study were female. Fifty-seven Mexican patients and 78 Spanish patients were compared with their respective healthy control groups. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Six COMT SNPs (rs2097903, rs6269, rs4633, rs4818, rs4680, and rs165599) were genotyped from peripheral blood DNA. In Spanish patients, there was a significant association between three SNPs (rs6269, rs4818, and rs4680) and the presence of FM when compared with healthy controls. Moreover, in Spanish patients with the 'high pain sensitivity' haplotype (ACCG), the disease, as assessed by the FIQ, was more severe. By contrast, Mexican patients displayed only a weak association between rs6269 and rs165599, and some FIQ subscales. In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results. PMID:17961261

Lack of Gender and Age Differences in Pain Measurements Following Exercise in People with Chronic Whiplash-Associated Disorders.

PubMed

Ickmans, Kelly; Malfliet, Anneleen; De Kooning, Margot; Goudman, Lisa; Hubloue, Ives; Schmitz, Tom; Goubert, Dorien; Aguilar-Ferrandiz, Maria Encarnacion

2017-09-01

Individuals with chronic whiplash associated disorders (WAD) present persistent pain in the absence of structural pathology. In these people, altered central pain processing and central sensitization are observed. The role of personal factors, such as gender and age, on pain processing mechanisms in chronic WAD, however, is still unclear. This study investigated possible gender- and age-related differences in self-reported and experimental pain measurements in people with chronic WAD. Besides the exercise-induced response on pain measurements between gender and age subgroups was recorded. Case-control study. University Hospital, Brussels. Self-reported pain and experimental pain measurements (pressure pain thresholds [PPT], occlusion cuff pressure, temporal summation, and conditioned pain modulation) were performed in 52 individuals (26 chronic WAD patients and 26 healthy controls), before and after a submaximal cycle exercise. Lower PPTs and occlusion cuff pressures were shown in chronic WAD in comparison with healthy controls. No gender and age differences regarding PPTs, occlusion cuff pressures and conditioned pain modulation were found in chronic WAD. Within the chronic WAD group, men showed higher self-reported pain compared to women and younger adults showed enhanced generalized pain facilitation compared to older adults. In addition, chronic WAD patients are able to inhibit exercise-induced hyperalgesia, but no gender and age differences in pain response following exercise were found. This study was sufficiently powered to detect differences between the chronic WAD and control group. However, a sufficient power was not reached when patients were divided in age and gender groups. Furthermore, only mechanical stimuli were included in the experimental pain measurements. Besides, psychosocial factors were not taken into account. Some alterations of altered pain processing are present in chronic WAD patients, however not in response to exercise. No gender and age differences in pain measurements were observed in people with chronic WAD.Key words: Neck pain, whiplash associated disorders, chronic pain, personal factors, age, gender, central sensitization, exercise induced hyperalgesia, pressure pain thresholds, self reported pain.

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms.

PubMed

Spierer, Oriel; Felix, Elizabeth R; McClellan, Allison L; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J; Sarantopoulos, Constantine D; Levitt, Roy C; Ehrmann, Klaus; Galor, Anat

2016-02-01

To examine associations between corneal mechanical thresholds and metrics of dry eye. This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = -0.13 to -0.27, P < 0.05 for values between -0.18 and -0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = -0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints.

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms

PubMed Central

Spierer, Oriel; Felix, Elizabeth R.; McClellan, Allison L.; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J.; Sarantopoulos, Constantine D.; Levitt, Roy C.; Ehrmann, Klaus; Galor, Anat

2016-01-01

Purpose To examine associations between corneal mechanical thresholds and metrics of dry eye. Methods This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. Results A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = −0.13 to −0.27, P < 0.05 for values between −0.18 and −0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = −0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Conclusions Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints. PMID:26886896

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

PubMed

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

2013-05-01

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

Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions

PubMed Central

Eller-Smith, Olivia C.; Nicol, Andrea L.; Christianson, Julie A.

2018-01-01

Centralized pain syndromes are associated with changes within the central nervous system that amplify peripheral input and/or generate the perception of pain in the absence of a noxious stimulus. Examples of idiopathic functional disorders that are often categorized as centralized pain syndromes include fibromyalgia, chronic pelvic pain syndromes, migraine, and temporomandibular disorder. Patients often suffer from widespread pain, associated with more than one specific syndrome, and report fatigue, mood and sleep disturbances, and poor quality of life. The high degree of symptom comorbidity and a lack of definitive underlying etiology make these syndromes notoriously difficult to treat. The main purpose of this review article is to discuss potential mechanisms of centrally-driven pain amplification and how they may contribute to increased comorbidity, poorer pain outcomes, and decreased quality of life in patients diagnosed with centralized pain syndromes, as well as discuss emerging non-pharmacological therapies that improve symptomology associated with these syndromes. Abnormal regulation and output of the hypothalamic-pituitary-adrenal (HPA) axis is commonly associated with centralized pain disorders. The HPA axis is the primary stress response system and its activation results in downstream production of cortisol and a dampening of the immune response. Patients with centralized pain syndromes often present with hyper- or hypocortisolism and evidence of altered downstream signaling from the HPA axis including increased Mast cell (MC) infiltration and activation, which can lead to sensitization of nearby nociceptive afferents. Increased peripheral input via nociceptor activation can lead to “hyperalgesic priming” and/or “wind-up” and eventually to central sensitization through long term potentiation in the central nervous system. Other evidence of central modifications has been observed through brain imaging studies of functional connectivity and magnetic resonance spectroscopy and are shown to contribute to the widespreadness of pain and poor mood in patients with fibromyalgia and chronic urological pain. Non-pharmacological therapeutics, including exercise and cognitive behavioral therapy (CBT), have shown great promise in treating symptoms of centralized pain. PMID:29487504

When sex hurts, anxiety and fear orient attention towards pain.

PubMed

Payne, Kimberley A; Binik, Yitzchak M; Amsel, Rhonda; Khalifé, Samir

2005-08-01

Hypervigilance for pain-relevant stimuli has been associated with anxiety, fear of pain and anxiety sensitivity. This attentional bias has been primarily investigated in heterogeneous pain groups or pain-free controls, but has not been examined in pain conditions where anxiety and fear are likely to play a central role. Due to the intimate and interpersonal nature of genital pain experienced during sexual intercourse, Vulvar Vestibulitis Syndrome (VVS) constitutes an ideal sample in which to investigate the role of cognitive and affective factors in pain perception and maintenance. Seventeen women suffering from VVS and an equal number of age and education matched control women completed an emotional Stroop and memory recall task in addition to a series of questionnaires assessing pain-hypervigilance, state and trait anxiety, fear of pain, and anxiety sensitivity. VVS sufferers reported hypervigilance for coital pain and also exhibited a selective attentional bias towards pain stimuli on the emotional Stroop task as compared with controls. This effect was predicted by state and trait anxiety and fear of pain. According to these data, treament strategies for VVS should target anxiety and fear in addition to sensory systems.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

PubMed

Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-07-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

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.

Identification of neuropathic pain in patients with neck/upper limb pain: application of a grading system and screening tools.

PubMed

Tampin, Brigitte; Briffa, Noelle Kathryn; Goucke, Roger; Slater, Helen

2013-12-01

The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain has proposed a grading system for the presence of neuropathic pain (NeP) using the following categories: no NeP, possible, probable, or definite NeP. To further evaluate this system, we investigated patients with neck/upper limb pain with a suspected nerve lesion, to explore: (i) the clinical application of this grading system; (ii) the suitability of 2 NeP questionnaires (Leeds Assessment of Neuropathic Symptoms and Signs pain scale [LANSS] and the painDETECT questionnaire [PD-Q]) in identifying NeP in this patient cohort; and (iii) the level of agreement in identifying NeP between the NeuPSIG classification system and 2 NeP questionnaires. Patients (n = 152; age 52 ± 12 years; 53% male) completed the PD-Q and LANSS questionnaire and underwent a comprehensive clinical examination. The NeuPSIG grading system proved feasible for application in this patient cohort, although it required considerable time and expertise. Both questionnaires failed to identify a large number of patients with clinically classified definite NeP (LANSS sensitivity 22%, specificity 88%; PD-Q sensitivity 64%, specificity 62%). These lowered sensitivity scores contrast with those from the original PD-Q and LANSS validation studies and may reflect differences in the clinical characteristics of the study populations. The diagnostic accuracy of LANSS and PD-Q for the identification of NeP in patients with neck/upper limb pain appears limited. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The association of greater dispositional optimism with less endogenous pain facilitation is indirectly transmitted through lower levels of pain catastrophizing

PubMed Central

Goodin, Burel R.; Glover, Toni L.; Sotolongo, Adriana; King, Christopher D.; Sibille, Kimberly T.; Herbert, Matthew S.; Cruz-Almeida, Yenisel; Sanden, Shelley H.; Staud, Roland; Redden, David T.; Bradley, Laurence A.; Fillingim, Roger B.

2012-01-01

Dispositional optimism has been shown to beneficially influence various experimental and clinical pain experiences. One possibility that may account for decreased pain sensitivity among individuals who report greater dispositional optimism is less use of maladaptive coping strategies like pain catastrophizing, a negative cognitive/affective response to pain. An association between dispositional optimism and conditioned pain modulation (CPM), a measure of endogenous pain inhibition, has previously been reported. However, it remains to be determined whether dispositional optimism is also associated with temporal summation (TS), a measure of endogenous pain facilitation. The current study examined whether pain catastrophizing mediated the association between dispositional optimism and TS among 140 older, community-dwelling adults with symptomatic knee osteoarthritis. Individuals completed measures of dispositional optimism and pain catastrophizing. TS was then assessed using a tailored heat pain stimulus on the forearm. Greater dispositional optimism was significantly related to lower levels of pain catastrophizing and TS. Bootstrapped confidence intervals revealed that less pain catastrophizing was a significant mediator of the relation between greater dispositional optimism and diminished TS. These findings support the primary role of personality characteristics such as dispositional optimism in the modulation of pain outcomes by abatement of endogenous pain facilitation and less use of catastrophizing. PMID:23218934

Pavlovian second-order conditioned analgesia.

PubMed

Ross, R T

1986-01-01

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

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

PubMed

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

2014-05-01

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

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

PubMed

Nakajima, Motohiro; Al'Absi, Mustafa

2014-10-01

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

Impaired conditioned pain modulation in youth with functional abdominal pain

PubMed Central

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

2016-01-01

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

Impaired conditioned pain modulation in youth with functional abdominal pain.

PubMed

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

2016-10-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed Central

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

2017-01-01

Body image represents a multidimensional concept including body image evaluation and perception of body appearance. Disturbances of body image perception are considered to be one of the central aspects of anorexia nervosa and bulimia nervosa. There is growing evidence that body image distortion can be associated with changes in pain perception. The aim of our study was to examine the associations between body image perception, body dissatisfaction, and nociception in women with eating disorders and age-matched healthy control women. We measured body dissatisfaction and pain sensitivity in 61 patients with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnoses of eating disorders (31 anorexia nervosa and 30 bulimia nervosa) and in 30 healthy women. Thermal pain threshold latencies were evaluated using an analgesia meter and body image perception and body dissatisfaction were assessed using Anamorphic Micro software (digital pictures of their own body distorted into larger-body and thinner-body images). Patients with eating disorders overestimated their body size in comparison with healthy controls, but the two groups did not differ in body dissatisfaction. In anorexia and bulimia patient groups, body dissatisfaction (calculated in pixels as desired size/true image size) correlated with pain threshold latencies (r=0.55, p=0.001), while between body image perception (determined as estimation size/true image size) and pain threshold, no correlation was found. Thus, we demonstrated that in patients with eating disorders, pain perception is significantly associated with emotional contrary to sensory (visual) processing of one’s own body image. The more the patients desired to be thin, the more pain-sensitive they were. Our findings based on some shared mechanisms of body dissatisfaction and pain perception support the significance of negative emotions specific for eating disorders and contribute to better understanding of the psychosomatic characteristics of this spectrum of illnesses. PMID:28761371

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

PubMed

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

2017-10-01

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

A clinical perspective on a pain neuroscience education approach to manual therapy.

PubMed

Louw, Adriaan; Nijs, Jo; Puentedura, Emilio J

2017-07-01

In recent years, there has been an increased interest in pain neuroscience education (PNE) in physical therapy. There is growing evidence for the efficacy of PNE to decrease pain, disability, fear-avoidance, pain catastrophization, limited movement, and health care utilization in people struggling with pain. PNE teaches people in pain more about the biology and physiology of their pain experience including processes such as central sensitization, peripheral sensitization, allodynia, inhibition, facilitation, neuroplasticity and more. PNE's neurobiological model often finds itself at odds with traditional biomedical models used in physical therapy. Traditional biomedical models, focusing on anatomy, pathoanatomy, and biomechanics have been shown to have limited efficacy in helping people understand their pain, especially chronic pain, and may in fact even increase a person's pain experience by increasing fear-avoidance and pain catastrophization. An area of physical therapy where the biomedical model is used a lot is manual therapy. This contrast between PNE and manual therapy has seemingly polarized followers from each approach to see PNE as a 'hands-off' approach even having clinicians categorize patients as either in need of receiving PNE (with no hands-on), or hands-on with no PNE. In this paper, we explore the notion of PNE and manual therapy co-existing. PNE research has shown to have immediate effects of various clinical signs and symptoms associated with central sensitization. Using a model of sensitization (innocuous, noxious, and allodynia), we argue that PNE can be used in a manual therapy model, especially treating someone where the nervous system has become increasingly hypervigilant. Level of Evidence : VII.

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

PubMed Central

Bialosky, Joel E.; Robinson, Michael E.

2014-01-01

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

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

PubMed

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

2017-07-01

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

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

PubMed

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

2015-07-01

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

Ethnic differences in physical pain sensitivity: role of acculturation.

PubMed

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

2013-01-01

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

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

PubMed

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

2014-12-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-02-01

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

Sex-dependent effects of cannabis-induced analgesia.

PubMed

Cooper, Ziva D; Haney, Margaret

2016-10-01

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

Sex-Dependent Effects Of Cannabis-Induced Analgesia

PubMed Central

Cooper, Ziva D.; Haney, Margaret

2016-01-01

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

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

PubMed

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

2017-08-02

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

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

PubMed

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

2017-02-01

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

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

PubMed

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

2014-10-01

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

Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: etiological contribution to complex regional pain syndromes (Part II).

PubMed

Wang, Fuzhou; Stefano, George B; Kream, Richard M

2014-07-12

Cumulating evidence indicated that nerve injury-associated cellular and molecular changes play an essential role in contributing to the development of pathological pain, and more recent findings implicated the critical role of epigenetic mechanisms in pain-related sensitization in the DRG subsequent to nerve injury. In this part of the dyad review (Part II), we reviewed and paid special attention on the etiological contribution of DGR gene expression modulated by epigenetic mechanisms of CRPS. As essential effectors to different molecular activation, we first discussed the activation of various signaling pathways that subsequently from nerve injury, and in further illustrated the fundamental and functional underpinnings of nerve injury-induced pain, in which we argued for the potential epigenetic mechanisms in response to sensitizing stimuli or injury. Therefore, understanding the specific mediating factors that influence individual epigenetic differences contributing to pain sensitivity and responsiveness to analgesics possesses crucial clinical implications.

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

PubMed

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

2017-08-30

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

Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-07-01

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

Association of Leptin with Body Pain in Women

PubMed Central

Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D.; Stefanick, Marcia L.

2016-01-01

Abstract Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia. PMID:27028709

Association of Leptin with Body Pain in Women.

PubMed

Younger, Jarred; Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D; Stefanick, Marcia L

2016-07-01

Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

PubMed Central

Galor, A; Levitt, R C; Felix, E R; Martin, E R; Sarantopoulos, C D

2015-01-01

Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain. PMID:25376119

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

PubMed Central

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

2018-01-01

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

Painful neurotrophins and their role in visceral pain.

PubMed

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

2018-04-01

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

Postoperative Pain and Analgesia: Is There a Genetic Basis to the Opioid Crisis?

PubMed

Elmallah, Randa K; Ramkumar, Prem N; Khlopas, Anton; Ramkumar, Rathika R; Chughtai, Morad; Sodhi, Nipun; Sultan, Assem A; Mont, Michael A

2018-06-01

Multiple factors have been implicated in determining why certain patients have increased postoperative pain, with the potential to develop chronic pain. The purpose of this study was to: 1) identify and describe genes that affect postoperative pain perception and control; 2) address modifiable risk factors that result in epigenetic altered responses to pain; and 3) characterize differences in pain sensitivity and thresholds between opioid-naïve and opioid-dependent patients. Three electronic databases were used to conduct the literature search: Pubmed, EBSCO host, and SCOPUS. A total of 372 abstracts were reviewed, of which 46 studies were deemed relevant and are included in this review. Specific gene alterations that were shown to affect postoperative pain control included single nucleotide polymorphisms in the mu, kappa, and delta opioid receptors, ion channel genes, cytotoxic T-cells, glutamate receptors and cytokine genes, among others. Alcoholism, obesity, and smoking were all linked with genetic polymorphisms that altered pain sensitivity. Opioid abuse was found to be associated with a poorer response to analgesics postoperatively, as well as a risk for prescription overdose. Although pain perception has multiple complex influences, the greatest variability seen in response to opioids among postoperative patients known to date can be traced to genetic differences in opioid metabolism. Further study is needed to determine the clinical significance of these genetic associations.

Contextual modulation of pain sensitivity utilising virtual environments

PubMed Central

Smith, Ashley; Carlow, Klancy; Biddulph, Tara; Murray, Brooke; Paton, Melissa; Harvie, Daniel S

2017-01-01

Background: Investigating psychological mechanisms that modulate pain, such as those that might be accessed by manipulation of context, is of great interest to researchers seeking to better understand and treat pain. The aim of this study was to better understand the interaction between pain sensitivity, and contexts with inherent emotional and social salience – by exploiting modern immersive virtual reality (VR) technology. Methods: A within-subjects, randomised, double-blinded, repeated measures (RM) design was used. In total, 25 healthy participants were exposed to neutral, pleasant, threatening, socially positive and socially negative contexts, using an Oculus Rift DK2. Pressure pain thresholds (PPTs) were recorded in each context, as well as prior to and following the procedure. We also investigated whether trait anxiety and pain catastrophisation interacted with the relationship between the different contexts and pain. Results: Pressure pain sensitivity was not modulated by context (p = 0.48). Anxiety and pain catastrophisation were not significantly associated with PPTs, nor did they interact with the relationship between context and PPTs. Conclusion: Contrary to our hypothesis, socially and emotionally salient contexts did not influence pain thresholds. In light of other research, we suggest that pain outcomes might only be tenable to manipulation by contextual cues if they specifically manipulate the meaning of the pain-eliciting stimulus, rather than manipulate psychological state generally – as per the current study. Future research might exploit immersive VR technology to better explore the link between noxious stimuli and contexts that directly alter its threat value. PMID:28491299

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

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

PubMed

Defrin, Ruth; Devor, Marshall; Brill, Silviu

2014-12-01

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

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.

[Psychosocial stressors and pain sensitivity in chronic pain disorder with somatic and psychological factors (F45.41)].

PubMed

Studer, M; Stewart, J; Egloff, N; Zürcher, E; von Känel, R; Brodbeck, J; Grosse Holtforth, M

2017-02-01

Increased pain sensitivity is characteristic for patients with chronic pain disorder with somatic and psychological factors (F45.41). Persistent stress can induce, sustain, and intensify pain sensitivity, thereby modulating pain perception. In this context, it would be favorable to investigate which psychosocial stressors are empirically linked to pain sensitivity. The aim of this study was to examine the relationship between psychosocial stressors and pain sensitivity in a naturalistic sample of patients with chronic pain disorder with somatic and psychological factors (F45.41). We assessed 166 patients with chronic pain disorder with somatic and psychological factors (F45.41) at entry into an inpatient pain clinic. Pain sensitivity was measured with a pain provocation test (Algopeg) at the middle finger and earlobe. Stressors assessed were exposure to war experiences, adverse childhood experiences, illness-related inability to work, relationship problems, and potentially life-threatening accidents. Correlation analyses and structural equation modeling were used to examine which stressors showed the strongest prediction of pain sensitivity. Patients exhibited generally heightened pain sensitivity. Both exposure to war and illness-related inability to work showed significant bivariate correlations with pain sensitivity. In addition to age, they also predicted a further increase in pain sensitivity in the structural equation model. Bearing in mind the limitations of this cross-sectional study, these findings may contribute to a better understanding of the link between psychosocial stressors and pain sensitivity.

Quality pain management outcomes: the power of place.

PubMed

Wild, L R; Mitchell, P H

2000-01-01

This study explores how an organization, as the context of care, influences nursing practice and a nursing-sensitive, quality health outcome-pain management. The results provide important insights into organizational patterns associated with favorable pain management-related outcomes as well as the congruence between and among subunits within the organization. Outcomes were most favorable on units where nurses had attitudes supportive of aggressive pain management and higher levels of coordination and discretion.

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

PubMed

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

2017-08-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2013-01-01

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

Association between Genetic Polymorphisms in Cav2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery

PubMed Central

Fukuda, Ken-ichi; Kasai, Shinya; Hasegawa, Junko; Hayashida, Masakazu; Minami, Masabumi; Ikeda, Kazutaka

2013-01-01

Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca2+ channels (VACCs) play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Cav2.3 (R-type) VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide polymorphisms (SNPs) of the human CACNA1E (calcium channel, voltage-dependent, R type, alpha 1E subunit) gene that encodes Cav2.3 VACCs influence the analgesic effects of opioids. Thus, the present study examined associations between fentanyl sensitivity and SNPs in the human CACNA1E gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. We first conducted linkage disequilibrium (LD) analyses of 223 SNPs in a region that contains the CACNA1E gene using genomic samples from 100 patients, and a total of 13 LD blocks with 42 Tag SNPs were observed within and around the CACNA1E gene region. In the preliminary study using the same 100 genomic samples, only the rs3845446 A/G SNP was significantly associated with perioperative fentanyl use among these 42 Tag SNPs. In a confirmatory study using the other 255 genomic samples, this SNP was also significantly associated with perioperative fentanyl use. Thus, we further analyzed associations between genotypes of this SNP and all of the clinical data using a total of 355 samples. The rs3845446 A/G SNP was associated with intraoperative fentanyl use, 24 h postoperative fentanyl requirements, and perioperative fentanyl use. Subjects who carried the minor G allele required significantly less fentanyl for pain control compared with subjects who did not carry this allele. Although further validation is needed, the present findings show the possibility of the involvement of CACNA1E gene polymorphisms in fentanyl sensitivity. PMID:23940630

Chronic Pain Without Clear Etiology in Low- and Middle-Income Countries: A Narrative Review.

PubMed

Jackson, Tracy; Thomas, Sarah; Stabile, Victoria; Han, Xue; Shotwell, Matthew; McQueen, K A Kelly

2016-06-01

Globally, 8 of the top 12 disabling conditions are related either to chronic pain or to the psychological conditions strongly associated with persistent pain. In this narrative review, we explore the demographic and psychosocial associations with chronic pain exclusively from low- and middle-income countries (LMICs) and compare them with current global data. One hundred nineteen publications in 28 LMICs were identified for review; associations with depression, anxiety, posttraumatic stress, insomnia, disability, gender, age, rural/urban location, education level, income, and additional sites of pain were analyzed for each type of chronic pain without clear etiology. Of the 119 publications reviewed, pain was described in association with disability in 50 publications, female gender in 40 publications, older age in 34 publications, depression in 36 publications, anxiety in 19 publications, and multiple somatic complaints in 13 publications. Women, elderly patients, and workers, especially in low-income and low-education subgroups, were more likely to have pain in multiple sites, mood disorders, and disabilities. In high-income countries, multisite pain without etiology, female gender, and association with mood disturbance and disability may be suggestive of a central sensitization syndrome (CSS). Because each type of prevalent chronic pain without known etiology reviewed had similar associations in LMICs, strategies for assessment and treatment of chronic pain worldwide should consider the possibility of prevalent CSS. Recognition is especially critical in resource-poor areas, because treatment of CSS is vastly different than localized chronic pain.

Gender role affects experimental pain responses: a systematic review with meta-analysis.

PubMed

Alabas, O A; Tashani, O A; Tabasam, G; Johnson, M I

2012-10-01

Gender role refers to the culturally and socially constructed meanings that describe how women and men should behave in certain situations according to feminine and masculine roles learned throughout life. The aim of this meta-analysis was to evaluate the relationship between gender role and experimental pain responses in healthy human participants. We searched computerized databases for studies published between January 1950 and May 2011 that had measured gender role in healthy human adults and pain response to noxious stimuli. Studies were entered into a meta-analysis if they calculated a correlation coefficient (r) for gender role and experimental pain. Searches yielded 4465 'hits' and 13 studies were eligible for review. Sample sizes were 67-235 participants and the proportion of female participants was 45-67%. Eight types of gender role instrument were used. Meta-analysis of six studies (406 men and 539 women) found a significant positive correlation between masculine and feminine personality traits and pain threshold and tolerance, with a small effect size (r = 0.17, p = 0.01). Meta-analysis of four studies (263 men and 297 women) found a significant negative correlation between gender stereotypes specific to pain and pain threshold and tolerance, with a moderate effect size (r = -0.41, p < 0.001). In conclusion, individuals who considered themselves more masculine and less sensitive to pain than the typical man showed higher pain thresholds and tolerances. Gender stereotypes specific to pain scales showed stronger associations with sex differences in pain sensitivity response than masculine and feminine personality trait scales. © 2012 European Federation of International Association for the Study of Pain Chapters.

Neural and psychosocial mechanisms of pain sensitivity in fibromyalgia.

PubMed

English, Brian

2014-06-01

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

Ecological aspects of pain in sensory modulation disorder.

PubMed

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

2015-01-01

Sensory Modulation Disorder (SMD) interferes with the daily life participation of otherwise healthy individuals and is characterized by over-, under- or seeking responsiveness to naturally occurring sensory stimuli. Previous laboratory findings indicate pain hyper-sensitivity in SMD individuals suggesting CNS alteration in pain processing and modulation. However, laboratory studies lack ecological validity, and warrant clinical completion in order to elicit a sound understanding of the phenomenon studied. Thus, this study explored the association between sensory modulation and pain in a daily life context in a general population sample. Daily life context of pain and sensations were measured in 250 adults (aged 23-40 years; 49.6% males) using 4 self-report questionnaires: Pain Sensitivity Questionnaire (PSQ) and Pain Catastrophizing Scale (PCS) to evaluate the sensory and cognitive aspects of pain; the Sensory Responsiveness Questionnaire (SRQ) to appraise SMD; and the Short Form - 36 Health Survey, version 2 (SF36) to assess health related Quality of Life (QoL). Thirty two individuals (12.8%) were found with over-responsiveness type of SMD, forming the SOR-SMD group. While no group differences (SOR-SMD vs. Non-SMD) were found, low-to-moderate total sample correlations were demonstrated between the SRQ-Aversive sub-scale and i) PSQ total (r=0.31, p<0.01) and sub-scales scores (r=0.27-0.28, p<0.01), as well as ii) PCS total and the sub-scales of Rumination and Helplessness scores (r=0.15, p<0.05). PSQ total and sub-scale scores were more highly correlated with SRQ-Aversive in the SOR-SMD group (r=0.57-0.68, p=0.03-<0.01) compared to Non-SMD group. The Physical Health - Total score (but not the Mental Health - Total) of the SF36 was lower for the SOR-SMD group (p=0.03), mainly due to the difference in the Body pain sub-scale (p=0.04). Results suggest that SOR-SMD is strongly associated with the sensory aspect of pain but weakly associated with the cognitive aspect. This indicates that SMD co-occurs with daily pain sensitivity, thus reducing QoL, but less with the cognitive-catastrophizing manifestation of pain perception. Copyright © 2015 Elsevier Ltd. All rights reserved.

Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: etiological contribution to complex regional pain syndromes (Part I).

PubMed

Wang, Fuzhou; Stefano, George B; Kream, Richard M

2014-06-25

DRG is of importance in relaying painful stimulation to the higher pain centers and therefore could be a crucial target for early intervention aimed at suppressing primary afferent stimulation. Complex regional pain syndrome (CRPS) is a common pain condition with an unknown etiology. Recently added new information enriches our understanding of CRPS pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, and mechanisms of pain modulation, central sensitization, and autonomic functions in CRPS revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of CRPS. Epigenetics refers to mitotically and meiotically heritable changes in gene expression that do not affect the DNA sequence. As epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, neurotransmitter responsiveness, and analgesic sensitivity, they are likely key factors in the development of chronic pain. In this dyad review series, we systematically examine the nerve injury-related changes in the neurological system and their contribution to CRPS. In this part, we first reviewed and summarized the role of neural sensitization in DRG neurons in performing function in the context of pain processing. Particular emphasis is placed on the cellular and molecular changes after nerve injury as well as different models of inflammatory and neuropathic pain. These were considered as the potential molecular bases that underlie nerve injury-associated pathogenesis of CRPS.

Towards a mechanism-based approach to pain management in osteoarthritis

PubMed Central

Malfait, Anne-Marie; Schnitzer, Thomas J.

2014-01-01

Pain is the defining symptom of osteoarthritis (OA), yet available treatment options, of which NSAIDs are the most common, provide inadequate pain relief and are associated with serious health risks when used long term. Chronic pain pathways are subject to complex levels of control and modulation, both in the periphery and in the central nervous system. Ongoing clinical and basic research is uncovering how these pathways operate in OA. Indeed, clinical investigation into the types of pain associated with progressive OA, the presence of central sensitization, the correlation with structural changes in the joint, and the efficacy of novel analgesics affords new insights into the pathophysiology of OA pain. Moreover, studies in disease-specific animal models enable the unravelling of the cellular and molecular pathways involved. We expect that increased understanding of the mechanisms by which chronic OA-associated pain is generated and maintained will offer opportunities for targeting and improving the safety of analgesia. In addition, using clinical and genetic approaches, it might become possible to identify subsets of patients with pain of different pathophysiology, thus enabling a tailored approach to pain management. PMID:24045707

Genetic Contributions to Clinical Pain and Analgesia: Avoiding Pitfalls in Genetic Research

PubMed Central

Kim, Hyungsuk; Clark, David; Dionne, Raymond A.

2010-01-01

Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment. Perspective We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain. Based on this evidence and the experience of false associations that have occurred in other related disciplines, we provide recommendations for avoiding pitfalls in pain genetic research. PMID:19559388

TRPs in Pain Sensation

PubMed Central

Jardín, Isaac; López, José J.; Diez, Raquel; Sánchez-Collado, José; Cantonero, Carlos; Albarrán, Letizia; Woodard, Geoffrey E.; Redondo, Pedro C.; Salido, Ginés M.; Smani, Tarik; Rosado, Juan A.

2017-01-01

According to the International Association for the Study of Pain (IASP) pain is characterized as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage”. The TRP super-family, compressing up to 28 isoforms in mammals, mediates a myriad of physiological and pathophysiological processes, pain among them. TRP channel might be constituted by similar or different TRP subunits, which will result in the formation of homomeric or heteromeric channels with distinct properties and functions. In this review we will discuss about the function of TRPs in pain, focusing on TRP channles that participate in the transduction of noxious sensation, especially TRPV1 and TRPA1, their expression in nociceptors and their sensitivity to a large number of physical and chemical stimuli. PMID:28649203

Emotion-focused coping and distraction: sex differences in the influence of anxiety sensitivity during noxious heat stimulation.

PubMed

Thompson, T; Keogh, E; Chen, M J-L; French, C C

2012-03-01

While previous research has indicated that the relative efficacy of attentional strategies on pain may be influenced by anxiety sensitivity (AS) and sex, no study appears to have examined this within the context of an emotion-focus versus distraction paradigm. The present study compared the effect of attentional emotion-focus and distraction instructions on pain response with noxious heat stimulation in 114 healthy adults (62 women and 52 men) varying in levels of AS. Results indicated that men reported a significantly higher mean tolerance time than women. Moderated regression analysis also revealed a significant strategy × anxiety sensitivity × sex interaction on pain tolerance. For those low in AS, relative efficacy was dependent upon sex, with distraction superior to emotion-focusing in women, but with strategies equivalent in men. For those high in AS, however, distraction resulted in uniformly greater pain tolerance than attentional emotion-focusing. These results indicate that AS and sex may be influential in determining the relative effectiveness of distraction and emotion-based attentional strategies for pain management. © 2011 European Federation of International Association for the Study of Pain Chapters.

Impact of chronobiology on neuropathic pain treatment.

PubMed

Gilron, Ian

2016-01-01

Inflammatory pain exhibits circadian rhythmicity. Recently, a distinct diurnal pattern has been described for peripheral neuropathic conditions. This diurnal variation has several implications: advancing understanding of chronobiology may facilitate identification of new and improved treatments; developing pain-contingent strategies that maximize treatment at times of the day associated with highest pain intensity may provide optimal pain relief as well as minimize treatment-related adverse effects (e.g., daytime cognitive dysfunction); and consideration of the impact of chronobiology on pain measurement may lead to improvements in analgesic study design that will maximize assay sensitivity of clinical trials. Recent and ongoing chronobiology studies are thus expected to advance knowledge and treatment of neuropathic pain.

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.

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

PubMed

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

2015-09-01

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

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

PubMed Central

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

2007-01-01

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

Can axial pain be helpful to determine surgical level in the multilevel cervical radiculopathy?

PubMed

Suh, Bo-Kyung; You, Ki Han; Park, Moon Soo

2017-01-01

Spine surgeons are required to differentiate symptomatic cervical disc herniation with asymptomatic radiographic herniation. Although the dermatomal sensory dysfunction of upper extremity is the most important clue, axial pain including cervicogenic headache and parascapular pain may be helpful to find surgical target level. However, there is no review article about the axial pain originated from cervical spondylotic radiculopathy and relieved by surgical decompression. The purpose is to review the literatures about the axial pain, which can be utilized in determining target level to be decompressed in the patients with cervical radiculopathy at multiple levels. Cervicogenic headaches of suboccipital headaches, retro-orbital pain, retro-auricular pain, or temporal pain may be associated with C2, C3, and C4 radiculopathies. The pain around scapula may be associated with C5, C6, C7, and C8 radiculopathies. However, there is insufficient evidence to make recommendations for the use in clinical practice because they did not evaluate sensitivity and specificity.

Implantation of hyaluronic acid hydrogel prevents the pain phenotype in a rat model of intervertebral disc injury

PubMed Central

Sakai, Daisuke; Dockery, Peter

2018-01-01

Painful intervertebral disc degeneration is mediated by inflammation that modulates glycosylation and induces hyperinnervation and sensory sensitization, which result in discogenic pain. Hyaluronic acid (HA) used as a therapeutic biomaterial can reduce inflammation and pain, but the effects of HA therapy on glycosylation and pain associated with disc degeneration have not been previously determined. We describe a novel rat model of pain induced by intervertebral disc injury, with validation of the pain phenotype by morphine treatment. Using this model, we assessed the efficacy of HA hydrogel for the alleviation of pain, demonstrating that it reduced nociceptive behavior, an effect associated with down-regulation of nociception markers and inhibition of hyperinnervation. Furthermore, HA hydrogel altered glycosylation and modulated key inflammatory and regulatory signaling pathways, resulting in attenuation of inflammation and regulation of matrix components. Our results suggest that HA hydrogel is a promising clinical candidate for the treatment of back pain caused by degenerated discs. PMID:29632893

Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses.

PubMed

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

2015-10-01

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

Pain and suicidality: Insights from reward and addiction neuroscience

PubMed Central

Elman, Igor; Borsook, David; Volkow, Nora D.

2016-01-01

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system’s role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain-and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other “reward deficiency syndromes” and a new proposal for “enhanced anti-reward syndromes”. We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. PMID:23827972

Pain and suicidality: insights from reward and addiction neuroscience.

PubMed

Elman, Igor; Borsook, David; Volkow, Nora D

2013-10-01

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain- and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other "reward deficiency syndromes" and a new proposal for "enhanced anti-reward syndromes". We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. Published by Elsevier Ltd.

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

PubMed

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

2017-08-01

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

New concepts on functional chronic pelvic and perineal pain: pathophysiology and multidisciplinary management.

PubMed

Ploteau, Stéphane; Labat, Jean Jacques; Riant, Thibault; Levesque, Amélie; Robert, Roger; Nizard, Julien

2015-03-01

The management of chronic pelvic and perineal pain has been improved by a better understanding of the mechanisms of this pain and an optimized integrated multidisciplinary approach to the patient. The concept of organic lesions responsible for a persistent nociceptive factor has gradually been replaced by that of dysregulation of nociceptive messages derived from the pelvis and perineum. In this setting, painful diseases identified by organ specialists are usually also involved and share several common denominators (triggering factors, predisposing clinical context). These diseases include painful bladder syndrome, irritable bowel syndrome, vulvodynia, and chronic pelvic pain syndrome. The painful symptoms vary from one individual to another and according to his or her capacity to activate pain inhibition/control processes. Although the patient often attributes chronic pain to a particular organ (with the corollary that pain will persist until the organ has been treated), this pain is generally no longer derived from the organ but is expressed via this organ. Several types of clinical presentation of complex pelvic pain have therefore been pragmatically identified to facilitate the management of treatment failures resulting from a purely organ-based approach, which can also reinforce the patient's impression of incurability. These subtypes correspond to neuropathic pain, central sensitization (fibromyalgia), complex regional pain syndrome, and emotional components similar to those observed in post-traumatic stress disorder. These various components are also often associated and self-perpetuating. Consequently, when pelvic pain cannot be explained by an organ disease, this model, using each of these four components associated with their specific mechanisms, can be used to propose personalized treatment options and also to identify patients at high risk of postoperative pelvic pain (multi-operated patients, central sensitization, post-traumatic stress disorder, etc.), which constitutes a major challenge for prevention of these types of pain that have major implications for patients and society.

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

PubMed

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

2018-04-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2018-03-01

Mounting evidence indicates that stress influences the experience of pain. Exposure to psychosocial stress disrupts bi-directional communication pathways between the central nervous system and peripheral immune system, and can exacerbate the frequency and severity of pain experienced by stressed subjects. Repeated social defeat (RSD) is a murine model of psychosocial stress that recapitulates the immune and behavioral responses to stress observed in humans, including activation of stress-reactive neurocircuitry and increased pro-inflammatory cytokine production. It is unclear, however, how these stress-induced neuroimmune responses contribute to increased pain sensitivity in mice exposed to RSD. Here we used a technique of regional analgesia with local anesthetics in mice to block the development of mechanical allodynia during RSD. We next investigated the degree to which pain blockade altered stress-induced neuroimmune activation and depressive-like behavior. Following development of a mouse model of regional analgesia with discrete sensory blockade over the dorsal-caudal aspect of the spine, C57BL/6 mice were divided into experimental groups and treated with Ropivacaine (0.08%), Liposomal Bupivacaine (0.08%), or Vehicle (0.9% NaCl) prior to exposure to stress. This specific region was selected for analgesia because it is the most frequent location for aggression-associated pain due to biting during RSD. Mechanical allodynia was assessed 12 h after the first, third, and sixth day of RSD after resolution of the sensory blockade. In a separate experiment, social avoidance behavior was determined after the sixth day of RSD. Blood, bone marrow, brain, and spinal cord were collected for immunological analyses after the last day of RSD in both experiments following behavioral assessments. RSD increased mechanical allodynia in an exposure-dependent manner that persisted for at least one week following cessation of the stressor. Mice treated with either Ropivacaine or Liposomal Bupivacaine did not develop mechanical allodynia following exposure to stress, but did develop social avoidance behavior. Neither drug affected stress-induced activation of monocytes in the bone marrow, blood, or brain. Neuroinflammatory responses developed in all treatment groups, as evidenced by elevated IL-1β mRNA levels in the brain and spinal cord after RSD. In this study, psychosocial stress was associated with increased pain sensitivity in mice. Development of mechanical allodynia with RSD was blocked by regional analgesia with local anesthetics, Ropivacaine or Liposomal Bupivacaine. Despite blocking mechanical allodynia, these anesthetic interventions did not prevent neuroimmune activation or social avoidance associated with RSD. These data suggest that stress-induced neuroinflammatory changes are not associated with increased sensitivity to pain following RSD. Thus, blocking peripheral nociception was effective in inhibiting enhanced pain signaling without altering stress-induced immune or behavioral responses. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered pain sensitivity and axioscapular muscle activity in neck pain patients compared with healthy controls.

PubMed

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

2017-11-01

Previous studies have indicated that neck pain patients feel increased symptoms following upper limb activities, and altered axioscapular muscle function has been proposed as a contributing factor. Pain sensitivity and muscle activity, during arm movements, were assessed in neck pain patients and controls. Patients with ongoing insidious-onset neck pain (IONP, N = 16) and whiplash-associated disorders (WAD, N = 9) were included along with sex- and age-matched controls (N = 25). Six series of repeated arm abductions were performed during electromyographic (EMG) recordings from eight bilateral muscles. The first and last three series were separated by 8 min and 42 s, respectively. Each series consisted of three slow and three fast movements. Pressure pain thresholds (PPTs) were recorded bilaterally from neck, head and arm at baseline, after the third and sixth movement series. Pain intensity was recorded on an electronic visual analogue scale (VAS). Larger pain areas and higher VAS scores were found in patients compared with controls (p < 0.001), and in patients, the VAS scores increased in the course of movements (p < 0.02). PPTs were lower in patients compared with controls at all sites (p < 0.03), and these decreased during arm movements in the IONP group (p < 0.03), while increasing at head and neck sites in controls (p < 0.04). During the slow movements, increasing serratus anterior EMG activity was found in the series with short breaks in-between for the WAD group compared with IONP and controls (p < 0.001). Axioscapular movement caused different responses in pain sensitivity and muscle activity between neck pain patient groups compared with controls. Neck pain patients report increased symptoms following upper limb activities. This study shows that repeated arm movements caused differentiated responses in pain sensitivity and muscle activity between subgroups of neck pain patient and asymptomatic controls. Such findings may be of great clinical significance when planning rehabilitation for this patient population. © 2017 European Pain Federation - EFIC®.

Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.

PubMed

Taha, Omneya; Opitz, Thoralf; Mueller, Marcus; Pitsch, Julika; Becker, Albert; Evert, Bernd Oliver; Beck, Heinz; Jeub, Monika

2017-11-01

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the somata of nociceptive fibers, in a rat model of GBS (experimental autoimmune neuritis=EAN). EAN rats developed behavioral signs of neuropathic pain. This was accompanied by a significant shortening of action potentials due to a more rapid repolarization and an increase in repetitive firing in a subgroup of capsaicin-responsive DRG neurons. Na + current measurements revealed a significant increase of the fast TTX-sensitive current and a reduction of the persistent TTX-sensitive current component. These changes of Na + currents may account for the significant decrease in AP duration leading to an overall increase in excitability and are therefore possibly directly linked to pathological pain behavior. Thus, like in other animal models of neuropathic and inflammatory pain, Na + channels seem to be crucially involved in the pathology of GBS and may constitute promising targets for pain modulating pharmaceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

Improved foot sensitivity and pain reduction in patients with peripheral neuropathy after treatment with monochromatic infrared photo energy--MIRE.

PubMed

Harkless, Lawrence B; DeLellis, Salvatore; Carnegie, Dale H; Burke, Thomas J

2006-01-01

The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated.

Cuff Pressure Pain Detection Is Associated with Both Sex and Physical Activity Level in Nonathletic Healthy Subjects.

PubMed

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

2017-08-01

The aim of this study was to evaluate pressure pain sensitivity on leg and arm in 98 healthy persons (50 women) using cuff algometry. Furthermore, associations with sex and physical activity level were investigated. Normal physical activity level was defined as Godin Leisure-Time Exercise Questionnaire (GLTEQ) score ≤ 45 and high activity level as GLTEQ > 45. A pneumatic double-chamber cuff was placed around the arm or leg where a single chamber was inflated. The cuff inflation rate (1 kPa/s) was constant, and pain intensity was registered continuously on a 10 cm electronic visual analogue scale (VAS). The pain detection threshold (PDT) was defined as when the pressure was perceived as painful, and pain tolerance (PTT) was when the subject terminated the cuff inflation. For PTT, the corresponding VAS score was recorded (VAS-PTT). The protocol was repeated with two chambers inflated. Only single cuff results are given. For women compared with men, the PDT was lower when assessed in the arm ( P = 0.002), PTTs were lower in the arm and leg ( P < 0.001), and the VAS-PTT was higher in the arm and leg ( P < 0.033). Highly active participants compared with less active had higher PDT ( P = 0.027) in the leg. Women showed facilitated spatial summation ( P < 0.014) in the arm and leg and a steeper VAS slope (i.e., the slope of the VAS pressure curve between PDT and PPT) in the arm and leg ( P < 0.003). This study indicates that reduced pressure pain sensitivity is associated both with male sex and physical activity level. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

A cross-sectional survey to investigate the prevalence of pain in Japanese patients with major depressive disorder and schizophrenia.

PubMed

Kishi, Taro; Matsuda, Yuki; Mukai, Tomohiko; Matsunaga, Shinji; Yasue, Ichiro; Fujita, Kiyoshi; Okochi, Tomo; Hirano, Shigeki; Kajio, Yusuke; Funahashi, Toshihiko; Akamatsu, Kaku; Ino, Kei; Okuda, Momoko; Tabuse, Hideaki; Iwata, Nakao

2015-05-01

We conducted a cross-sectional survey to assess the prevalence of physical pain in Japanese major depressive disorder (MDD) and schizophrenia (SZ) patients as well as in healthy controls (HCs). We also examined the association between their psychopathology and characteristics of pain according to a face-to-face survey by an experienced psychiatrist and psychologist. We analyzed 233 HCs, 94 MDD patients, and 75 SZ patients using the McGill Pain Questionnaire (MPQ) and SF-8 (all participants), the Hamilton Depression Rating Scale 21 items (MDD patients), and the Positive and Negative Symptom Scale (SZ patients). Although MDD patients experienced more pain than HCs, there was no difference in the prevalence of pain between SZ patients and HCs. Moreover, HCs with pain did not have higher SF-8 total scores than those without pain, whereas both MDD and SZ patients with pain had higher SF-8 total scores than those without pain. The severity of psychopathology in MDD and SZ patients was also positively associated with both the prevalence of pain and MPQ scores. MPQ scores were also associated with positive symptoms in SZ patients. Considering these results, physicians need to query MDD patients about physical pain during examination if they are to ensure a favorable and quick response to treatment. The severity of positive symptoms (i.e., clinical status) in SZ patients might also be associated with pain sensitivity, and warrants further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Risk factors predicting the development of widespread pain from chronic back or neck pain

PubMed Central

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

2010-01-01

Emerging evidence suggests that some individuals with regional pain disorders go on to develop chronic widespread pain (CWP). However, the mechanism behind this transition and nature of risk factors that predispose a person to develop CWP remain to be elucidated. The purpose of this study was to describe the frequency with which participants with chronic back or neck pain develop CWP and to determine the risk factors associated with this development. In a sample of 512 individuals, we found that nearly a quarter (22.6%) of subjects who presented with regional back or neck pain in 2001/2002 had developed CWP by 2007. Logistic regression indicated that seven factors were associated with the transition to CWP: moderate or severe pain intensity, female gender, history of abuse, family history of CWP, severe interference with general activity, having one or more central sensitivity syndromes, and using more pain management strategies. History of abuse was not significant in multivariate analysis. Notably number of depressive symptoms endorsed, pain duration, age, body mass index, number of medication classes used, and receipt of disability benefits were not significantly associated with this transition. PMID:20488762

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2014-01-01

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

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

PubMed

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

2006-03-01

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

Mindfulness Is Associated with Increased Hedonic Capacity Among Chronic Pain Patients Receiving Extended Opioid Pharmacotherapy

PubMed Central

Thomas, Elizabeth A.; Garland, Eric L.

2016-01-01

Objectives Chronic pain and long-term opioid use may lead to a persistent deficit in hedonic capacity, characterized by increased sensitivity to aversive states and insensitivity to natural rewards. Dispositional mindfulness has been linked with improved emotion regulation and pain coping. The aim of the current study was to examine associations between dispositional mindfulness, hedonic capacity, and pain-related interference in an opioid-using chronic pain sample. Methods Data were obtained from a sample of 115 chronic pain patients on long-term opioid therapy (68% females, M age=48.3, SD=13.6) who completed the Five Facet Mindfulness Questionnaire (FFMQ), the Snaith Hamilton Anhedonia and Pleasure Scale (SHAPS), the Brief Pain Inventory (BPI), and a psychiatric assessment of major depression. Bivariate correlations, hierarchical multiple regression, and path analysis were used to determine if dispositional mindfulness scores (FFMQ) predicted variance in hedonic capacity (SHAPS), and if hedonic capacity mediated the association between mindfulness and pain interference. Results We observed a significant positive correlation between dispositional mindfulness and hedonic capacity scores, r=.33, p<.001. Hierarchical regression indicated that after controlling for pain interference and major depressive disorder diagnosis, dispositional mindfulness explained a significant portion of variance in hedonic capacity (Beta = .30, p< .01). The association between dispositional mindfulness and pain interference was mediated by hedonic capacity (b = −.011, SE=.005, 95% C.I. = −.004 to −.024, full model R2=.39). Discussion Findings indicate that dispositional mindfulness was associated with hedonic capacity among this chronic pain sample. In light of this association, it is plausible that interventions that increase mindfulness may reduce pain-related impairment among opioid-using patients by enhancing hedonic capacity. PMID:28060783

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

PubMed

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

2017-09-01

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

Therapeutic Targeting of TRPV1 for the Treatment of Chronic Pain Associated with Prostate Cancer Bone Metastasis

DTIC Science & Technology

2013-07-30

1 AD_________________ Award Number: W81XWH-11-1-0333 TITLE: Therapeutic Targeting of TRPV1 for the...TITLE AND SUBTITLE Therapeutic Targeting of TRPV1 for the Treatment of Chronic Pain 5a. CONTRACT NUMBER Associated with Prostate Cancer Bone...specific inflammatory factors, IL-6 and TNF-α, PTHrP and ET-1 on upregulation of TRPV1 channel function/expression, and nociceptor sensitization

Empathic Responsiveness in Amygdala and Anterior Cingulate Cortex in Youths with Psychopathic Traits

ERIC Educational Resources Information Center

Marsh, Abigail A.; Finger, Elizabeth C.; Fowler, Katherine A.; Adalio, Christopher J.; Jurkowitz, Ilana T. N.; Schechter, Julia C.; Pine, Daniel S.; Decety, Jean; Blair, R. J. R.

2013-01-01

Background: Psychopathic traits are associated with increases in antisocial behaviors such as aggression and are characterized by reduced empathy for others' distress. This suggests that psychopathic traits may also impair empathic pain sensitivity. However, whether psychopathic traits affect responses to the pain of others versus the self…

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

Pain sensitivity profiles in patients with advanced knee osteoarthritis

PubMed Central

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

2016-01-01

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

A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

PubMed

Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

2018-06-19

Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

PubMed

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

2015-12-01

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

Central mechanisms of stress-induced headache.

PubMed

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

2010-03-01

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

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

PubMed

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

2015-01-01

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

Drama-induced affect and pain sensitivity.

PubMed

Zillmann, D; de Wied, M; King-Jablonski, C; Jenzowsky, S

1996-01-01

This study was conducted to examine the pain-ameliorating and pain-sensitizing effects of exposure to emotionally engaging drama. Specifically, the consequences for pain sensitivity of exposure to dramatic expositions differing in both excitatory and hedonic qualities were determined. Hedonically negative, neutral, and positive affective states were induced in male respondents by exposure to excerpts from cinematic drama. Pain sensitivity was assessed by the cuff-pressure procedure before and after exposure and by the cold pressor test after exposure only. When compared against the control condition, pain sensitivity diminished under conditions of hedonically positive affect. An inverse effect was suggested for hedonically negative conditions, but proved tentative and statistically unreliable. The findings are consistent with earlier demonstrations of mood effects on pain sensitivity. Unlike inconclusive earlier findings concerning the magnitude of directional effects, however, they suggest an asymmetry that emphasizes the pain-ameliorating effect of positive affects while lending little, if any, support to the proposal of a pain-sensitizing effect of negative affects. The investigation did not accomplish the intended creation of conditions necessary to test the proposal that heightened sympathetic activity diminishes pain sensitivity. The utility of a rigorous determination of this hypothesized relationship is emphasized, and procedures for a viable test of the proposal are suggested.

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

PubMed

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

2017-09-01

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

Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.

PubMed

Singh, Jasvinder A; Noorbaloochi, Siamak; Knutson, Keith L

2017-01-14

There are few studies with an assessment of the levels of cytokines or neuropeptides as correlates of pain and pain relief in patients with painful joint diseases. Our objective was to assess whether improvements from baseline to 2-months in serum cytokine, chemokine and substance P levels were associated with clinically meaningful pain relief at 2-months post-injection in patients with painful total knee arthroplasty (TKA). Using data from randomized trial of 60 TKAs, we assessed the association of change in cytokine/chemokine/Substance P levels with primary study outcome, clinically important improvement in Western Ontario McMaster Osteoarthritis Index (WOMAC) pain subscale at 2-months post-injection using Student's t-tests and Spearman's correlation coefficient (non-parametric). Patients were categorized as pain responders (20-point reduction or more on 0-100 WOMAC pain) vs. pain non-responders. Sensitivity analysis used 0-10 daytime pain numeric rating scale (NRS) instead of WOMAC pain subscale. In a pilot study, compared to non-responders (n = 23) on WOMAC pain scale at 2-months, pain responders (n = 12) had significantly greater increase in serum levels of IL-7, IL-10, IL-12, eotaxin, interferon gamma and TNF-α from baseline to 2-months post-injection (p < 0.05 for all). Change in several cytokine/chemokine and substance P levels from pre-injection to 2-month follow-up correlated significantly with change in WOMAC pain with correlation coefficients ranging -0.37 to -0.51: IL-2, IL-7, IL-8, IL-9, IL-16, IL-12p, GCSF, IFN gamma, IP-10, MCP, MIP1b, TNF-α and VEGF (n = 35). Sensitivity analysis showed that substance P decreased significantly more from baseline to 2-months in the pain responders (0.54 ± 0.53; n = 10) than in the pain non-responders (0.48 ± 1.18; n = 9; p = 0.023) and that this change in serum substance P correlated significantly with change in daytime NRS pain, correlation coefficient was 0.53 (p = 0.021; n = 19). Findings should be interpreted with caution, since cytokine analyses were performed for a sub-group of the entire trial population. Serum cytokine, chemokine and Substance P levels correlated with pain response in patients with painful TKA after an intra-articular injection in a randomized trial.

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

Asymmetries in reciprocal baroreflex mechanisms and chronic pain severity: Focusing on irritable bowel syndrome.

PubMed

Davydov, D M; Naliboff, B; Shahabi, L; Shapiro, D

2018-02-01

Objective measures of pain severity remain ill defined, although its accurate measurement is critical. Reciprocal baroreflex mechanisms of blood pressure (BP) control were found to impact differently on pain regulation, and thus their asymmetry was hypothesized to also connect to chronic pain duration and severity. Seventy-eight female patients with irritable bowel syndrome (IBS) and 27 healthy women were assessed for IBS severity and chronicity, negative affect, and various measures of resting autonomic function including BP, heart rate and its variability (HRV), baroreceptor-sensitivity to activations and inhibitions, gains of brady- and tachy-cardiac baro-responses, gains of BP falls/rises, and BP start points for these spontaneous baroreflexes. IBS directly and indirectly (through increased negative affect) was associated with asymmetry between baroreceptor activations/inhibitions compared to symmetrical baroreflex reciprocity in the healthy women. In the IBS group, independently of specific IBS symptoms, pain chronicity was associated with (i) decreased BP falls coupled with either (a) decreased tachycardia associated with lower disease severity (earlier "pain resilience" mechanism), or (b) decreased bradycardia associated with higher disease severity (later "pain decompensation" mechanism), or (ii) increased BP start point for baroreceptor activations coupled with either (a) BP increase (delayed "pain adaptation" mechanism) or (b) affect-related HRV decrease (delayed "pain aggravation" mechanism). We anticipate the findings to be a starting point for validating these autonomic metrics of pain suffering and pain coping mechanisms in other chronic pain syndromes to suggest them as biomarkers of its severity and duration for profiling and correct management of chronic pain patients. © 2017 John Wiley & Sons Ltd.

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

PubMed

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

2017-10-01

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

Postoperative pain after haemorrhoidectomy: role of impaired evacuation.

PubMed

Puigdollers, A; Cisternas, D; Azpiroz, F

2011-08-01

We hypothesized that obstructive defaecation is associated with more postoperative pain after haemorrhoidectomy. Fifty patients with grade IV haemorrhoids were included in a prospective study. Impaired evacuation was defined as the inability to evacuate a rectal balloon. Perianal sensitivity was evaluated by means of an algometer, and anxiety and depression were assessed by the hospital anxiety and depression (HAD) scale. Over the first 10 days after a Milligan-Morgan haemorrhoidectomy, the following parameters were measured on daily questionnaires: pain (associated with and unrelated to defaecation by means of visual analogue scales), number of bowel movements, faecal consistency and analgesic requirement on demand (tramadol 50 mg p.o., number of doses). Results are expressed as median and interquartile range or mean ± SE. Patients with impaired evacuation (14 women, eight men; age range 28-61 years) experienced more postoperative pain than patients with nonimpaired evacuation (eight women, 20 men; age range 24-70 years): 3.2 (2.1) vs 2.1 (1.8) defaecatory pain, respectively (P = 0.045), and 2.4 (2.3) vs 1.7 (2.3) nondefecatory pain, respectively (P = 0.048). There was no difference between the groups regarding stool consistency, number of bowel movements [12.5 (7.3) vs 15.5 (7.2), respectively; NS] and analgesic requirement [1.0 (6.1) vs 1.0 (5.2) extra doses on demand, respectively; NS] during the 10 postoperative days. No differences related to age, sex, HAD scores or perianal sensitivity were found. Impaired anal evacuation is predictive of postoperative pain after haemorrhoidectomy. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

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

PubMed

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

2013-06-01

The effect of sexual arousal and orgasm on genital sensitivity has received little research attention, and no study has assessed sensation pleasurableness as well as painfulness. To clarify the relationship between sexual arousal, orgasm, and sensitivity in a healthy female sample. Twenty-six women privately masturbated to orgasm and almost to orgasm at two separate sessions, during which standardized pressure stimulation was applied to the glans clitoris, vulvar vestibule, and volar forearm at three testing times: (i) baseline; (ii) immediately following masturbation; and (iii) following a subsequent 15-minute rest period. Touch thresholds (tactile detection sensitivity), sensation pleasurableness ratings (pleasurable sensitivity), and pain thresholds (pain sensitivity). Pleasurableness ratings were higher on the glans clitoris than the vulvar vestibule, and at most testing times on the vulvar vestibule than the volar forearm; and at baseline and immediately after masturbation than 15 minutes later, mainly on the genital locations only. Pain thresholds were lower on the genital locations than the volar forearm, and immediately and 15 minutes after masturbation than at baseline. After orgasm, genital pleasurableness ratings and vulvar vestibular pain thresholds were lower than after masturbation almost to orgasm. Post-masturbation pleasurableness ratings were positively correlated with pain thresholds but only on the glans clitoris. Hormonal contraception users had lower pleasurableness ratings and pain thresholds on all locations than nonusers. There were no significant effects for touch thresholds. Masturbation appears to maintain pleasurable genital sensitivity but increase pain sensitivity, with lower genital pleasurable sensitivity and higher vulvar vestibular pain sensitivity when orgasm occurs. Findings suggest that enhancing stimulation pleasurableness, psychological sexual arousal and lubrication mitigate normative increases in pain sensitivity during sexual activity, and underscore the importance of measuring both pleasure and pain in sensation research. © 2013 International Society for Sexual Medicine.

Targeting G-Protein Signaling for the Therapeutics of Prostate Tumor Bone Metastases and the Associated Chronic Bone Pain

DTIC Science & Technology

2014-07-01

sensing receptor channels, such as TRPV1 , such that the channels are constitutively activated, leading to the sensation of chronic pain without any...Cancer Pain, Heterotrimeric G protein betagamma subunits, G protein coupled receptors (GPCRs), TRPV1 , Nociceptor Sensitization 3. Overall project...well as mediating GPCR-regulated TRPV1 channel function in cultured mouse sensory neurons (Aim 1). Major Goal/Objective 1: Determine the role of G

The prevalence of fibromyalgia in other chronic pain conditions.

PubMed

Yunus, Muhammad B

2012-01-01

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild.

The Prevalence of Fibromyalgia in Other Chronic Pain Conditions

PubMed Central

Yunus, Muhammad B.

2012-01-01

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild. PMID:22191024

Prevalence of dentine hypersensitivity and study of associated factors: a European population-based cross-sectional study.

PubMed

West, Nicola Xania; Sanz, Mariano; Lussi, Adrian; Bartlett, David; Bouchard, Phillipe; Bourgeois, Denis

2013-10-01

Dentine hypersensitivity (DH) manifests as a transient but arresting oral pain. The incidence is thought to be rising, particularly in young adults, due to increases in consumption of healthy, yet erosive, diets. This study aimed to assess the prevalence of DH and relative importance of risk factors, in 18-35 year old Europeans. In 2011, 3187 adults were enrolled from general dental practices in France, Spain, Italy, United Kingdom, Finland, Latvia and Estonia. DH was clinically evaluated by cold air tooth stimulation, patient pain rating (yes/no), accompanied by investigator pain rating (Schiff 0-3). Erosive toothwear (BEWE index 0-3) and gingival recession (mm) were recorded. Patients completed a questionnaire regarding the nature of their DH, erosive dietary intake and toothbrushing habits. 41.9% of patients reported pain on tooth stimulation and 56.8% scored ≥1 on Schiff scale for at least one tooth. Clinical elicited sensitivity was closely related to Schiff score and to a lesser degree, questionnaire reported sensitivity (26.8%), possibly reflecting the transient nature of the pain, alongside good coping mechanisms. Significant associations were found between clinically elicited DH and erosive toothwear and gingival recession. The questionnaire showed marked associations between DH and risk factors including heartburn/acid reflux, vomiting, sleeping medications, energy drinks, smoking and acid dietary intake. Overall, the prevalence of DH was high compared to many published findings, with a strong, progressive relationship between DH and erosive toothwear, which is important to recognise for patient preventive therapies and clinical management of DH pain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Do Subjects with Whiplash-Associated Disorders Respond Differently in the Short-Term to Manual Therapy and Exercise than Those with Mechanical Neck Pain?

PubMed

Castaldo, Matteo; Catena, Antonella; Chiarotto, Alessandro; Fernández-de-Las-Peñas, César; Arendt-Nielsen, Lars

2017-04-01

To compare the short-term effects of manual therapy and exercise on pain, related disability, range of motion, and pressure pain thresholds between subjects with mechanical neck pain and whiplash-associated disorders. Twenty-two subjects with mechanical neck pain and 28 with whiplash-associated disorders participated. Clinical and physical outcomes including neck pain intensity, neck-related disability, and pain area, as well as cervical range of motion and pressure pain thresholds over the upper trapezius and tibialis anterior muscles, were obtained at baseline and after the intervention by a blinded assessor. Each subject received six sessions of manual therapy and specific neck exercises. Mixed-model repeated measures analyses of covariance (ANCOVAs) were used for the analyses. Subjects with whiplash-associated disorders exhibited higher neck-related disability ( P  = 0.021), larger pain area ( P  = 0.003), and lower pressure pain thresholds in the tibialis anterior muscle ( P  = 0.009) than those with mechanical neck pain. The adjusted ANCOVA revealed no between-group differences for any outcome (all P  > 0.15). A significant main effect of time was demonstrated for clinical outcomes and cervical range of motion with both groups experiencing similar improvements (all P  < 0.01). No changes in pressure pain thresholds were observed in either group after treatment ( P  > 0.222). The current clinical trial found that subjects with mechanical neck pain and whiplash-associated disorders exhibited similar clinical and neurophysiological responses after a multimodal physical therapy intervention, suggesting that although greater signs of central sensitization are present in subjects with whiplash-associated disorders, this does not alter the response in the short term to manual therapy and exercises. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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

PubMed

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

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

Peripheral input and its importance for central sensitization.

PubMed

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

2013-11-01

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

Brain-Heart Pathways to Blood Pressure-Related Hypoalgesia.

PubMed

Ottaviani, Cristina; Fagioli, Sabrina; Mattei, Eugenio; Censi, Federica; Edwards, Louisa; Macaluso, Emiliano; Bozzali, Marco; Critchley, Hugo; Calcagnini, Giovanni

2018-03-28

High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is implicated. We examined normotensives using functional neuroimaging (fMRI) and pain stimulation during distinct phases of the cardiac cycle to test the hypothesized neural mediation of baroreceptor-induced attenuation of pain. Eighteen participants (10 women; 32.7 ± 6.5 years) underwent BP monitoring over one week at home, and individual pain thresholds were determined in the lab. Subsequently, participants were administered unpredictable painful and non-painful electrocutaneous shocks (stimulus type), timed to occur either at systole or diastole (cardiac phase) in an event-related design. After each trial, participants evaluated their subjective experience. Subjective pain was lower for painful stimuli administered at systole compared to diastole, F1, 2283 = 4.82; p = 0.03. Individuals with higher baseline BP demonstrated overall lower pain perception, F1, 2164 = 10.47; p < 0.0001. Within the brain, painful stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex, posterior insula, amygdala, and the thalamus. Stimuli delivered during systole (concurrent with baroreceptor discharge) activated areas associated with heightened parasympathetic drive. No stimulus type x cardiac phase interaction emerged except for a small cluster located in the right parietal cortex. We confirm the negative associations between BP and pain, highlighting the antinociceptive impact of baroreceptor discharge. Neural substrates associated with baroreceptor/BP-related hypoalgesia include superior parietal lobule, precentral and lingual gyrus, regions typically involved in the cognitive aspects of pain experience.

Association of different levels of depressive symptoms with symptomatology, overall disease severity, and quality of life in women with fibromyalgia.

PubMed

Soriano-Maldonado, Alberto; Amris, Kirstine; Ortega, Francisco B; Segura-Jiménez, Víctor; Estévez-López, Fernando; Álvarez-Gallardo, Inmaculada C; Aparicio, Virginia A; Delgado-Fernández, Manuel; Henriksen, Marius; Ruiz, Jonatan R

2015-12-01

This study examined the associations of different levels of depression with pain, sleep quality, fatigue, functional exercise capacity, overall fibromyalgia (FM) severity, and health-related quality of life (HRQoL) in women with FM. A total of 451 women with FM participated in this cross-sectional study. Depressive symptoms (Beck Depression Inventory; BDI-II), pain intensity (numerical rating scale; NRS), pain sensitivity (algometry), sleep quality (Pittsburgh Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), functional exercise capacity (6-min walk test), FM severity (revised Fibromyalgia Impact Questionnaire), and HRQoL (SF-36) were assessed. Participants with severe depressive symptoms had significantly higher pain intensity (NRS = 1.1; 95 % CI 0.3-1.8), fatigue (12.6-units; 95 % CI 8.2-17.1) and overall FM severity (12.6-units; 95 % CI 11.4-23.7), as well as poorer sleep quality (3.2-units; 95 % CI 1.7-4.7) and mental component of HRQoL (-17.0-units; 95 % CI -21.0 to -12.9) than participants with minimal signs of depression. There was no association of signs of depression with pain sensitivity, exercise capacity, or the physical component of HRQoL (P > 0.05). These results extend current knowledge on the association of signs of depression with FM severity and quality of life in women with FM, and suggest that severity of depressive symptoms could potentially be a prognostic factor to be considered in future prospective intervention studies.

Protocol for a placebo-controlled, within-participants crossover trial evaluating the efficacy of intranasal oxytocin to improve pain and function among women with chronic pelvic musculoskeletal pain.

PubMed

Rash, Joshua A; Toivonen, Kirsti; Robert, Magali; Nasr-Esfahani, Maryam; Jarrell, John F; Campbell, Tavis S

2017-04-16

This protocol presents the rationale and design for a trial evaluating the efficacy of intranasal oxytocin in improving pain and function among women with chronic pelvic musculoskeletal pain. Oxytocin is a neuropeptide traditionally recognised for involvement in labour, delivery and lactation. Novel evidence suggests that oxytocin decreases pain sensitivity in humans. While oxytocin administration has been reported to lower pain sensitivity among patients experiencing chronic back pain, headache, constipation and colon pain, no research has evaluated the association between intranasal oxytocin and chronic pelvic musculoskeletal pain. The association between oxytocin and pain may differ in women with chronic pelvic musculoskeletal pain relative to other chronic pain conditions because of the abundance of oxytocin receptors in the uterus. This is a prospective, randomised, placebo-controlled, double-blind, within-participants crossover trial. 50 women with chronic pelvic musculoskeletal pain will be recruited through a local chronic pain centre and gynaecology clinics. Women will complete baseline measures and be randomised to an experimental or control condition that involve 2 weeks of self-administering twice-daily doses of 24 IU intranasal oxytocin or placebo, respectively. Women will then undergo a 2-week washout period before crossing over to receive the condition that they had not yet received. The primary outcome will be pain and function measured using the Brief Pain Inventory-Short Form. Secondary outcomes include emotional function, sleep disturbance and global impression of change. This trial will provide data on the 14-day safety and side-effect profile of intranasal oxytocin self-administered as an adjuvant treatment for chronic pelvic musculoskeletal pain. This trial was granted approval from Health Canada and the University of Calgary Conjoint Health Research Ethics Board, and is registered online at ClinicalTrials.gov (#NCT02888574). Results will be disseminated to healthcare professionals through peer-reviewed publications and to the general public through press releases. NCT02888574; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

PubMed

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

2016-08-01

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

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain.

PubMed

Moloney, Rachel D; Golubeva, Anna V; O'Connor, Richard M; Kalinichev, Mikhail; Dinan, Timothy G; Cryan, John F

2015-01-01

Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8) are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY) rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

PubMed Central

Moloney, Rachel D.; Golubeva, Anna V.; O'Connor, Richard M.; Kalinichev, Mikhail; Dinan, Timothy G.; Cryan, John F.

2015-01-01

Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8) are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY) rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need. PMID:26844237

Predictive value of painful popping for a posterior root tear of the medial meniscus in middle-aged to older Asian patients.

PubMed

Bae, Ji-Hoon; Paik, Nak Hwan; Park, Gyu-Won; Yoon, Jung-Ro; Chae, Dong-Ju; Kwon, Jae Ho; Kim, Jong In; Nha, Kyung-Wook

2013-03-01

The purpose of this study was to determine the accuracy, sensitivity, specificity, and predictive values of a single event of painful popping in the presence of a posterior root tear of the medial meniscus in middle-aged to older Asian patients. We conducted a retrospective review of medical records of 936 patients who underwent arthroscopic surgeries for an isolated medial meniscus tear between January 2000 and December 2010. There were 332 men and 604 women with a mean age of 41 years (range, 25 to 66 years). The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of a painful popping sensation for a posterior root tear of the medial meniscus were calculated. Arthroscopy confirmed the presence of posterior root tears of the medial menisci in 237 of 936 patients (25.3%). A single event of a painful popping sensation was present in 86 of these 936 patients (9.1%). Of these 86 patients with a painful popping sensation, 83 (96.5%) were categorized as having an isolated posterior root tear of the medial meniscus. The positive predictive value of a painful popping sensation in identifying a posterior root tear of the medial meniscus was 96.5%, the negative predictive value was 81.8%, the sensitivity was 35.0%, the specificity was 99.5%, and the diagnostic accuracy was 77.9%. A single event of painful popping can be a highly predictive clinical sign of a posterior root tear of the medial meniscus in the middle-aged to older Asian population. However, it has low sensitivity for the detection of a posterior root tear of the medial meniscus. Level IV, therapeutic case series. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Costs of pleasure and the benefits of pain: self-perceived genital sensation, anatomy and sexual dysfunction.

PubMed

Callens, Nina; Bronselaer, Guy; De Sutter, Petra; De Cuypere, Griet; T'Sjoen, Guy; Hoebeke, Piet; Cools, Martine

2016-02-01

Background Research has highlighted the complex association between female sexual dysfunction (FSD) and distress regarding sexual activity, with decreased physical pleasure being an important mediator. The current study aims to elucidate the association between pleasurable and painful genital sensitivity and FSD, and to further investigate whether FSD may be distressing because it prevents the experience of sexual pleasure, induces pain or both. Sexually active women (n=256; median, 22 years; range, 18-49 years) completed web-based questionnaires, including the Self-Assessment of Genital Anatomy and Sexual Function, the Female Sexual Function Index and the Female Sexual Distress Scale. Women reported their clitoris to be more sensitive than their vagina in terms of having more pleasurable responses (P<0.001), but not more painful responses (P=0.49). In women with FSD (n=36), impaired self-perceived genital sensation was found: they reported significantly less sexual pleasure and orgasm intensity, and more orgasm effort and discomfort within the clitoral and vaginal area than women without FSD (n=220) (P-value<0.05). The odds of having FSD were significantly greater in women with perceived increased discomfort in the vaginal area during stimulation (odds ratio=5.59, P=0.009, 95% confidence interval: 1.53-20.39), but not in the clitoral area. The data provide evidence of the relevance of self-perceived genital sensitivity to sexual pleasure and overall sexual experience. Enhancing the pleasurableness of genital sensations, especially during partnered sex, could decrease the likelihood of experiencing pain and concomitant FSD.

Machine-learned analysis of quantitative sensory testing responses to noxious cold stimulation in healthy subjects.

PubMed

Weyer-Menkhoff, I; Thrun, M C; Lötsch, J

2018-05-01

Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers. The probability density distribution was analysed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM), emergent self-organizing maps and self-organizing swarms of data agents. The probability density function of pain responses was trimodal (mean thresholds at 25.9, 18.4 and 8.0 °C for tonic and 24.5, 18.1 and 7.5 °C for phasic stimuli). Subjects' association with Gaussian modes was consistent between both types of stimuli (weighted Cohen's κ = 0.91). Patterns emerging in self-organizing neuronal maps and swarms could be associated with different trends towards decreasing cold pain sensitivity in different Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as particularly distinct. Thresholds at, roughly, 25 and 18 °C agree with known working temperatures of TRPM8 and TRPA1 ion channels, respectively, and hint at relative local dominance of either channel in respective subjects. Data patterns suggest involvement of further distinct mechanisms in cold pain perception at lower temperatures. Findings support data science approaches to identify biologically plausible hints at complex molecular mechanisms underlying human pain phenotypes. Sensitivity to pain is heterogeneous. Data-driven computational research approaches allow the identification of subgroups of subjects with a distinct pattern of sensitivity to cold stimuli. The subgroups are reproducible with different types of noxious cold stimuli. Subgroups show pattern that hints at distinct and inter-individually different types of the underlying molecular background. © 2018 European Pain Federation - EFIC®.

A magnetoencephalography study of visual processing of pain anticipation.

PubMed

Machado, Andre G; Gopalakrishnan, Raghavan; Plow, Ela B; Burgess, Richard C; Mosher, John C

2014-07-15

Anticipating pain is important for avoiding injury; however, in chronic pain patients, anticipatory behavior can become maladaptive, leading to sensitization and limiting function. Knowledge of networks involved in pain anticipation and conditioning over time could help devise novel, better-targeted therapies. With the use of magnetoencephalography, we evaluated in 10 healthy subjects the neural processing of pain anticipation. Anticipatory cortical activity elicited by consecutive visual cues that signified imminent painful stimulus was compared with cues signifying nonpainful and no stimulus. We found that the neural processing of visually evoked pain anticipation involves the primary visual cortex along with cingulate and frontal regions. Visual cortex could quickly and independently encode and discriminate between visual cues associated with pain anticipation and no pain during preconscious phases following object presentation. When evaluating the effect of task repetition on participating cortical areas, we found that activity of prefrontal and cingulate regions was mostly prominent early on when subjects were still naive to a cue's contextual meaning. Visual cortical activity was significant throughout later phases. Although visual cortex may precisely and time efficiently decode cues anticipating pain or no pain, prefrontal areas establish the context associated with each cue. These findings have important implications toward processes involved in pain anticipation and maladaptive pain conditioning. Copyright © 2014 the American Physiological Society.

Learning to predict and control harmful events: chronic pain and conditioning.

PubMed

Vlaeyen, Johan W S

2015-04-01

Pain is a biologically relevant signal and response to bodily threat, associated with the urge to restore the integrity of the body. Immediate protective responses include increased arousal, selective attention, escape, and facial expressions, followed by recuperative avoidance and safety-seeking behaviors. To facilitate early and effective protection against future bodily threat or injury, learning takes place rapidly. Learning is the observable change in behavior due to events in the internal and external environmental and includes nonassociative (habituation and sensitization) and associative learning (Pavlovian and operant conditioning). Once acquired, these knowledge representations remain stored in memory and may generalize to perceptually or functionally similar events. Moreover, these processes are not just a consequence of pain; they may directly influence pain perception. In contrast to the rapid acquisition of learned responses, their extinction is slow, fragile, context dependent and only occurs through inhibitory processes. Here, we review features of associative forms of learning in humans that contribute to pain, pain-related distress, and disability and discuss promising future directions. Although conditioning has a long and honorable history, a conditioning perspective still might open new windows on novel treatment modalities that facilitate the well-being of individuals with chronic pain.

The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study.

PubMed

Suskind, Anne M; Berry, Sandra H; Ewing, Brett A; Elliott, Marc N; Suttorp, Marika J; Clemens, J Quentin

2013-01-01

As part of the RICE (RAND Interstitial Cystitis Epidemiology) study, we developed validated case definitions to identify interstitial cystitis/bladder pain syndrome in women and chronic prostatitis/chronic pelvic pain syndrome in men. Using population based screening methods, we applied these case definitions to determine the prevalence of these conditions in men. A total of 6,072 households were contacted by telephone to screen for men who had symptoms of interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome. An initial 296 men screened positive, of whom 149 met the inclusionary criteria and completed the telephone interview. For interstitial cystitis/bladder pain syndrome 2 case definitions were applied (1 with high sensitivity and 1 with high specificity), while for chronic prostatitis/chronic pelvic pain syndrome a single case definition (with high sensitivity and specificity) was used. These case definitions were used to classify subjects into groups based on diagnosis. The interstitial cystitis/bladder pain syndrome weighted prevalence estimates for the high sensitivity and high specificity definitions were 4.2% (3.1-5.3) and 1.9% (1.1-2.7), respectively. The chronic prostatitis/chronic pelvic pain syndrome weighted prevalence estimate was 1.8% (0.9-2.7). These values equate to 1,986,972 (95% CI 966,042-2,996,924) men with chronic prostatitis/chronic pelvic pain syndrome and 2,107,727 (95% CI 1,240,485-2,974,969) men with the high specificity definition of interstitial cystitis/bladder pain syndrome in the United States. The overlap between men who met the high specificity interstitial cystitis/bladder pain syndrome case definition or the chronic prostatitis/chronic pelvic pain syndrome case definition was 17%. Symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome are widespread among men in the United States. The prevalence of interstitial cystitis/bladder pain syndrome symptoms in men approaches that in women, suggesting that this condition may be underdiagnosed in the male population. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Associations of Varus Thrust and Alignment with Pain in Knee Osteoarthritis

PubMed Central

Lo, Grace H.; Harvey, William F.; McAlindon, Timothy E.

2012-01-01

Objective To compare associations of varus thrust and varus static alignment with pain in those with knee osteoarthritis (OA). Method This was a cross-sectional study of participants from a randomized controlled trial of vitamin D for knee OA. Participants were video recorded walking and scored for presence of varus thrust. Standard PA knee X-rays were measured for static alignment. Pain questions from the Western Ontario McMasters Osteoarthritis (WOMAC) questionnaire assessed symptoms. We calculated means for total WOMAC pain by varus thrust and varus alignment (i.e. corrected anatomic alignment < 178°). We performed ordinal logistic regressions; outcomes: individual WOMAC pain questions; predictors: varus thrust and varus alignment. Results There were 82 participants, mean age 65.1 (±8.5), mean body mass index 30.2 (±5.4), and 60% female. Total WOMAC pain was 6.3 versus 3.9, p = 0.007 in those with versus without definite varus thrust. For varus alignment, total WOMAC pain was 5.2 versus 4.2, p = 0.30. Odds ratios for pain with walking and standing were 5.5 (95%CI 2.0 – 15.1) and 6.0 (95%CI 2.2 – 16.2) in those with versus without definite varus thrust. There were no significant associations between varus alignment and individual WOMAC pain questions. Sensitivity analyses suggested a more stringent definition of varus might have been associated with walking and standing pain. Conclusion In those with knee OA, varus thrust and possibly varus static alignment, were associated with pain, specifically during weight-bearing activities. Treatment of varus thrust (e.g. via bracing or gait modification) may lead to improvement of symptoms. PMID:22307813

The association between dry needling-induced twitch response and change in pain and muscle function in patients with low back pain: a quasi-experimental study.

PubMed

Koppenhaver, Shane L; Walker, Michael J; Rettig, Charles; Davis, Joel; Nelson, Chenae; Su, Jonathan; Fernández-de-Las-Peñas, Cesar; Hebert, Jeffrey J

2017-06-01

To investigate the relationship between dry needling-induced twitch response and change in pain, disability, nociceptive sensitivity, and lumbar multifidus muscle function, in patients with low back pain (LBP). Quasi-experimental study. Department of Defense Academic Institution. Sixty-six patients with mechanical LBP (38 men, 28 women, age: 41.3 [9.2] years). Dry needling treatment to the lumbar multifidus muscles between L3 and L5 bilaterally. Examination procedures included numeric pain rating, the Modified Oswestry Disability Index, pressure algometry, and real-time ultrasound imaging assessment of lumbar multifidus muscle function before and after dry needling treatment. Pain pressure threshold (PPT) was used to measure nocioceptive sensitivity. The percent change in muscle thickness from rest to contraction was calculated to represent muscle function. Participants were dichotomized and compared based on whether or not they experienced at least one twitch response on the most painful side and spinal level during dry needling. Participants experiencing local twitch response during dry needling exhibited greater immediate improvement in lumbar multifidus muscle function than participants who did not experience a twitch (thickness change with twitch: 12.4 [6]%, thickness change without twitch: 5.7 [11]%, mean difference adjusted for baseline value, 95%CI: 4.4 [1 to 8]%). However, this difference was not present after 1-week, and there were no between-groups differences in disability, pain intensity, or nociceptive sensitivity. The twitch response during dry needling might be clinically relevant, but should not be considered necessary for successful treatment. Published by Elsevier Ltd.

Algogenic substances and metabolic status in work-related Trapezius Myalgia: a multivariate explorative study.

PubMed

Gerdle, Björn; Kristiansen, Jesper; Larsson, Britt; Saltin, Bengt; Søgaard, Karen; Sjøgaard, Gisela

2014-10-28

This study compares the levels of algesic substances between subjects with trapezius myalgia (TM) and healthy controls (CON) and explores the multivariate correlation pattern between these substances, pain, and metabolic status together with relative blood flow changes reported in our previous paper (Eur J Appl Physiol 108:657-669, 2010). 43 female workers with (TM) and 19 females without (CON) trapezius myalgia were - using microdialysis - compared for differences in interstitial concentrations of interleukin-6 (IL-6), bradykinin (BKN), serotonin (5-HT), lactate dehydrogenas (LDH), substance P, and N-terminal propeptide of procollagen type I (PINP) in the trapezius muscle at rest and during repetitive/stressful work. These data were also used in multivariate analyses together with previously presented data (Eur J Appl Physiol 108:657-669, 2010): trapezius muscle blood flow, metabolite accumulation, oxygenation, and pain development and sensitivity. Substance P was significantly elevated in TM (p=0.0068). No significant differences were found in the classical algesic substances (p: 0.432-0.926). The multivariate analysis showed that blood flow related variables, interstitial concentrations of metabolic (pyruvate), and algesic (BKN and K+) substances were important for the discrimination of the subjects to one of the two groups (R2: 0.19-0.31, p<0.05). Pain intensity was positively associated with levels of 5-HT and K+ and negatively associated with oxygenation indicators and IL-6 in TM (R2: 0.24, p<0.05). A negative correlation existed in TM between mechanical pain sensitivity of trapezius and BKN and IL-6 (R2: 0.26-0.39, p<0.05). The present study increased understanding alterations in the myalgic muscle. When considering the system-wide aspects, increased concentrations of lactate, pyruvate and K+ and decreased oxygenation characterized TM compared to CON. There are three major possible explanations for this finding: the workers with pain had relatively low severity of myalgia, metabolic alterations preceded detectable alterations in levels of algesics, or peripheral sensitization and other muscle alterations existed in TM. Only SP of the investigated algesic substances was elevated in TM. Several of the algesics were of importance for the levels of pain intensity and mechanical pain sensitivity in TM. These results indicate peripheral contribution to maintenance of central nociceptive and pain mechanisms and may be important to consider when designing treatments.

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

PubMed

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

2015-10-01

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

Altered Pain Sensitivity in Elderly Women with Chronic Neck Pain

PubMed Central

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

2015-01-01

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

Trunk kinematics and low back pain during pruning among vineyard workers—A field study at the Chateau Larose-Trintaudon

PubMed Central

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

2017-01-01

The prevalence of low back disorders is dramatically high in viticulture. Field measurements that objectively quantify work exposure can provide information on the relationship between the adopted trunk postures and low back pain. The purposes of the present study were three-fold (1) to carry out a kinematics analysis of vineyard-workers’ pruning activity by extracting the duration of bending and rotation of the trunk, (2) to question separately the relationship between the duration of forward bending or trunk rotation with low back pain intensity and pressure pain sensitivity and (3) to question the relationship between the combined duration of forward bending and trunk rotation on low back pain intensity and pressure pain sensitivity. Fifteen vineyard-workers were asked to perform pruning activity for 12 minutes with a wireless triaxial accelerometer placed on their trunk. Kinematic analysis of the trunk showed that vineyard-workers spent more than 50% of the time with the trunk flexed greater than 30° and more than 20% with the trunk rotated greater than 10°. These results show that pruning activity lead to the adoption of forward bended and rotated trunk postures that could significantly increase the risk of work related musculoskeletal disorders in the low back. However, this result was mitigated by the observation of an absence of significant association between the duration of forward bending and trunk rotation with low back pain intensity or pressure pain sensitivity. Even if prospective field measurements and studies assessing the effects of low back pain confounders are needed, this field study provides new genuine information on trunk kinematics during pruning activity. PMID:28384277

Experimentally induced central sensitization in the cervical spine evokes postural stiffening strategies in healthy young adults.

PubMed

Huntley, Andrew H; Srbely, John Z; Zettel, John L

2015-02-01

Dysequilibrium of cervicogenic origin can result from pain and injury to cervical paraspinal tissues post-whiplash; however, the specific physiological mechanisms still remain unclear. Central sensitization is a neuradaptive process which has been clinically associated with conditions of chronic pain and hypersensitivity. Strong links have been demonstrated between pain hypersensitivity and postural deficits post-whiplash; however, the precise mechanisms are still poorly understood. The purpose of this study was to explore the mechanisms of cervicogenic disequilibrium by investigating the effect of experimentally induced central sensitization in the cervical spine on postural stability in young healthy adults. Sixteen healthy young adults (7 males (22.6±1.13 years) and 9 females (22±2.69 years)) performed 30-s full-tandem stance trials on an AMTI force plate under normal and centrally sensitized conditions. The primary outcome variables included the standard deviation of the center of pressure (COP) position in medio-lateral (M-L) and antero-posterior (A-P) directions; sway range of the COP in M-L and A-P directions and the mean power frequency (MPF) of the COP and horizontal ground shear forces. Variability and sway range of the COP decreased with experimental induction of central sensitization, accompanied by an increase in MPF of COP displacement in both M-L and A-P directions, suggesting an increase in postural stiffening post-sensitization versus non-sensitized controls. Future studies need to further explore this relationship in clinical (whiplash, chronic pain) populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Musculoskeletal Pain, Self-reported Physical Function, and Quality of Life in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Cohort.

PubMed

Bout-Tabaku, Sharon; Michalsky, Marc P; Jenkins, Todd M; Baughcum, Amy; Zeller, Meg H; Brandt, Mary L; Courcoulas, Anita; Buncher, Ralph; Helmrath, Michael; Harmon, Carroll M; Chen, Mike K; Inge, Thomas H

2015-06-01

Obesity is associated with chronic musculoskeletal pain and is a risk factor for disability and osteoarthritis. To describe the prevalence, sites, and intensity of musculoskeletal pain in adolescents with severe obesity; to evaluate associations between musculoskeletal pain and self-reported physical function as well as weight-related quality of life; and to evaluate the association between musculoskeletal pain and high-sensitivity C-reactive protein level. Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) is a prospective, observational study that collects standardized data on adolescents undergoing weight loss surgery at 5 US centers. We examined baseline data from this cohort between February 28, 2007, and December 30, 2011. We excluded adolescents with Blount disease and slipped capital femoral epiphyses. A total of 233 participants were included in these analyses. We assessed musculoskeletal pain and pain intensity of the lower back, hips, knees, and ankles/feet using the visual analog scale, categorizing musculoskeletal pain into lower back pain, lower extremity (hips, knees, and feet/ankles combined) pain, and no pain. We assessed self-reported physical function status with the Health Assessment Questionnaire Disability Index and assessed weight-related quality of life with the Impact of Weight on Quality of Life-Kids measure. We adjusted for sex, race, age at surgery, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and clinical depressive symptoms in regression analyses. Among the 233 participants, the mean (SD) age at surgery was 17.1 (1.56) years and the median BMI was 50.4. Participants were predominantly female (77%), white (73%), and non-Hispanic (93%). Among the participants, 49% had poor functional status and 76% had musculoskeletal pain. Lower back pain was prevalent (63%), followed by ankle/foot (53%), knee (49%), and hip (31%) pain; 26% had pain at all 4 sites. In adjusted analyses, compared with pain-free participants, those reporting lower extremity pain had greater odds of having poor physical function according to scores on the Health Assessment Questionnaire Disability Index (odds ratio = 2.82; 95% CI, 1.35 to 5.88; P < .01). Compared with pain-free participants, those reporting lower extremity pain had significantly lower Impact of Weight on Quality of Life-Kids total scores (β = -9.42; 95% CI, -14.15 to -4.69; P < .01) and physical comfort scores (β = -17.29; 95% CI, -23.32 to -11.25; P < .01). After adjustment, no significant relationship was observed between musculoskeletal pain and high-sensitivity C-reactive protein level. Adolescents with severe obesity have musculoskeletal pain that limits their physical function and quality of life. Longitudinal follow-up will reveal whether weight loss surgery reverses pain and physical functional limitations and improves quality of life.

Neurotrophins and Migraine.

PubMed

Martins, L B; Teixeira, A L; Domingues, R B

2017-01-01

Neurotrophins (NTs) have been implicated in generation and modulation of nociceptive pathways. Change in NTs levels is associated with painful conditions and neurological diseases such as migraine. Currently, it is generally recognized that migraine headaches result from the activation and sensitization of trigeminal sensory afferent fibers leading to neuropeptides release such as calcitonin gene-related peptide (CGRP) and substance P (SP). This triggers an inflammatory cascade causing a neurogenic inflammation. The agents responsible for trigeminal activation and release of neuropeptides are still unclear. It is known that the transient receptor potential vanilloid receptor-1 (TRPV1) is an important mediator of CGRP and SP release. TRPV1 is closely associated with tyrosine receptors kinases (Trk), which are NTs receptors. NTs can act on TRPV1 increasing its sensitivity to painful stimuli, therefore predisposing to hyperalgesia. Upregulation of ion channels and pain receptors in dorsal root ganglion neurons may be alternative mechanisms by which NTs contribute to pain development. Only a few studies have been performed to investigate the role of NTs in migraine. These studies have reported changes in NTs levels in migraine patients either during the migraine attack or in free-headache periods. © 2017 Elsevier Inc. All rights reserved.

Central sensitization: Implications for the diagnosis and treatment of pain

PubMed Central

Woolf, Clifford J

2010-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2014-07-01

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

Can heterogeneity of chronic sickle-cell disease pain be explained by genomics? A literature review.

PubMed

Adegbola, Maxine A

2009-07-01

This literature review explores the potential of genomics to explain, or at least contribute to the discussion about, heterogeneity in chronic pain in sickle-cell disease (SCD). Adults with SCD, a single-gene disorder, are living longer than in years past, yet report being burdened by chronic pain. With only a few studies on chronic pain in this population, the epidemiology is unclear. However, research in the area of pain genetics continues to advance since the conclusion of the Human Genome Project. Two pain susceptibility genes, catechol-O-methyltransferase (COMT) and cytochrome P450, have, to date, been discovered that can increase individual susceptibility to the development of chronic pain. A search was conducted in PubMed, CINAHL, and EBSCO using the terms "sickle cell,'' "chronic pain,'' "polymorphism,'' "genetics,'' "pain genetics,'' "human,'' "adult,'' "association studies,'' and "pain susceptibility genes'' to search for articles published between 1970 and 2008. Chronic pain generally is more prevalent and severe than previously reported, and individuals with SCD report daily pain. The genomic era has made it possible for scientists to identify pain susceptibility genes that contribute to variability in the interindividual experience of chronic pain. Nurses are well positioned to generate and translate genomic research, thus improving care delivery. Such research may lead to the identification of polymorphisms associated with pain sensitivity in individuals with SCD.

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

PubMed

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

1994-09-01

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

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

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo

2014-01-01

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

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

PubMed

Wachholtz, Amy; Gonzalez, Gerardo

2014-12-01

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

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

PubMed

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

2018-05-17

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

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

PubMed

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

2010-04-01

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

Using Publicly Reported Nursing-Sensitive Screening Indicators to Measure Hospital Performance: The Netherlands Experience in 2011.

PubMed

Stalpers, Dewi; van der Linden, Dimitri; Kaljouw, Marian J; Schuurmans, Marieke J

2016-01-01

Deliberate screening allows detection of health risks that are otherwise not noticeable and allows expedient intervention to minimize complications and optimize outcomes, especially during critical events like hospitalization. Little research has evaluated the usefulness of screening performance and outcome indicators as measures to differentiate nursing quality, although policymakers are using them to benchmark hospitals. The aims of this study were to examine hospital performance based on nursing-sensitive screening indicators and to assess associations with hospital characteristics and nursing-sensitive outcomes for patients. A secondary use of nursing-sensitive data from the Dutch Health Care Inspectorate was performed, including the mandatory screening and outcome indicators related to delirium, malnutrition, pain and pressure ulcers. The sample consisted of all 93 hospitals in the Netherlands in 2011. High- and low-performing hospitals were determined based on the overall proportion of screened patients. Descriptive statistics and analysis of variance were used to examine screening performances in relation to hospital characteristics and nursing-sensitive outcomes. Over all hospitals, the average screening rates ranged from 59% (delirium) to 94% (pain). Organizational characteristics were not different in high- and low-performing hospitals. The hospitals with the best overall screening performances had significantly better results regarding protein intake within malnourished patients (p < .01). For mortality, marginal significant effects did not remain after controlling for organizational structures. No associations were found with prevalence of pressure ulcers and patient self-reported pain scores. The screening for patient risks is an important nursing task. Our findings suggest that nursing-sensitive screening indicators may be relevant measures for benchmarking nursing quality in hospitals. Time-trend studies are required to support our findings and to further investigate relations with nursing-sensitive outcomes.

Detection of changes in SEMG signals with myofascial pain using the pattern-classifier

NASA Astrophysics Data System (ADS)

Jiang, Ching-Fen; Huang, Pao-Tieh

2013-10-01

Myofascial pain on the upper back (MFPUB) has been a common occupational hazard associated with consistent computer use. Investigations into any sort neuromuscular functional changes due to myofascial pain are rare. This study aims to differentiate the wavelet energy patterns of the surface electromyography signals measured from 30 normal and 26 patient subjects using the K-means clustering process. The results show that the wavelet energy pattern of patient subjects was different to that of normal subject and reveals a sensitivity of 57.69% at a specificity of 76.67% in the identification of myofascial pain. Therefore, this model could provide a reliable feature for clinical diagnosis of myofascial pain.

Incomplete response to artificial tears is associated with features of neuropathic ocular pain.

PubMed

Galor, Anat; Batawi, Hatim; Felix, Elizabeth R; Margolis, Todd P; Sarantopoulos, Konstantinos D; Martin, Eden R; Levitt, Roy C

2016-06-01

Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears. Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears. By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement. Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

PubMed

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

2017-02-01

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

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

PubMed

Knutson, Gary A

2002-02-01

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

Perceived racial discrimination, but not mistrust of medical researchers, predicts the heat pain tolerance of African Americans with symptomatic knee osteoarthritis.

PubMed

Goodin, Burel R; Pham, Quyen T; Glover, Toni L; Sotolongo, Adriana; King, Christopher D; Sibille, Kimberly T; Herbert, Matthew S; Cruz-Almeida, Yenisel; Sanden, Shelley H; Staud, Roland; Redden, David T; Bradley, Laurence A; Fillingim, Roger B

2013-11-01

Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans. It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli, which, in turn, could influence clinical pain severity. This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic Whites. Mistrust of medical researchers was also assessed given its potential to affect responses to the noxious stimuli. One-hundred and 30 (52% African American, 48% non-Hispanic White) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions. In session one, individuals provided demographic, socioeconomic, physical and mental health information. They completed questionnaires related to perceived lifetime frequency of racial discrimination and mistrust of medical researchers. In session two, individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity, particularly heat pain tolerance. African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical researchers compared with non-Hispanic Whites. Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic Whites. Mistrust of medical researchers did not significantly predict heat pain tolerance for either racial group. These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli.

Clinical effects of buprenorphine on open field behaviour and gait symmetry in healthy and lame weaned piglets.

PubMed

Meijer, Ellen; van Nes, Arie; Back, Willem; van der Staay, Franz Josef

2015-12-01

Lameness in pigs decreases animal welfare and economic profit for the farmer. An important reason for impaired welfare in lame animals is pain due to lameness. No direct measurement of pain is possible in animals, and methods to indirectly detect and quantify the amount of pain an animal is experiencing are urgently needed. In this study, two methods to assess pain associated with lameness in pigs were evaluated to determine if they were sensitive enough to detect a lameness reduction as an effect of an experimental analgesic medication. Asymmetry associated with lameness was objectively quantified using pressure mat kinetic parameters: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Locomotor activity was assessed in an open field test. A dose of 0.04 mg/kg buprenorphine, a strong analgesic, was used to treat 10 lame pigs, while eight other lame pigs, treated with physiological saline solution, served as controls. Buprenorphine decreased lameness-associated asymmetry for pressure mat LR (P = 0.002), VI (P = 0.003) and PVP (P = 0.001) and increased activity of the lame pigs in the open field (P = 0.023), while saline-treated animals did not show any changes in asymmetry and became less active in the open field (P <0.001). It was concluded that measurement of gait asymmetry by pressure mat analysis and locomotor activity in an open field test are both sensitive enough to detect the analgesic effects of buprenorphine when used to treat moderate to severe clinical pain in a relatively small group of affected pigs. The methods used in this study may also provide promising additional tools for future research into early pain recognition and lameness treatment in pigs. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

Bonnet, Adeline; Naveteur, Janick

2006-10-01

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

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

PubMed

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

2017-09-01

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

Treatment of Morbidity with Atypical Chest Pain

PubMed Central

Cott, Arthur

1987-01-01

The appropriate management of atypical chest pain requires an integration of medical and behavioural treatments. Unnecessary medicalization can increase morbidity. A sensitivity to the behavioural factors contributing to symptoms and disability may reduce both. The purpose of this paper is to provide physicians with a cognitive-behavioural perspective of the nature of morbidity and disability associated with chronic chest discomfort; some strategies for detecting heretofore unsuspected disability associated with chronic chest pain and related discomfort in patients with organic findings (both cardiac and non-cardiac), as well those with no identifiable disease process or organic cause; and some simple behavioural and cognitive-behavioural therapeutic techniques for treating and preventing such problems. PMID:21263912

Disrupted Self-Perception in People With Chronic Low Back Pain. Further Evaluation of the Fremantle Back Awareness Questionnaire.

PubMed

Wand, Benedict Martin; Catley, Mark Jon; Rabey, Martin Ian; O'Sullivan, Peter Bruce; O'Connell, Neil Edward; Smith, Anne Julia

2016-09-01

Several lines of evidence suggest that body perception is altered in people with chronic back pain. Maladaptive perceptual awareness of the back might contribute to the pain experience as well as serve as a target for treatment. The Fremantle Back Awareness Questionnaire (FreBAQ) is a simple questionnaire recently developed to assess back-specific altered self-perception. The aims of this study were to present the outcomes of a comprehensive evaluation of the questionnaire's psychometric properties and explore the potential relationships between body perception, nociceptive sensitivity, distress, and beliefs about back pain and the contribution these factors might play in explaining pain and disability. Two hundred fifty-one people with chronic back pain completed the questionnaire as well as a battery of clinical tests. The Rasch model was used to explore the questionnaires' psychometric properties and correlation and multiple linear regression analyses were used to explore the relationship between altered body perception and clinical status. The FreBAQ appears unidimensional with no redundant items, has minimal ceiling and floor effects, acceptable internal consistency, was functional on the category rating scale, and was not biased by demographic or clinical variables. FreBAQ scores were correlated with sensitivity, distress, and beliefs and were uniquely associated with pain and disability. Several lines of evidence suggest that body perception might be disturbed in people with chronic low back pain, possibly contributing to the condition and offering a potential target for treatment. The FreBAQ was developed as a quick and simple way of measuring back-specific body perception in people with chronic low back pain. The questionnaire appears to be a psychometrically sound way of assessing altered self-perception. The level of altered self-perception is positively correlated with pain intensity and disability as well as showing associations with psychological distress, pain catastrophization, fear avoidance beliefs, and lumbar pressure pain threshold. In this sample, it appears that altered self-perception might be a more important determinant of clinical severity than psychological distress, pain catastrophization, fear avoidance beliefs, or lumbar pressure pain threshold. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception

PubMed Central

Lindstedt, Fredrik; Karshikoff, Bianka; Schalling, Martin; Olgart Höglund, Caroline; Ingvar, Martin; Lekander, Mats; Kosek, Eva

2012-01-01

Background Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities. Methods Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C–49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed. Results Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged. Conclusion/Significance To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a ‘hypo- to hyperalgesic’ response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted. PMID:22952650

Neck Pain

MedlinePlus

... Keep me signed in Passwords are Case Sensitive. Ex. Enter smith as follows: Smith Forgot Username/Password? ... Erythematosus (Juvenile) Takayasu's Arteritis Tendinitis & Bursitis Tumor Necrosis Factor Receptor Associated Periodic Syndrome (Juvenile) Vasculitis Enfermedades y ...

Anorectal and Pelvic Pain

PubMed Central

Bharucha, Adil E.; Lee, Tae Hee

2016-01-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the three most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first two conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacologic, behavioral, and physical therapy. Opioids should not be avoided, and surgery has a limited role, primarily in refractory interstitial cystitis. PMID:27712641

Beyond the classic eicosanoids: Peripherally-acting oxygenated metabolites of polyunsaturated fatty acids mediate pain associated with tissue injury and inflammation.

PubMed

Shapiro, Haim; Singer, Pierre; Ariel, Amiram

2016-08-01

Pain is a complex sensation that may be protective or cause undue suffering and loss of function, depending on the circumstances. Peripheral nociceptor neurons (PNs) innervate most tissues, and express ion channels, nocisensors, which depolarize the cell in response to intense stimuli and numerous substances. Inflamed tissues manifest inflammatory hyperalgesia in which the threshold for pain and the response to painful stimuli are decreased and increased, respectively. Constituents of the inflammatory milieu sensitize PNs, thereby contributing to hyperalgesia. Polyunsaturated fatty acids undergo enzymatic and free radical-mediated oxygenation into an array of bioactive metabolites, oxygenated polyunsaturated fatty acids (oxy-PUFAs), including the classic eicosanoids. Oxy-PUFA production is enhanced during inflammation. Pioneering studies by Vane and colleagues from the early 1970s first implicated classic eicosanoids in the pain associated with inflammation. Here, we review the production and action of oxy-PUFAs that are not classic eicosanoids, but nevertheless are produced in injured/ inflamed tissues and activate or sensitize PNs. In general, oxy-PUFAs that sensitize PNs may do so directly, by activation of nocisensors, ion channels or GPCRs expressed on the surface of PNs, or indirectly, by increasing the production of inflammatory mediators that activate or sensitize PNs. We focus on oxy-PUFAs that act directly on PNs. Specifically, we discuss the role of arachidonic acid-derived 12S-HpETE, HNE, ONE, PGA2, iso-PGA2 and 15d-PGJ2, 5,6-and 8,9-EET, PGE2-G and 8R,15S-diHETE, as well as the linoleic acid-derived 9-and 13-HODE in inducing acute nocifensive behavior and/or inflammatory hyperalgesia in rodents. The nocisensors TRPV1, TRPV4 and TRPA1, and putative Gαs-type GPCRs are the PN targets of these oxy-PUFAs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Function and the patient with chronic low back pain.

PubMed

Strong, J; Ashton, R; Large, R G

1994-09-01

To undertake a comparative examination of the reliability and validity of two frequently used self-report measures of functional disability, the Pain Disability Index (PDI) and the Oswestry Low Back Pain Disability Questionnaire (OLBPDQ). A descriptive ex-post facto design was used in the study. Pain clinics and neurosurgical units at three metropolitan hospitals. One hundred patients with chronic low back pain of noncancer origin were administered the two questionnaires as part of a larger questionnaire battery. Acceptable internal consistency values of 0.76 for the PDI and 0.71 for the OLBPDQ were obtained. A correlation of r = 0.63 was found between the PDI and the OLBPDQ, supporting the concurrent validity of the two scales. Both the scales were found to be correlated to the Beck Depression Inventory scores (PDI, r = 0.42; OLBPDQ, r = 0.39), with higher disability associated with greater depression. Only the total PDI score was found to be sensitive to functional status differences within the patient sample. These findings support other recent work in favor of the PDI. The PDI had a slightly higher internal consistency and was more sensitive than the OLBPDQ.

Childhood Adversity and Pain Sensitization.

PubMed

You, Dokyoung Sophia; Meagher, Mary W

Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

A soft patellar tendon on ultrasound elastography is associated with pain and functional deficit in volleyball players.

PubMed

Ooi, Chin Chin; Richards, Paula J; Maffulli, Nicola; Ede, David; Schneider, Michal E; Connell, David; Morrissey, Dylan; Malliaras, Peter

2016-05-01

To investigate the diagnostic performance of grey scale Ultrasound (US), power Doppler (PD) and US elastography for diagnosing painful patellar tendinopathy, and to establish their relationship with Victorian Institute of Sport Assessment-Patella (VISA-P) scores in a group of volleyball players with and without symptoms of patellar tendinopathy. Cross-sectional study. Thirty-five volleyball players (70 patellar tendons) were recruited during a national university volleyball competition. Players were imaged with conventional US followed by elastography. The clinical findings of painful patellar tendons were used as the reference standard for diagnosing patellar tendinopathy. In addition, all participants completed the VISA-P questionnaires. Of the 70 patellar tendons, 40 (57.1%) were clinically painful. The diagnostic accuracy of grey scale US, PD and elastography were 60%, 50%, 62.9%, respectively, with sensitivity/specificity of 72.5%/43.3%, 12.5%/100%, and 70%/53.3%, respectively. Combined US elastography and grey scale imaging achieved 82.5% sensitivity, 33.3% specificity and 61.4% accuracy while routine combination technique of PD and grey scale imaging revealed 72.5% sensitivity, 43.3% specificity and 60.0% accuracy. Tendons in players categorized as soft on elastography had statistically significantly greater AP thickness (p<0.001) and lower VISA-P scores (p=0.004) than those categorized as hard. There was no significant association between grey scale US abnormalities (hypoechogenicities and/or fusiform swelling) and VISA-P scores (p=0.098). Soft tendon properties depicted by US elastography may be more related to patellar tendon symptoms compared to grey scale US abnormalities. The supplementation of US elastography to conventional US may enhance the sensitivity for diagnosing patellar tendinopathy in routine clinical practice. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Neuropathic Pain and Psychological Morbidity in Patients with Treated Leprosy: A Cross-Sectional Prevalence Study in Mumbai

PubMed Central

Lasry-Levy, Estrella; Hietaharju, Aki; Pai, Vivek; Ganapati, Ramaswamy; Rice, Andrew S. C.; Haanpää, Maija; Lockwood, Diana N. J.

2011-01-01

Background Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated. Methodology/Principal Findings Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity. Conclusions/Significance One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity. PMID:21408111

Wallet Neuritis - An Example of Peripheral Sensitization.

PubMed

Siddiq, Md Abu Bakar; Jahan, Israt; Masihuzzaman, Sam

2017-03-09

Wallet neuritis is an example of extra-spinal tunnel neuropathy concerning sciatic nerve. Its clinical appearance often gets confused with sciatica of lumbar spine origin. Wallet-induced chronic sciatic nerve constriction produces gluteal and ipsilateral lower extremity pain, tingling, and burning sensation. It was Lutz, first describing credit-card wallet sciatica in an Attorney, surfaced on Journal of American Medical Association (JAMA), 1978; however, the condition has not been well-studied in various other occupations. In this write-up, I take the privilege of demonstrating wallet neuritis as an example of peripheral sensitization in three different professionals namely specialist doctor, driver, and banker first time in Bangladesh. All the three patients demonstrated about aggravated gluteal pain with radiation on the ipsilateral lower extremity while remained seated on heavy wallet for a while, fortunately improved discontinuing such stuff with. Alongside, radical wallectomy, piriformis stretching exercise on the affected side had also been recommended and found worthy in terms of pain relief. long-standing use of rear pocket wallet may compress and sensitize ipsilateral sciatic nerve, generating features resembling lumbago sciatica; thereby, remains a source of patients' misery and diagnostic illusion for pain physicians as well. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development and validation of the French-Canadian Chronic Pain Self-efficacy Scale

PubMed Central

Lacasse, Anaïs; Bourgault, Patricia; Tousignant-Laflamme, Yannick; Courtemanche-Harel, Roxanne; Choinière, Manon

2015-01-01

BACKGROUND: Perceived self-efficacy is a non-negligible outcome when measuring the impact of self-management interventions for chronic pain patients. However, no validated, chronic pain-specific self-efficacy scales exist for studies conducted with French-speaking populations. OBJECTIVES: To establish the validity of the use of the French-Canadian Chronic Pain Self-efficacy Scale (FC-CPSES) among chronic pain patients. METHODS: The Chronic Disease Self-Efficacy Scale is a validated 33-item self-administered questionnaire that measures perceived self-efficacy to perform self-management behaviours, manage chronic disease in general and achieve outcomes (a six-item version is also available). This scale was adapted to the context of chronic pain patients following cross-cultural adaptation guidelines. The FC-CPSES was administered to 109 fibromyalgia and 34 chronic low back pain patients (n=143) who participated in an evidence-based self-management intervention (the PASSAGE program) offered in 10 health care centres across the province of Quebec. Cronbach’s alpha coefficients (α) were calculated to determine the internal consistency of the 33- and six-item versions of the FC-CPSES. With regard to convergent construct validity, the association between the FC-CPSES baseline scores and related clinical outcomes was examined. With regard to the scale’s sensitivity to change, pre- and postintervention FC-CPSES scores were compared. RESULTS: Internal consistency was high for both versions of the FC-CPSES (α=0.86 to α=0.96). Higher self-efficacy was significantly associated with higher mental health-related quality of life and lower pain intensity and catastrophizing (P<0.05), supporting convergent validity of the scale. There was a statistically significant increase in FC-CPSES scores between pre- and postintervention measures for both versions of the FC-CPSES (P<0.003), which supports their sensitivity to clinical change during an intervention. CONCLUSIONS: These data suggest that both versions of the FC-CPSES are reliable and valid for the measurement of pain management self-efficacy among chronic pain patients. PMID:25848845

Cold Pressor Pain Sensitivity in Twins Discordant for Chronic Fatigue Syndrome

PubMed Central

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

2010-01-01

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

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

PubMed Central

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

2009-01-01

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

Emotional modulation of pain and spinal nociception in fibromyalgia.

PubMed

Rhudy, Jamie L; DelVentura, Jennifer L; Terry, Ellen L; Bartley, Emily J; Olech, Ewa; Palit, Shreela; Kerr, Kara L

2013-07-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (eg, depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in 4 blocks; 2 blocks assessed only physiological-emotional reactions (ie, pleasure/arousal ratings, corrugator electromyography, startle modulation, skin conductance) in the absence of pain, and 2 blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (eg, reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all 3 groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2017-04-01

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

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

PubMed

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

2010-08-01

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

Granulocyte-colony–stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis

PubMed Central

Basso, Lilian; Lapointe, Tamia K.; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D.; Kurrasch, Deborah M.; Altier, Christophe

2017-01-01

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony–stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF–induced visceral pain in vivo. Finally, administration of G-CSF–neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron–microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain. PMID:28973941

Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

PubMed

Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

2017-10-17

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

Pain Reduces Sexual Motivation in Female But Not Male Mice

PubMed Central

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

2014-01-01

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

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

PubMed Central

Goodin, Burel R.; Bulls, Hailey W.

2014-01-01

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

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

PubMed

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

2008-11-15

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

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

PubMed

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

2015-02-01

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

Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.

PubMed

Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef

2014-09-01

Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (P<0.001). Tramadol increased the PWT by 336% in CCI rats (P<0.001) and by 16% in sham (P<0.05). On the EPM, CCI rats spent 45% less time than sham on the open arms of the maze (P<0.05). Tramadol increased the time spent on the open arms of CCI rats by 67% (P<0.05) and had no significant effect on sham. During the FST, CCI rats showed 28% longer immobility than sham (P<0.01). Tramadol reduced the immobility time in CCI rats by 22% (P<0.001), while having no effect on sham. Tramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2010-01-01

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

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

PubMed

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

2012-01-01

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

Psychosocial factors partially mediate the relationship between mechanical hyperalgesia and self-reported pain.

PubMed

Mason, Kayleigh J; O'Neill, Terence W; Lunt, Mark; Jones, Anthony K P; McBeth, John

2018-01-26

Amplification of sensory signalling within the nervous system along with psychosocial factors contributes to the variation and severity of knee pain. Quantitative sensory testing (QST) is a non-invasive test battery that assesses sensory perception of thermal, pressure, mechanical and vibration stimuli used in the assessment of pain. Psychosocial factors also have an important role in explaining the occurrence of pain. The aim was to determine whether QST measures were associated with self-reported pain, and whether those associations were mediated by psychosocial factors. Participants with knee pain identified from a population-based cohort completed a tender point count and a reduced QST battery of thermal, mechanical and pressure pain thresholds, temporal summation, mechanical pain sensitivity (MPS), dynamic mechanical allodynia (DMA) and vibration detection threshold performed following the protocol by the German Research Network on Neuropathic Pain. QST assessments were performed at the most painful knee and opposite forearm (if pain-free). Participants were asked to score for their global and knee pain intensities within the past month (range 0-10), and complete questionnaire items investigating anxiety, depression, illness perceptions, pain catastrophising, and physical functioning. QST measures (independent variable) significantly correlated (Spearman's rho) with self-reported pain intensity (dependent variable) were included in structural equation models with psychosocial factors (latent mediators). Seventy-two participants were recruited with 61 participants (36 women; median age 64 years) with complete data included in subsequent analyses. Tender point count was significantly correlated with global pain intensity. DMA at the knee and MPS at the most painful knee and opposite pain-free forearm were significantly correlated with both global pain and knee pain intensities. Psychosocial factors including pain catastrophising sub-scales (rumination and helplessness) and illness perceptions (consequences and concern) were significant partial mediators of the association with global pain intensity when loaded on to a latent mediator for: tender point count [75% total effect; 95% confidence interval (CI) 22%, 100%]; MPS at the knee (49%; 12%, 86%); and DMA at the knee (63%; 5%, 100%). Latent psychosocial factors were also significant partial mediators of the association between pain intensity at the tested knee with MPS at the knee (30%; 2%, 58%), but not for DMA at the knee. Measures of mechanical hyperalgesia at the most painful knee and pain-free opposite forearm were associated with increased knee and global pain indicative of altered central processing. Psychosocial factors were significant partial mediators, highlighting the importance of the central integration of emotional processing in pain perception. Associations between mechanical hyperalgesia at the forearm and knee, psychosocial factors and increased levels of clinical global and knee pain intensity provide evidence of altered central processing as a key mechanism in knee pain, with psychological factors playing a key role in the expression of clinical pain.

Persistent arm pain is distinct from persistent breast pain following breast cancer surgery.

PubMed

Langford, Dale J; Paul, Steven M; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D; Hamolsky, Deborah; Luce, Judith A; Kober, Kord M; Neuhaus, John M; Cooper, Bruce A; Aouizerat, Bradley E; Miaskowski, Christine

2014-12-01

Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2013-09-01

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

Immediate Changes Following Manual Therapy in Resting State Functional Connectivity As Measured By Magnetic Resonance Imaging (fMRI) In Subjects With Induced Low Back Pain

PubMed Central

Gay, Charles W.; Robinson, Michael E.; George, Steven Z.; Perlstein, William M.; Bishop, Mark D.

2014-01-01

Objective The purpose of this study was to use functional magnetic resonance imaging (fMRI) to investigate the immediate changes in functional connectivity (FC) between brain regions that process and modulate the pain experience following 3 different types of manual therapies (MT) and to identify reductions in experimentally induced myalgia and changes in local and remote pressure pain sensitivity. Methods Twenty-four participants (17 females, mean age ± SD = 21.6 ± 4.2 years), who completed an exercise-injury protocol to induce low back pain, were randomized into 3 groups: chiropractic spinal manipulation (n=6), spinal mobilization (n=8) or therapeutic touch (n=10). The primary outcome was the immediate change in FC as measured on fMRI between the following brain regions: somatosensory cortex, secondary somatosensory cortex, thalamus, anterior and posterior cingulate cortices, anterior and poster insula, and periaqueductal grey. Secondary outcomes were immediate changes in pain intensity measured with a 101-point numeric rating scale, and pain sensitivity, measured with a hand-held dynamometer. Repeated measures ANOVA models and correlation analyses were conducted to examine treatment effects and the relationship between within-person changes across outcome measures. Results Changes in FC were found between several brain regions that were common to all 3 manual therapy interventions. Treatment-dependent changes in FC were also observed between several brain regions. Improvement was seen in pain intensity following all interventions (p<0.05) with no difference between groups (p>0.05). There were no observed changes in pain sensitivity, or an association between primary and secondary outcome measures. Conclusion These results suggest that manual therapies (chiropractic spinal manipulation, spinal mobilization, and therapeutic touch) have an immediate effect on the FC between brain regions involved in processing and modulating the pain experience. This suggests that neurophysiological changes following MT may be an underlying mechanism of pain relief. PMID:25284739

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

PubMed

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

2012-06-01

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

Sensitivity and specificity of the Manchester Triage System in risk prioritization of patients with acute myocardial infarction who present with chest pain.

PubMed

Nishi, Fernanda A; Polak, Catarina; Cruz, Diná de Almeida Lopes Monteiro da

2018-05-01

The purpose of the Manchester Triage System is to clinically prioritize each patient seeking care in an emergency department. Patients with suspected acute myocardial infarction who have typical symptoms including chest pain should be classified in the highest priority groups, requiring immediate medical assistance or care within 10 min. As such, the Manchester Triage System should present adequate sensitivity and specificity. This study estimated the sensitivity and specificity of the Manchester Triage System in the triage of patients with chest pain related to the diagnosis of acute myocardial infarction, and the associations between the performance of the Manchester Triage System and selected variables. This was an observational, analytical, cross-sectional, retrospective study. The sensitivity and specificity of the Manchester Triage System were estimated by verifying the triage classification received by these patients and their established medical diagnoses. The sample was composed of 10,087 triage episodes, in which 139 (1.38%) patients had a diagnosis of acute myocardial infarction. In 49 episodes, confirmation of medical diagnosis was not possible. The estimated sensitivity of the Manchester Triage System was 44.60% (36.18-53.27%) and the estimated specificity was 91.30% (90.73-91.85%). Of the 10,038 episodes in which the diagnosis of acute myocardial infarction was confirmed or excluded, 938 patients (9.34%) received an incorrect classification - undertriage or overtriage. This study showed that the specificity of the Manchester Triage System was very good. However, the low sensitivity based on the Manchester Triage System indicated that patients in high priority categories were undertriaged, leading to longer wait times and associated increased risks of adverse events.

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

PubMed

Defrin, Ruth; Eli, Ilana; Pud, Dorit

2011-06-01

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

Musculoskeletal Pain, Self-reported Physical Function, and Quality of Life in the Teen–Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Cohort

PubMed Central

Bout-Tabaku, Sharon; Michalsky, Marc P.; Jenkins, Todd M.; Baughcum, Amy; Zeller, Meg H.; Brandt, Mary L.; Courcoulas, Anita; Buncher, Ralph; Helmrath, Michael; Harmon, Carroll M.; Chen, Mike K.; Inge, Thomas H.

2015-01-01

IMPORTANCE Obesity is associated with chronic musculoskeletal pain and is a risk factor for disability and osteoarthritis. OBJECTIVES To describe the prevalence, sites, and intensity of musculoskeletal pain in adolescents with severe obesity; to evaluate associations between musculoskeletal pain and self-reported physical function as well as weight-related quality of life; and to evaluate the association between musculoskeletal pain and high-sensitivity C-reactive protein level. DESIGN, SETTING, AND PARTICIPANTS Teen–Longitudinal Assessment of Bariatric Surgery (Teen-LABS) is a prospective, observational study that collects standardized data on adolescents undergoing weight loss surgery at 5 US centers. We examined baseline data from this cohort between February 28, 2007, and December 30, 2011. We excluded adolescents with Blount disease and slipped capital femoral epiphyses. A total of 233 participants were included in these analyses. MAIN OUTCOMES AND MEASURES We assessed musculoskeletal pain and pain intensity of the lower back, hips, knees, and ankles/feet using the visual analog scale, categorizing musculoskeletal pain into lower back pain, lower extremity (hips, knees, and feet/ankles combined) pain, and no pain. We assessed self-reported physical function status with the Health Assessment Questionnaire Disability Index and assessed weight-related quality of life with the Impact of Weight on Quality of Life–Kids measure. We adjusted for sex, race, age at surgery, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and clinical depressive symptoms in regression analyses. RESULTS Among the 233 participants, the mean (SD) age at surgery was 17.1 (1.56) years and the median BMI was 50.4. Participants were predominantly female (77%), white (73%), and non-Hispanic (93%). Among the participants, 49% had poor functional status and 76% had musculoskeletal pain. Lower back pain was prevalent (63%), followed by ankle/foot (53%), knee (49%), and hip (31%) pain; 26% had pain at all 4 sites. In adjusted analyses, compared with pain-free participants, those reporting lower extremity pain had greater odds of having poor physical function according to scores on the Health Assessment Questionnaire Disability Index (odds ratio = 2.82; 95% CI, 1.35 to 5.88; P < .01). Compared with pain-free participants, those reporting lower extremity pain had significantly lower Impact of Weight on Quality of Life–Kids total scores (β = −9.42; 95% CI, −14.15 to −4.69; P < .01) and physical comfort scores (β = −17.29; 95% CI, −23.32 to −11.25; P < .01). After adjustment, no significant relationship was observed between musculoskeletal pain and high-sensitivity C-reactive protein level. CONCLUSIONS AND RELEVANCE Adolescents with severe obesity have musculoskeletal pain that limits their physical function and quality of life. Longitudinal follow-up will reveal whether weight loss surgery reverses pain and physical functional limitations and improves quality of life. PMID:25915190

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

PubMed

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

2009-12-15

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

Tonic blood pressure modulates the relationship between baroreceptor cardiac reflex sensitivity and cognitive performance.

PubMed

Del Paso, Gustavo A Reyes; González, M Isabel; Hernández, José Antonio; Duschek, Stefan; Gutiérrez, Nicolás

2009-09-01

This study explored the effects of tonic blood pressure on the association between baroreceptor cardiac reflex sensitivity and cognitive performance. Sixty female participants completed a mental arithmetic task. Baroreceptor reflex sensitivity was assessed using sequence analysis. An interaction was found, indicating that the relationship between baroreceptor reflex sensitivity and cognitive performance is modulated by blood pressure levels. Reflex sensitivity was inversely associated to performance indices in the subgroup of participants with systolic blood pressure above the mean, whereas the association was positive in participants with systolic values below the mean. These results are in accordance with the findings in the field of pain perception and suggest that tonic blood pressure modulates the inhibitory effects of baroreceptor stimulation on high central nervous functions.

PERSISTENT ARM PAIN IS DISTINCT FROM PERSISTENT BREAST PAIN FOLLOWING BREAST CANCER SURGERY

PubMed Central

Langford, Dale J.; Paul, Steven M.; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D.; Hamolsky, Deborah; Luce, Judith A.; Kober, Kord M.; Neuhaus, John M.; Cooper, Bruce A.; Aouizerat, Bradley E.; Miaskowski, Christine

2014-01-01

Persistent pain following breast cancer surgery is well-documented. However, it is not well characterized in terms of the anatomic site effected (i.e., breast, arm). In two separate growth mixture modeling analyses, we identified subgroups of women (n=398) with distinct breast pain and arm pain trajectories. Based on the fact that these latent classes differed by anatomic site, types if tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. Purposes of this companion study were to identify demographic and clinical characteristics that differed between the two arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection (ALND) sites, pain qualities, pain interference, and hand and arm function; as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the Moderate Arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and ALND site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. Perspective: For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. PMID:25439319

Perceived racial discrimination, but not mistrust of medical researchers, predicts the heat pain tolerance of African Americans with symptomatic knee osteoarthritis

PubMed Central

Pham, Quyen T.; Glover, Toni L.; Sotolongo, Adriana; King, Christopher D.; Sibille, Kimberly T.; Herbert, Matthew S.; Cruz-Almeida, Yenisel; Sanden, Shelley H.; Staud, Roland; Redden, David T.; Bradley, Laurence A.; Fillingim, Roger B.

2014-01-01

Objective Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans. It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli, which, in turn, could influence clinical pain severity. This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic whites. Mistrust of medical researchers was also assessed given its potential to affect responses to the noxious stimuli. Method One hundred and thirty (52% African American, 48% non-Hispanic white) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions. In session one, individuals provided demographic, socioeconomic, physical and mental health information. They completed questionnaires related to perceived lifetime frequency of racial discrimination and mistrust of medical researchers. In session two, individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity, particularly heat pain tolerance. Results African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical researchers compared to non-Hispanic whites. Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic whites. Mistrust of medical researchers did not significantly predict heat pain tolerance for either racial group Conclusion These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli. PMID:24219416

Differential dopamine function in fibromyalgia.

PubMed

Albrecht, Daniel S; MacKie, Palmer J; Kareken, David A; Hutchins, Gary D; Chumin, Evgeny J; Christian, Bradley T; Yoder, Karmen K

2016-09-01

Approximately 30 % of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [(18)F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and 11 female controls completed study procedures. Subjects received one FAL PET scan while performing a "2-back" task, and one while performing a "0-back" (attentional control, "baseline") task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.

Detection of osteophytes and subchondral cysts in the knee with use of tomosynthesis.

PubMed

Hayashi, Daichi; Xu, Li; Roemer, Frank W; Hunter, David J; Li, Ling; Katur, Avinash M; Guermazi, Ali

2012-04-01

To evaluate the diagnostic performance of tomosynthesis in depicting osteophytes and subchondral cysts, with use of magnetic resonance (MR) imaging as the reference, and to test whether the lesions detected at radiography and tomosynthesis are associated with pain. The study was approved by local institutional review board, and all subjects gave written informed consent. Forty subjects (80 knees) older than 40 years were recruited irrespective of knee pain or radiographic osteoarthritis. Knees were imaged with radiography, tomosynthesis, and MR imaging. Presence of osteophytes and subchondral cysts in four locations of tibiofemoral joint (medial and lateral femur and tibia) was recorded. Knee pain was assessed by using the Western Ontario and McMaster University pain subscale. MR imaging depicted 171 osteophytes and 51 subchondral cysts. Tomosynthesis had a higher sensitivity for osteophyte detection in left and right lateral femur (0.96 vs 0.75, P = .025, and 1.00 vs 0.71, P = .008, respectively), right medial femur (0.94 vs 0.72, P = .046), and right lateral tibia (1.00 vs 0.83, P = .046). For subchondral cyst detection, the sensitivity of tomosynthesis was 0.14-1.00 and that of radiography was 0.00-0.56. Both modalities had similar specificity for both lesions. Subjects with tomosynthesis-depicted osteophytes (odds ratio, 4.2-6.4; P = .001-.011) and medially located subchondral cysts (odds ratio, 6.7-17.8; P = .004-.03) were more likely to feel pain than those without. However, radiography-depicted osteophytes were more strongly associated with pain than were tomosynthesis-depicted osteophytes. Tomosynthesis depicted more osteophytes and subchondral cysts than did radiography. Subjects with tomosynthesis-depicted osteophytes and subchondral cysts were more likely to feel pain than those without such lesions. © RSNA, 2012.

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

PubMed

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

2014-03-01

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

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

PubMed Central

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

2005-01-01

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

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

PubMed

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

2016-08-31

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2011-01-01

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

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.

Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

PubMed Central

Kannampalli, Pradeep; Sengupta, Jyoti N

2015-01-01

Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life. Despite years of extensive research and the availability of several therapeutic options, management of patients with chronic visceral pain is often inadequate, resulting in frustration for both patients and physicians. This is, most likely, because the mechanisms associated with chronic visceral pain are different from those of acute pain. Accumulating evidence from years of research implicates several receptors and ion channels in the induction and maintenance of central and peripheral sensitization during chronic pain states. Understanding the specific role of these receptors will facilitate to capitalize on their unique properties to augment the therapeutic efficacy while at the same time minimizing unwanted side effects. The aim of this review is to provide a concise review of the recent literature that reports on the role of principal ionotropic receptors and metabotropic receptors in the modulation visceral pain. We also include an overview of the possibility of these receptors as potential new targets for the treatment of chronic visceral pain conditions. PMID:25843070

Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.

PubMed

Bedi, Supinder S; Yang, Qing; Crook, Robyn J; Du, Junhui; Wu, Zizhen; Fishman, Harvey M; Grill, Raymond J; Carlton, Susan M; Walters, Edgar T

2010-11-03

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury 3 d to 8 months earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared with untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 months. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C- and Aδ-fibers revealed SCI-induced SA generated in or near the somata of the neurons in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.

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

PubMed Central

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

2014-01-01

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

Experimental Pain and Opioid Analgesia in Volunteers at High Risk for Obstructive Sleep Apnea

PubMed Central

Doufas, Anthony G.; Tian, Lu; Padrez, Kevin A.; Suwanprathes, Puntarica; Cardell, James A.; Maecker, Holden T.; Panousis, Periklis

2013-01-01

Background Obstructive sleep apnea (OSA) is characterized by recurrent nocturnal hypoxia and sleep disruption. Sleep fragmentation caused hyperalgesia in volunteers, while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA. This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA. Methods After approval from the Intitutional Review Board and informed consent, we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography (PSG). Three pro-inflammatory and 3 hypoxia markers were determined in the serum. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 µg/ml), an μ-opioid agonist. Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [wake after sleep onset, number of sleep stage shifts, and lowest oxyhemoglobin saturation (SaO2) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil. Results Forty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO2 and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO2, P = 0.0440; IGFBP-1, P = 0.0013). Other pro-inflammatory mediators like interleukin-1β and tumor necrosis factor-α (TNF-α) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1β, P = 0.0218; TNF-α, P = 0.0276). Conclusions Nocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia. A serum hypoxia marker (IGFBP-1) was associated with hypoalgesia and increased potency to opioid analgesia; other pro-inflammatory mediators also predicted an enhanced opioid potency. Trial Registration: ClinicalTrials.gov NCT00672737. PMID:23382975

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

PubMed Central

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

2013-01-01

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

Nursing ward managers' perceptions of pain prevalence at the aged-care facilities in Japan: a nationwide survey.

PubMed

Takai, Yukari; Yamamoto-Mitani, Noriko; Fukahori, Hiroki; Kobayashi, Sayuri; Chiba, Yumi

2013-09-01

This study aimed to examine nursing ward managers' perceptions of pain prevalence among older residents and the strategies of pain management at the Health Service Facilities for the Elderly Requiring Care (HSFERC) in Japan and to investigate the factors related to the prevalence. Nursing ward managers in 3,644 HSFERC were asked to participate in this study. Questionnaires were sent to them regarding pain prevalence among the older residents in their wards, their provisions for pain care, and other pain management strategies. The perceived pain prevalence factors were examined statistically. The final sample comprised 439 participants (12.0%). A total of 5,219 residents (22.3%) were recognized as suffering from pain on the investigation day. Only 8 wards (1.8%) used pain management guidelines or care manuals, and 14 (3.2%) used a standardized pain scale. The ward managers' age (p = .008) and nursing experience (p = .006) showed a significant negative association with pain prevalence estimation. Moreover, there was a significant association between the groups' pain prevalence estimation and the nursing managers' beliefs that older adults were less sensitive to pain (p = .01), that pain was common among older people (p = .007), and that the time to treat residents' pain was insufficient (p = .001). The ward managers' perceptions regarding pain prevalence varied; the perceived pain rates were possibly lower than the actual percentages. Insufficient pain management strategies at the HSFERC were also suggested. An appropriate pain management strategy for Japanese aged care and its dissemination are urgently required. Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

An experimental study of pain upon stimulation of the nasal and sinus cavities.

PubMed

Clerico, Dean M

2014-01-01

To map different areas of pain sensitivity and to determine the existence and/or pattern of referred pain from upon stimulating the sinonasal cavity. Experimental human study. Mechanical and electrical stimulations to various anatomical structures and areas of the nasal and sinus cavities were conducted on nine volunteers. Intensity, location and character of pain were recorded in all subjects. The postero-superior (cephalic) aspect of the nasal cavity, primarily the anterior face of the sphenoid sinus and the superior turbinate, were the most sensitive sites, and the antero-inferior (caudal) region was the least sensitive. Referred pain to the head and face was reported by several subjects. Topographical differences in pain sensitivity exist in the sinonasal cavity. The phenomenon of referred pain from the nasal cavity was demonstrated. Copyright © 2014 Elsevier Inc. All rights reserved.

Paraspinous Lidocaine Injection for Chronic Nonspecific Low Back Pain: A Randomized Controlled Clinical Trial.

PubMed

Imamura, Marta; Imamura, Satiko Tomikawa; Targino, Rosa Alves; Morales-Quezada, León; Onoda Tomikawa, Luis C; Onoda Tomikawa, Luis G; Alfieri, Fabio M; Filippo, Thais R; da Rocha, Ivan D; Neto, Raul Bolliger; Fregni, Felipe; Battistella, Linamara Rizzo

2016-05-01

In this large, sham-controlled, randomized trial, we examined the efficacy of the combination of standard treatment and paraspinous lidocaine injection compared with standard therapy alone in subjects with chronic low back pain. There is little research-based evidence for the routine clinical use of paraspinous lidocaine injection for low back pain. A total of 378 subjects with nonspecific chronic low back pain were randomized to 3 groups: paraspinous lidocaine injection, analgesics, and exercises (group 1, LID-INJ); sham paraspinous lidocaine injection, analgesics, and exercises (group 2, SH-INJ); and analgesics and exercises (group 3, STD-TTR). A blinded rater assessed the study outcomes at 3 time points: baseline, after treatment, and after 3 months of follow-up. There were increased frequency of pain responses and better low back functional scores in the LID-INJ group compared with the SH-INJ and STD-TTR groups. These effects remained at the 3-month follow-up but differed between all 3 groups. There were significant changes in pain threshold immediately after treatment, supporting the effects of this intervention in reducing central sensitization. Paraspinous lidocaine injection therapy is not associated with a higher risk of adverse effects compared with conventional treatment and sham injection. Its effects on hyperalgesia might correlate with changes in central sensitization. NCT02387567. There are few data to support paraspinous lidocaine injection use in patients with nonspecific chronic low back pain. Our results show that this therapy when combined with standard therapy significantly increases the number of responders versus standard treatment alone. Its effects on hyperalgesia might correlate with a change in central sensitization. Copyright © 2016. Published by Elsevier Inc.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2014-08-01

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

The anti-nociceptive agent ralfinamide inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ currents in dorsal root ganglion neurons.

PubMed

Stummann, Tina C; Salvati, Patricia; Fariello, Ruggero G; Faravelli, Laura

2005-03-14

Tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ channels contribute to the abnormal spontaneous firing in dorsal root ganglion neurons associated with neuropathic pain. Effects of the anti-nociceptive agent ralfinamide on tetrodotoxin-resistant and tetrodotoxin-sensitive currents in rat dorsal root ganglion neurons were therefore investigated by patch clamp experiments. Ralfinamide inhibition was voltage-dependent showing highest potency towards inactivated channels. IC50 values for tonic block of half-maximal inactivated tetrodotoxin-resistant and tetrodotoxin-sensitive currents were 10 microM and 22 microM. Carbamazepine, an anticonvulsant used in the treatment of pain, showed significantly lower potency. Ralfinamide produced a hyperpolarising shift in the steady-state inactivation curves of both currents confirming the preferential interaction with inactivated channels. Additionally, ralfinamide use and frequency dependently inhibited both currents and significantly delayed repriming from inactivation. All effects were more pronounced for tetrodotoxin-resistant than tetrodotoxin-sensitive currents. The potency and mechanisms of actions of ralfinamide provide a hypothesis for the anti-nociceptive properties found in animal models.

Anorectal and Pelvic Pain.

PubMed

Bharucha, Adil E; Lee, Tae Hee

2016-10-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans

PubMed Central

Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

2009-01-01

Background There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression. Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions. PMID:19570226

Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans.

PubMed

Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

2009-07-01

There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on micro-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression. This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.

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

PubMed Central

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

2012-01-01

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

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins

PubMed Central

TIAN, JINGE; YU, TINGTING; XU, YONGMING; PU, SHAOFENG; LV, YINGYING; ZHANG, XIN; DU, DONGPING

2018-01-01

ABSTRACT Introduction Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. Methods We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. Results TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Conclusions Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT. PMID:28846565

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins.

PubMed

Tian, Jinge; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Lv, Yingying; Zhang, Xin; DU, Dongping

2018-01-01

Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT.

Emotional modulation of pain and spinal nociception in fibromyalgia

PubMed Central

Rhudy, Jamie L.; DelVentura, Jennifer L.; Terry, Ellen L.; Bartley, Emily J.; Olech, Ewa; Palit, Shreela; Kerr, Kara L.

2013-01-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (e.g., depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in four blocks; two blocks assessed only physiological-emotional reactions (i.e., pleasure/arousal ratings, corrugator EMG, startle modulation, skin conductance) in the absence of pain and two blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (e.g., reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all three groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. PMID:23622762

Early Postoperative Magnetic Resonance Imaging in Detecting Radicular Pain After Lumbar Decompression Surgery: Retrospective Study of the Relationship Between Dural Sac Cross-sectional Area and Postoperative Radicular Pain.

PubMed

Futatsugi, Toshimasa; Takahashi, Jun; Oba, Hiroki; Ikegami, Shota; Mogami, Yuji; Shibata, Syunichi; Ohji, Yoshihito; Tanikawa, Hirotaka; Kato, Hiroyuki

2017-07-01

A retrospective analysis. To evaluate the association between early postoperative dural sac cross-sectional area (DCSA) and radicular pain. The correlation between postoperative magnetic resonance imaging (MRI) findings and postoperative neurological symptoms after lumbar decompression surgery is controversial. This study included 115 patients who underwent lumbar decompression surgery followed by MRI within 7 days postoperatively. There were 46 patients with early postoperative radicular pain, regardless of whether the pain was mild or similar to that before surgery. The intervertebral level with the smallest DCSA was identified on MRI and compared preoperatively and postoperatively. Risk factors for postoperative radicular pain were determined using univariate and multivariate analyses. Subanalysis according to absence/presence of a residual suction drain also was performed. Multivariate regression analysis showed that smaller postoperative DCSA was significantly associated with early postoperative radicular pain (per -10 mm; odds ratio, 1.26). The best cutoff value for radicular pain was early postoperative DCSA of 67.7 mm. Even with a cutoff value of <70 mm, sensitivity and specificity are 74.3% and 75.0%, respectively. Early postoperative DCSA was significantly larger before suction drain removal than after (119.7±10.1 vs. 93.9±5.4 mm). Smaller DCSA in the early postoperative period was associated with radicular pain after lumbar decompression surgery. The best cutoff value for postoperative radicular pain was 67.7 mm. Absence of a suction drain at the time of early postoperative MRI was related to smaller DCSA.

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

PubMed

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

2008-02-01

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

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

PubMed

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

2018-04-01

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

Immune mediators of chronic pelvic pain syndrome

PubMed Central

Murphy, Stephen F.; Schaeffer, Anthony J.; Thumbikat, Praveen

2016-01-01

The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease. PMID:24686526

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

PubMed Central

Sturgeon, John A.; Johnson, Kevin A.

2017-01-01

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

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

PubMed

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

2017-01-01

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

Gender differences in pain: do emotions play a role?

PubMed

Rhudy, Jamie L; Williams, Amy E

2005-12-01

Research suggests that the influence of gender on the processing and experience of pain is a result of several mechanisms. One mediating variable is emotion, which may modulate pain through an interaction of valence (pleasant-unpleasant) and arousal (calm-excited). This review examines whether gender differences in the experience and processing of emotion contribute to differences in the modulation and perception of pain. An English-language search of MEDLINE and PsycINFO was conducted from 1887 to May 2005. Additional literature was obtained from reference lists of articles retained in the initial search. Emotion appears to influence pain through a valence-by-arousal interaction. Specifically, negatively valenced emotions with low to moderate arousal (eg, anxiety) enhance pain, whereas negatively valenced emotions with high arousal (eg, fear) reduce pain. In contrast, positively valenced emotions always reduce pain, as long as minimal arousal is achieved. Some evidence suggests that women are more sensitive than men to threat-related stimuli and thus experience more negative affect than men. This would generally lead to enhanced pain perception in women. It is also possible that women are more likely than men to experience negative affect with high arousal (intense fear) and thus pain inhibition. However, the relatively lower base rate of intense negative emotions is not likely to contribute much to gender differences in pain. Evidence also suggests that men may be more sensitive to positive events, particularly sexual/erotic stimuli, which may lead to more positive emotion-induced pain reduction in men, relative to women. This review suggests that gender differences in the experience of pain may arise from differences in the experience and processing of emotion that, in turn, differentially alter pain processing. Specifically, the system associated with negative affect may be more attuned to threatening stimuli in women, and the system associated with positive affect may be more attuned to pleasurable stimuli in men. However, there is a paucity of research directly addressing this issue; much of the research on this topic has failed to test a comprehensive model of emotion, failed to use adequate manipulation checks, or failed to use within-subject experimental designs that control for intra- and interindividual differences. Therefore, it is concluded that additional research is warranted.

Self-reported sleep duration associated with distraction analgesia, hyperemia, and secondary hyperalgesia in the heat-capsaicin nociceptive model.

PubMed

Campbell, Claudia M; Bounds, Sara C; Simango, Mpepera B; Witmer, Kenneth R; Campbell, James N; Edwards, Robert R; Haythornthwaite, Jennifer A; Smith, Michael T

2011-07-01

Although sleep deprivation is known to heighten pain sensitivity, the mechanisms by which sleep modifies nociception are largely unknown. Few studies of sleep-pain interactions have utilized quantitative sensory testing models that implicate specific underlying physiologic mechanisms. One possibility, which is beginning to receive attention, is that differences in sleep may alter the analgesic effects of distraction. We utilized the heat-capsaicin nociceptive model to examine whether self-reported habitual sleep duration is associated with distraction analgesia, the degree of secondary hyperalgesia and skin flare, markers implicating both central and peripheral processes that heighten pain. Twenty-eight healthy participants completed three experimental sessions in a randomized within subjects design. In the pain only condition, pain was induced for approximately 70-min via application of heat and capsaicin to the dorsum of the non-dominant hand. Verbal pain ratings were obtained at regular intervals. In the distraction condition, identical procedures were followed, but during heat-capsaicin pain, subjects played a series of video games. The third session involved assessing performance on the video games (no capsaicin). Participants indicated their normal self-reported habitual sleep duration over the past month. Individuals who slept less than 6.5 h/night in the month prior to the study experienced significantly less behavioral analgesia, increased skin flare and augmented secondary hyperalgesia. These findings suggest that reduced sleep time is associated with diminished analgesic benefits from distraction and/or individuals obtaining less sleep have a reduced ability to disengage from pain-related sensations. The secondary hyperalgesia finding may implicate central involvement, whereas enhanced skin flare response suggests that sleep duration may also impact peripheral inflammatory mechanisms. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Are there health effects of harassment in the workplace? A gender-sensitive study of the relationships between work and neck pain.

PubMed

Stock, Susan R; Tissot, France

2012-01-01

The aim of this study was to identify workplace physical and psychosocial risk factors for neck pain among male and female workers and, in particular, to study the relationship between neck pain and intimidation and sexual harassment in the workplace in a representative sample of the Quebec working population. The study sample included 5405 men and 3987 women. In multiple logistic regression analyses, when taking into account individual and other workplace factors, neck pain was significantly associated with intimidation at work among both male (odds ratio (OR) 1.4 (1.01-1.8)) and female workers (OR 1.3 (1.01-1.8)). Among female workers, neck pain was alsosignificantly associated with unwanted sexual attention (OR 1.6 (1.1-2.4)). If confirmed in prospective studies, these results suggest that interventions to prevent harassment in the workplace may help reduce musculoskeletal disorders in the workplace and that workplace programmes to reduce harassment in the workplace should include prevention of sexual harassment. While taking into account relevant personal factors and previously identified workplace physical and psychosocial risk factors, this gender-based study identifies new work exposures associated with neck pain that have not previously been studied, including unwanted sexual attention, intimidation and difficult or tense situations with the public.

Associations of varus thrust and alignment with pain in knee osteoarthritis.

PubMed

Lo, Grace H; Harvey, William F; McAlindon, Timothy E

2012-07-01

To investigate associations of varus thrust and varus static alignment with pain in patients with knee osteoarthritis (OA). This was a cross-sectional study of participants from a randomized controlled trial of vitamin D treatment for knee OA. Participants were video recorded while walking and scored for presence of varus thrust. Static alignment was measured on standard posteroanterior knee radiographs. Pain questions from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire were used to assess symptoms. We calculated means for total WOMAC pain in relation to varus thrust and static varus alignment (i.e., corrected anatomic alignment<178 degrees). Ordinal logistic regressions were performed, with responses on individual WOMAC pain questions as the outcomes and varus thrust and varus alignment as the predictors. There were 82 participants, 60% of whom were female. The mean±SD age was 65.1±8.5 years, and the mean±SD body mass index was 30.2±5.4 kg/m2. The mean total WOMAC pain score was 6.3 versus 3.9, respectively, in those with versus without definite varus thrust (P=0.007) and 5.0 versus 4.2 in those with versus without varus alignment (P=0.36). Odds ratios for pain with walking and standing were 4.7 (95% confidence interval 1.8-11.9) and 5.5 (95% confidence interval 2.2-14.2), respectively, in those with and those without definite varus thrust. There were no significant associations between varus alignment and responses to individual WOMAC pain questions. Sensitivity analyses suggested that varus classified using a more stringent definition might have been associated with pain on walking and standing. In patients with knee OA, varus thrust, and possibly varus static alignment, were associated with pain, specifically during weight-bearing activities. Treatment of varus thrust (e.g., via bracing or gait modification) may lead to improvement of symptoms. Copyright © 2012 by the American College of Rheumatology.

Clinical presentation and manual therapy for upper quadrant musculoskeletal conditions

PubMed Central

Isabel de-la-Llave-Rincón, Ana; Puentedura, Emilio J; Fernández-de-las-Peñas, César

2011-01-01

In recent years, increased knowledge of the pathogenesis of upper quadrant pain syndromes has translated to better management strategies. Recent studies have demonstrated evidence of peripheral and central sensitization mechanisms in different local pain syndromes of the upper quadrant such as idiopathic neck pain, lateral epicondylalgia, whiplash-associated disorders, shoulder impingement, and carpal tunnel syndrome. Therefore, a treatment-based classification approach where subjects receive matched interventions has been developed and, it has been found that these patients experience better outcomes than those receiving non-matched interventions. There is evidence suggesting that the cervical and thoracic spine is involved in upper quadrant pain. Spinal manipulation has been found to be effective for patients with elbow pain, neck pain, or cervicobrachial pain. Additionally, it is known that spinal manipulative therapy exerts neurophysiological effects that can activate pain modulation mechanisms. This paper exposes some manual therapies for upper quadrant pain syndromes, based on a nociceptive pain rationale for modulating central nervous system including trigger point therapy, dry needling, mobilization or manipulation, and cognitive pain approaches. PMID:23115473

Measurement Properties of the Central Sensitization Inventory: A Systematic Review.

PubMed

Scerbo, Thomas; Colasurdo, Joseph; Dunn, Sally; Unger, Jacob; Nijs, Jo; Cook, Chad

2018-04-01

Central sensitization (CS) is a phenomenon associated with several medical diagnoses, including postcancer pain, low back pain, osteoarthritis, whiplash, and fibromyalgia. CS involves an amplification of neural signaling within the central nervous system that results in pain hypersensitivity. The purpose of this systematic review was to gather published studies of a widely used outcome measure (the Central Sensitization Inventory [CSI]), determine the quality of evidence these publications reported, and examine the measurement properties of the CSI. Four databases were searched for publications from 2011 (when the CSI was developed) to July 2017. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was applied to evaluate methodological quality and risk of bias. In instances when COSMIN did not offer a scoring system for measurement properties, qualitative analyses were performed. Fourteen studies met inclusion criteria. Quality of evidence examined with the COSMIN checklist was determined to be good to excellent for all studies for their respective measurement property reports. Interpretability measures were consistent when publications were analyzed qualitatively, and construct validity was strong when examined alongside other validated measures relating to CS. An assessment of the published measurement studies of the CSI suggest the tool generates reliable and valid data that quantify the severity of several symptoms of CS. © 2017 World Institute of Pain.

Prevalence and factors associated with a higher risk of neck and back pain among permanent wheelchair users: a cross-sectional study.

PubMed

Kovacs, Francisco M; Seco, Jesús; Royuela, Ana; Barriga, Andrés; Zamora, Javier

2018-04-01

Cross-sectional study. To determine the prevalence of, and factors associated with, spinal pain among wheelchair users. Four Spanish hospitals specialized in providing care for wheelchair users. Persons who had used a wheelchair for a median (IRQ) of 10 (5;19) years, 27% of them due to reasons other than spinal cord injury, were recruited consecutively (n = 750). Data on 43 demographic, psychosocial, ergonomic, and clinical variables were collected, and analyzed. Main outcome measures were: point prevalence of neck (NP), thoracic (TP), low back pain (LBP), and pain at any spinal level (PASL); and factors associated with them. Point prevalence was 56% for NP, 54% for TP, 45% for LBP, and 76% for PSAL. PASL was associated with a lower quality of life (OR (95% CI) 0.91 (0.86; 0.97)). Multivariable regression models showed that the main factors associated with significant pain (≥1.5 VAS points) were: (a) For NP: cervical spinal injury and wheelchair seat cushion thickness, (b) For TP: thoracic spinal injury and sagittal index, (c) For LBP: thoracic or lumbar spinal injury, with some sensitivity remaining, (d) For PASL: being female, living alone, and using a non-power wheelchair. Discrimination (AUC) of these models ranged between 0.638 and 0.818. p-values in the Hosmer-Lemeshow test ranged between 0.420 and 0.701. Prevalence of spinal pain among wheelchair users is high. It is associated with a lower quality of life. Future studies should assess whether using a power wheelchair affects PASL, and if the thickness of seat cushion affects NP. Spanish Back Pain Research Network.

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

PubMed

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

2016-07-01

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

Sustained deep-tissue pain alters functional brain connectivity.

PubMed

Kim, Jieun; Loggia, Marco L; Edwards, Robert R; Wasan, Ajay D; Gollub, Randy L; Napadow, Vitaly

2013-08-01

Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2014-04-01

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

Peptidergic CGRPα primary sensory neurons encode heat and itch and tonically suppress sensitivity to cold

PubMed Central

McCoy, Eric S.; Taylor-Blake, Bonnie; Street, Sarah E.; Pribisko, Alaine L.; Zheng, Jihong; Zylka, Mark J.

2013-01-01

SUMMARY Calcitonin gene-related peptide (CGRP) is a classic molecular marker of peptidergic primary somatosensory neurons. Despite years of research, it is unknown if these neurons are required to sense pain or other sensory stimuli. Here, we found that genetic ablation of CGRPα-expressing sensory neurons reduced sensitivity to noxious heat, capsaicin and itch (histamine and chloroquine) and impaired thermoregulation but did not impair mechanosensation or β-alanine itch—stimuli associated with nonpeptidergic sensory neurons. Unexpectedly, ablation enhanced behavioral responses to cold stimuli and cold mimetics without altering peripheral nerve responses to cooling. Mechanistically, ablation reduced tonic and evoked activity in postsynaptic spinal neurons associated with TRPV1/heat, while profoundly increasing tonic and evoked activity in spinal neurons associated with TRPM8/cold. Our data reveal that CGRPα sensory neurons encode heat and itch and tonically cross-inhibit cold-responsive spinal neurons. Disruption of this crosstalk unmasks cold hypersensitivity, with mechanistic implications for neuropathic pain and temperature perception. PMID:23523592

The interfaces between vitamin D, sleep and pain.

PubMed

de Oliveira, Daniela Leite; Hirotsu, Camila; Tufik, Sergio; Andersen, Monica Levy

2017-07-01

The role of vitamin D in osteomineral metabolism is well known. Several studies have suggested its action on different biological mechanisms, such as nociceptive sensitivity and sleep-wake cycle modulation. Sleep is an important biological process regulated by different regions of the central nervous system, mainly the hypothalamus, in combination with several neurotransmitters. Pain, which can be classified as nociceptive, neuropathic and psychological, is regulated by both the central and peripheral nervous systems. In the peripheral nervous system, the immune system participates in the inflammatory process that contributes to hyperalgesia. Sleep deprivation is an important condition related to hyperalgesia, and recently it has also been associated with vitamin D. Poor sleep efficiency and sleep disorders have been shown to have an important role in hyperalgesia, and be associated with different vitamin D values. Vitamin D has been inversely correlated with painful manifestations, such as fibromyalgia and rheumatic diseases. Studies have demonstrated a possible action of vitamin D in the regulatory mechanisms of both sleep and pain. The supplementation of vitamin D associated with good sleep hygiene may have a therapeutic role, not only in sleep disorders but also in the prevention and treatment of chronic pain conditions. © 2017 Society for Endocrinology.

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

PubMed

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

2015-01-01

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

Frida Kahlo: Portrait of Chronic Pain.

PubMed

Courtney, Carol A; O'Hearn, Michael A; Franck, Carla C

2017-01-01

The Mexican artist Frida Kahlo (1907-1954) is one of the most celebrated artists of the 20th century. Although famous for her colorful self-portraits and associations with celebrities Diego Rivera and Leon Trotsky, less known is the fact that she had lifelong chronic pain. Frida Kahlo developed poliomyelitis at age 6 years, was in a horrific trolley car accident in her teens, and would eventually endure numerous failed spinal surgeries and, ultimately, limb amputation. She endured several physical, emotional, and psychological traumas in her lifetime, yet through her art, she was able to transcend a life of pain and disability. Of her work, her self-portraits are conspicuous in their capacity to convey her life experience, much of which was imbued with chronic pain. Signs and symptoms of chronic neuropathic pain and central sensitization of nociceptive pathways are evident when analyzing her paintings and medical history. This article uses a narrative approach to describe how events in the life of this artist contributed to her chronic pain. The purpose of this article is to discuss Frida Kahlo's medical history and her art from a modern pain sciences perspective, and perhaps to increase our understanding of the pain experience from the patient's perspective. © 2017 American Physical Therapy Association.

Examining the Sensitivity and Specificity of 2 Screening Instruments: Odontogenic or Temporomandibular Disorder Pain?

PubMed

Fonseca Alonso, Barbara; Nixdorf, Donald R; Shueb, Sarah S; John, Mike T; Law, Alan S; Durham, Justin

2017-01-01

Two groups of patients with orofacial pains that are clinically important to distinguish from each other are patients with odontogenic pain and temporomandibular disorder (TMD) pain. The aim of this study was to determine the sensitivity and specificity of 2 screening instruments in distinguishing between patients with these types of pain. A convenience sample of patients seeking care at an endodontic clinic and an orofacial pain clinic were recruited. The 14-item dental pain questionnaire (DePaQ) was used to screen for odontogenic pain and the 6-item TMD screener was used to screen for TMD pain. Sensitivity and specificity calculations with 95% confidence intervals (CIs) were performed for both instruments, and thresholds/acceptability/performance was assessed using published guidelines. Thirty-four patients with odontogenic pain and 37 patients with TMD pain were included in this study. The sensitivity of the DePaQ was 0.85 (95% CI, 0.69-0.95), and specificity was 0.11 (95% CI, 0.03-0.25). The sensitivity of the TMD screener was 0.92 (95% CI, 0.78-0.98), and specificity was 0.59 (95% CI, 0.41-0.75). The point estimates, a single value used to estimate the population parameter, for both the DePaQ and TMD screener were "acceptable" in identifying patients who had the pain condition in question (ie, sensitivity), whereas the point estimate for appropriately identifying patients who did not have the pain condition when they did not have it (ie, specificity) was "nonacceptable" for both. The DePaQ and the TMD screener lack diagnostic accuracy for differentiating TMD from odontogenic tooth pain without adjunctive (clinical) investigation(s) or examination. However, the TMD screener has high sensitivity for identifying true positives (ie, TMD pain) and would therefore be useful as a screening instrument when one can definitively exclude odontogenic etiology for pain on clinical and radiographic grounds, for instance in endodontic practices. In this study, the negative predictive value was also high in the TMD screener, and, therefore, we can trust a negative result (ie, when the TMD screener is negative, we can be fairly certain the pain diagnosis is not TMD and rule out TMD). Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Pain, sensory function, and neurogenic inflammatory response in young women with low mood.

PubMed

Lehoux, Cory P; Abbott, Frances V

2011-03-01

To determine the relationship of mood status to pain complaints, sensory function, neurogenic inflammatory response, and general health in young women. Ninety-three women aged 18-29 participated in the study and were categorized by SCL-90-R depression score into low-mood (n=21) and normal-mood (n=72) groups. All subjects were below the threshold for possible clinical depression. Low mood was associated with decreased tactile sensitivity, reduced response to topical capsaicin, and increased complaints of back, joint, muscle, and visceral pain, but not headache, when compared to normal mood controls. Low mood was also associated with reported poorer health and physical functioning, increased psychopathology, and family history of mood problems. These data show that even subclinical low mood is associated with marked alterations in health and psychophysiological function. Copyright © 2011 Elsevier Inc. All rights reserved.

Pain intensity, temperament traits and social support as determinants of trauma symptoms in patients suffering from rheumatoid arthritis and low-back pain.

PubMed

Rzeszutek, Marcin; Oniszczenko, Włodzimierz; Schier, Katarzyna; Biernat-Kałuża, Edyta; Gasik, Robert

2016-04-01

The main goal of our study was to investigate the relationship between age, duration of pain, pain intensity, temperament traits as postulated by the Regulative Theory of Temperament (RTT), social support dimensions and the level of trauma symptoms, as appear in post-traumatic stress disorder (PTSD) in a sample of 300 patients suffering from chronic pain in two groups comprised of 150 patients with a clinical diagnosis of rheumatoid arthritis (RA) and 150 patients with a clinical diagnosis of low-back pain (LBP). They were analyzed together as a one group of 300 patients with chronic pain. Temperament was measured with the Formal Characteristics of Behaviour - Temperament Inventory (FCB-TI). Social support was tested with the Berlin Social Support Scales (BSSS). The Numerical Rating Scale (NRS-11) was used to measure pain intensity. The level of trauma symptoms was assessed with the Post-Traumatic Stress Disorder Factorial Version Inventory (PTSDF). The results of our study suggest that the intensity of pain, participants' age, Emotional Reactivity and Sensory Sensitivity as temperament traits, need for support, and actually received social support were related to the level of trauma symptoms. The sum of the squared semi-partial correlations showed that all six variables (age, pain intensity, Emotional Reactivity, Sensory Sensitivity, need for support and actually received support), account for 20% of the variance of general trauma symptoms level. The importance of temperament traits, social support and trauma symptoms should be taken into an account in psychotherapy accompanying pharmacotherapy for pain. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

PubMed Central

Eitner, Annett; Hofmann, Gunther O.; Schaible, Hans-Georg

2017-01-01

Pain due to osteoarthritis (OA) is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF) is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate OA pain, and in some cases genetic factors influencing OA pain were found. Considering the local factors in the joint, the neuronal processes and the comorbidities, a better definition of OA pain phenotypes may become possible. Studies are under way in order to improve OA and OA pain monitoring. PMID:29163027

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2018-05-01

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

Central Sensitization Inventory as a Predictor of Worse Quality of Life Measures and Increased Length of Stay Following Spinal Fusion.

PubMed

Bennett, E Emily; Walsh, Kevin M; Thompson, Nicolas R; Krishnaney, Ajit A

2017-08-01

Central sensitization is abnormal and intense enhancement of pain mechanism by the central nervous system. Patients with central sensitization may be at higher risk of poor outcomes after spinal fusion. The Central Sensitivity Inventory (CSI) was developed to identify and quantify key symptoms related to central sensitization. In 664 patients who underwent thoracic and/or lumbar fusion, we evaluated retrospectively pretreatment CSI as a predictor of postoperative quality of life measures, length of stay, and discharge status. Preoperative Pain Disability Questionnaire scores, Patient Health Questionnaire-9 scores, and EuroQol-5 Dimensions index scores were significantly worse in patients with preoperative CSI ≥40 compared with patients with preoperative CSI <40 (P < 0.0001 for all). After adjusting for demographic variables, operation duration, and preoperative health status, preoperative CSI was significantly associated with higher postoperative Pain Disability Questionnaire total score (unadjusted P < 0.001, adjusted P = 0.009), higher postoperative Patient Health Questionnaire-9 score (unadjusted P < 0.001, adjusted P = 0.001), and lower postoperative EuroQol-5 Dimensions index (unadjusted P < 0.001, adjusted P = 0.001). For each 10-unit increase in CSI, average length of stay increased by 6.4% (95% confidence interval 0.4%-12.6%, P = 0.035). The odds of being discharged home after adjusting for confounders was not statistically related to preoperative CSI (P = 0.0709). Preoperative CSI was associated with worse quality of life outcomes and increased length of stay after spinal fusions. CSI may be an additional measure in evaluating patients preoperatively to better predict successful spinal fusion outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Low-to-Moderate Alcohol Consumption is Associated With Hippocampal Volume in Fibromyalgia and Insomnia.

PubMed

Boissoneault, Jeff; Vatthauer, Karlyn; O'Shea, Andrew; Craggs, Jason G; Robinson, Michael; Staud, Roland; Berry, Richard B; Perlstein, William; Waxenberg, Lori; McCrae, Christina S

2017-01-01

Fibromyalgia and chronic insomnia are frequently comorbid conditions with heightened sensitivity to painful stimuli, potentially subserved by the hippocampus. Recent evidence suggests moderate alcohol consumption is associated with reduced fibromyalgia symptom severity. We examined the relationship among alcohol use, hippocampal morphology, fibromyalgia, and insomnia symptom severity in 41 fibromyalgia patients (19 with insomnia). A 14-day diary of sleep, pain, and alcohol consumption was followed by structural MRI. Analyses indicated greater bilateral hippocampal volume, lower clinical pain intensity, and better sleep quality in moderate drinkers versus abstainers. Underlying mechanisms may include gamma-amino butyric acid (GABA) receptor agonism, n-methyl d-aspartate (NMDA) receptor antagonism, and psychosocial factors. Further study of the relationship between alcohol use and fibromyalgia and insomnia symptom severity is warranted.

Children's selective attention to pain and avoidance behaviour: the role of child and parental catastrophizing about pain.

PubMed

Vervoort, Tine; Trost, Zina; Van Ryckeghem, Dimitri M L

2013-10-01

The present study investigated selective attention to pain in children, its implications for child avoidance behaviour, and the moderating role of dimensions comprising child and parental catastrophizing about pain (ie, rumination, magnification, and helplessness). Participants were 59 children (31 boys) aged 10-16 years and one of their parents (41 mothers). Children performed a dot-probe task in which child facial pain displays of varying pain expressiveness were presented. Child avoidance behaviour was indexed by child pain tolerance during a cold-pressor task. Children and parents completed measures of child and parent pain catastrophizing, respectively. Findings indicated that both the nature of child selective attention to pain and the impact of selective attention upon child avoidance behaviour were differentially sensitive to specific dimensions of child and parental catastrophizing. Specifically, findings showed greater tendency to shift attention away from pain faces (i.e.,, attentional avoidance) among children reporting greater pain magnification. A similar pattern was observed in terms of parental characteristics, such that children increasingly shifted attention away from pain with increasing levels of parental rumination and helplessness. Furthermore, child attentional avoidance was associated with greater avoidance behaviour (i.e., lower pain tolerance) among children reporting high levels of pain magnification and those whose parents reported greater rumination about pain. The current findings corroborate catastrophizing as a multidimensional construct that may differentially impact outcomes and attest to the importance of assessing both child and parental characteristics in relation to child pain-related attention and avoidance behaviour. Further research directions are discussed. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement in Patients with Opioid Dependence on Methadone Maintenance Treatment.

PubMed

Dennis, B B; Bawor, M; Paul, J; Plater, C; Pare, G; Worster, A; Varenbut, M; Daiter, J; Marsh, D C; Desai, D; Thabane, L; Samaan, Z

2016-01-01

While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain. We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool. After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the ROC curve was 0.67 and the Pearson χ(2) was 37.3; (p<0.0001). The field of addiction medicine is at a lack of consensus as to the real effect of chronic pain on treatment response among opioid dependent patients. Whether it be the lack of a single "gold standard" measurement of response, or a lack of consistent measurement of pain, it is difficult to summarize and compare the results of these relatively small investigations. In comparison to the BPI, use of the simple self-reported pain has lower sensitivity for identifying patients with pain, suggesting the inconsistencies in these studies may result from differences in pain measurement. Future validation studies of pain measurement are required to address the predictive value of self-reported pain.

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

PubMed

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

2015-11-01

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

What we know about primary dysmenorrhea today: a critical review.

PubMed

Iacovides, Stella; Avidon, Ingrid; Baker, Fiona C

2015-01-01

Primary dysmenorrhea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynecological condition that affects between 45 and 95% of menstruating women. Despite the high prevalence, dysmenorrhea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. This review reports on current knowledge, particularly with regards to the impact and consequences of recurrent menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhea. Comprehensive literature searches on primary dysmenorrhea were performed using the electronic databases PubMed, Google Scholar and the Cochrane Library. Full-text manuscripts published between the years 1944 and 2015 were reviewed for relevancy and reference lists were cross-checked for additional relevant studies. In combination with the word 'dysmenorrhea' one or more of the following search terms were used to obtain articles published in peer-reviewed journals only: pain, risk factors, etiology, experimental pain, clinical pain, adenomyosis, chronic pain, women, menstrual cycle, hyperalgesia, pain threshold, pain tolerance, pain sensitivity, pain reactivity, pain perception, central sensitization, quality of life, sleep, treatment, non-steroidal anti-inflammatory drugs. Women with dysmenorrhea, compared with women without dysmenorrhea, have greater sensitivity to experimental pain both within and outside areas of referred menstrual pain. Importantly, the enhanced pain sensitivity is evident even in phases of the menstrual cycle when women are not experiencing menstrual pain, illustrating that long-term differences in pain perception extend outside of the painful menstruation phase. This enhanced pain sensitivity may increase susceptibility to other chronic pain conditions in later life; dysmenorrhea is a risk factor for fibromyalgia. Further, dysmenorrheic pain has an immediate negative impact on quality of life, for up to a few days every month. Women with primary dysmenorrhea have a significantly reduced quality of life, poorer mood and poorer sleep quality during menstruation compared with their pain-free follicular phase, and compared with the menstruation phase of pain-free control women. The prescribed first-line therapy for menstrual pain remains non-steroidal anti-inflammatory drugs, which are effective in relieving daytime and night-time pain. Further study is needed to determine whether effectively blocking dysmenorrheic pain ameliorates risk for the development of chronic pain disorders and to explore whether it is possible to prevent the development-and not just treat-severe dysmenorrheic pain in adolescent girls. In conclusion, we demonstrate the extensive multi-factorial impact of dysmenorrhea and we encourage and direct researchers to necessary future studies. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of ketamine on endogenous pain modulation in healthy volunteers.

PubMed

Niesters, Marieke; Dahan, Albert; Swartjes, Maarten; Noppers, Ingeborg; Fillingim, Roger B; Aarts, Leon; Sarton, Elise Y

2011-03-01

Inhibitory and facilitatory descending pathways, originating at higher central nervous system sites, modulate activity of dorsal horn nociceptive neurons, and thereby influence pain perception. Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain. The N-methyl-d-aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients. This effect is due to desensitization of sensitized N-methyl-d-aspartate receptors. Additionally, ketamine may modulate or enhance endogenous inhibitory control of pain perception. Diffuse noxious inhibitory control (DNIC) and offset analgesia (OA) are 2 mechanisms involved in descending inhibition. The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control. Ten healthy subjects (4 men/6 women) received a 1-hour placebo or S(+)-ketamine (40mg per 70kg) infusion on 2 separate occasions in random order. Upon the termination of the infusion, DNIC and OA responses were obtained. After placebo treatment, significant descending inhibition of pain responses was present for DNIC and OA. In contrast, after ketamine infusion, no DNIC was observed, but rather a significant facilitatory pain response (P<0.01); the OA response remained unchanged. These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation. The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC. Diffuse noxious inhibitory control responses following a 1-hour low-dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain?

PubMed Central

Ezenwa, Miriam O.; Molokie, Robert E.; Wang, Zaijie Jim; Yao, Yingwei; Suarez, Marie L.; Pullum, Cherese; Schlaeger, Judith M.; Fillingim, Roger B.; Wilkie, Diana J.

2014-01-01

Objectives Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. Methods A convenience sample (N=25, 18 women, mean age 38.5 ± 12.5 [20–58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. Results We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n=15), peripheral sensitization (n=1), a mix of central and peripheral sensitization (n=8), or no sensitization (n=1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. Discussion The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults. PMID:25581383

The epidemiology of back pain and its relationship with depression, psychosis, anxiety, sleep disturbances, and stress sensitivity: Data from 43 low- and middle-income countries.

PubMed

Stubbs, Brendon; Koyanagi, Ai; Thompson, Trevor; Veronese, Nicola; Carvalho, Andre F; Solomi, Marco; Mugisha, James; Schofield, Patricia; Cosco, Theodore; Wilson, Nicky; Vancampfort, Davy

Back pain (BP) is a leading cause of global disability. However, population-based studies investigating its impact on mental health outcomes are lacking, particularly among low- and middle-income countries (LMICs). Thus, the primary aims of this study were to: (1) determine the epidemiology of BP in 43 LMICs; (2) explore the relationship between BP and mental health (depression spectrum, psychosis spectrum, anxiety, sleep disturbances and stress). Data on 190,593 community-dwelling adults aged ≥18 years from the World Health Survey (WHS) 2002-2004 were analyzed. The presence of past-12 month psychotic symptoms and depression was established using questions from the Composite International Diagnostic Interview. Anxiety, sleep problems, stress sensitivity, and any BP or chronic BP (CBP) during the previous 30 days were also self-reported. Multivariable logistic regression analyses were undertaken. The overall prevalence of any BP and CBP were 35.1% and 6.9% respectively. Significant associations with any BP were observed for subsyndromal depression [OR (odds ratio)=2.21], brief depressive episode (OR=2.64), depressive episode (OR=2.88), psychosis diagnosis with symptoms (OR=2.05), anxiety (OR=2.12), sleep disturbance (OR=2.37) and the continuous variable of stress sensitivity. Associations were generally more pronounced for chronic BP. Our data establish that BP is associated with elevated mental health comorbidity in LMICs. Integrated interventions that address back pain and metal health comorbidities might be an important next step to tackle this considerable burden. Copyright © 2016 Elsevier Inc. All rights reserved.

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 involved in the pathological conditions of visceral pain, it is expected that better therapy will be achieved relatively soon to manage chronic visceral pain. PMID:19655104

Fish oil concentrate delays sensitivity to thermal nociception in mice

PubMed Central

Veigas, Jyothi M.; Williams, Paul J.; Halade, Ganesh; Rahman, Mizanur M.; Yoneda, Toshiyuki; Fernandes, Gabriel

2011-01-01

Fish oil has been used to alleviate pain associated with inflammatory conditions such as rheumatoid arthritis. The anti-inflammatory property of fish oil is attributed to the n-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid. Contrarily, vegetable oils such as safflower oil are rich in n-6 fatty acids which are considered to be mediators of inflammation. This study investigates the effect of n-3 and n-6 fatty acids rich oils as dietary supplements on the thermally induced pain sensitivity in healthy mice. C57Bl/6J mice were fed diet containing regular fish oil, concentrated fish oil formulation (CFO) and safflower oil (SO) for 6 months. Pain sensitivity was measured by plantar test and was correlated to the expression of acid sensing ion channels (ASICs), transient receptor potential vanilloid 1 (TRPV1) and c-fos in dorsal root ganglion cells. Significant delay in sensitivity to thermal nociception was observed in mice fed CFO compared to mice fed SO (p<0.05). A significant diminution in expression of ion channels such as ASIC1a (64%), ASIC13 (37%) and TRPV1 (56%) coupled with reduced expression of c-fos, a marker of neuronal activation, was observed in the dorsal root ganglion cells of mice fed CFO compared to that fed SO. In conclusion, we describe here the potential of fish oil supplement in reducing sensitivity to thermal nociception in normal mice. PMID:21345372

Pain reactivity and plasma beta-endorphin in children and adolescents with autistic disorder.

PubMed

Tordjman, Sylvie; Anderson, George M; Botbol, Michel; Brailly-Tabard, Sylvie; Perez-Diaz, Fernando; Graignic, Rozenn; Carlier, Michèle; Schmit, Gérard; Rolland, Anne-Catherine; Bonnot, Olivier; Trabado, Séverine; Roubertoux, Pierre; Bronsard, Guillaume

2009-08-26

Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma beta-endorphin levels and their relationship in a large group of individuals with autism. The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma beta-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Delta heart rate) was significantly greater than for controls (mean+/-SEM; 6.4+/-2.5 vs. 1.3+/-0.8 beats/min, P<0.05). Plasma beta-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity. The greater heart rate response to venepuncture and the elevated plasma beta-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain.

Pain Reactivity and Plasma β-Endorphin in Children and Adolescents with Autistic Disorder

PubMed Central

Tordjman, Sylvie; Anderson, George M.; Botbol, Michel; Brailly-Tabard, Sylvie; Perez-Diaz, Fernando; Graignic, Rozenn; Carlier, Michèle; Schmit, Gérard; Rolland, Anne-Catherine; Bonnot, Olivier; Trabado, Séverine; Roubertoux, Pierre; Bronsard, Guillaume

2009-01-01

Background Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma β-endorphin levels and their relationship in a large group of individuals with autism. Methodology/Principal Findings The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma β-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Δ heart rate) was significantly greater than for controls (mean±SEM; 6.4±2.5 vs. 1.3±0.8 beats/min, P<0.05). Plasma β-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity. Conclusions/Significance The greater heart rate response to venepuncture and the elevated plasma β-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain. PMID:19707566

Digit ratio (2D:4D) and postoperative pain perception.

PubMed

Kasielska-Trojan, Anna; Stabryła, Piotr; Antoszewski, Bogusław

2017-07-01

It has not been established whether sex differences in pain perception are influenced by prenatal sex hormones. Digit ratio as an indicator of prenatal hormone exposure can be used as a simple measure of the influence of prenatal hormones on pain sensitivity or perception in adulthood. The aim of this study was to determine a correlation between the 2D:4D ratio and pain perception in the postoperative period after rhinoplasty. A prospective cohort study of 100 patients (50 women of the mean age of 30.74±8.09years and 50 men of the mean age of 30.98±10.86years) who underwent posttraumatic rhinoplasty due to the nose trauma in Plastic, Reconstructive and Aesthetic Surgery Clinic. The following measurements were taken the day before a surgery: body height, waist and hip circumference, II and IV digits' lengths and body weight. All subjects filled in a questionnaire including 0-10-point VAS scales to assess postoperative pain 1h after an operation (AO), 6h AO, 12h AO, 24h AO and 48h AO. Women with low 2D:4D reported significantly more pain 1h after an operation than women with high 2D:4D. Similar correlation was observed for low 2D:4D in women 48h AO. In men, low 2D:4D was associated with lower postoperative pain 12h AO (p=0.029). In conclusion, we showed that low 2D:4D in women was associated with high postoperative pain, and low right 2D:4D in men was associated with low postoperative pain. This may suggest that intrauterine estrogen exposure makes women more resistant to pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Is Traumatic and Non-Traumatic Neck Pain Associated with Brain Alterations? - A Systematic Review.

PubMed

DePauw, Robby; Coppieters, Iris; Meeus, Mira; Caeyenberghs, Karen; Danneels, Lieven; Cagnie, Barbara

2017-05-01

Chronic neck pain affects 50% - 85% of people who have experienced an acute episode. This transition and the persistence of chronic complaints are believed to be mediated by brain alterations among different central mechanisms. This study aimed to systematically review and critically appraise the current existing evidence regarding structural and functional brain alterations in patients with whiplash associated disorders (WAD) and idiopathic neck pain (INP). Additionally, associations between brain alterations and clinical symptoms reported in neck pain patients were evaluated. Systematic review. The present systematic review was performed according to the PRISMA guidelines. PubMed, Web of Science, and Cochrane databases were searched. First, the obtained articles were screened based on title and abstract. Secondly, the screening was based on the full text. Risk of bias in included studies was investigated. Twelve studies met the inclusion criteria. Alterations in brain morphology and function, including perfusion, neurotransmission, and blood oxygenation level dependent-signal, were demonstrated in chronic neck pain patients. There is some to moderate evidence for both structural and functional brain alterations in patients with chronic neck pain. In contrast, no evidence for structural brain alterations in acute neck pain patients was found. Only 12 articles were included, which allows only cautious conclusions to be drawn. Brain alterations were observed in both patients with chronic WAD and chronic INP. Furthermore, more evidence exists for brain alterations in chronic WAD, and different underlying mechanisms might be present in both pathologies. In addition, pain and disability were correlated with the observed brain alterations. Accordingly, morphological and functional brain alterations should be further investigated in patients with chronic WAD and chronic INP with newer and more sensitive techniques, and associative clinical measurements seem indispensable in future research.

Presence of neuropathic pain may explain poor performances on olfactory testing in diabetes mellitus patients.

PubMed

Brady, Shauna; Lalli, Paul; Midha, Nisha; Chan, Ayechen; Garven, Alexandra; Chan, Cynthia; Toth, Cory

2013-07-01

Olfactory dysfunction in neurodegenerative conditions such as Parkinson's syndrome and Alzheimer's disease can hallmark disease onset. We hypothesized that patients with diabetes mellitus, a condition featuring peripheral and central neurodegeneration, would have decreased olfaction abilities. We examined participants with diabetic peripheral neuropathy, participants with diabetes without diabetic peripheral neuropathy, and control participants in blinded fashion using standardized Sniffin' Sticks. Diabetic peripheral neuropathy severity was quantified using the Utah Early Neuropathy Scale. Further subcategorization of diabetic peripheral neuropathy based on presence of neuropathic pain was performed with Douleur Neuropathique 4 Questionnaires. Participants with diabetes had decreased olfactory sensitivity, impaired olfactory discrimination abilities, and reduced odor identification skills when compared with controls. However, loss of olfaction ability was, at least partially, attributed to presence of neuropathic pain on subcategory assessment, although pain severity was not associated with dysfunction. Those participants with diabetes without diabetic peripheral neuropathy and those with diabetic peripheral neuropathy without neuropathic pain had similar olfactory function as controls in general. The presence of neuropathic pain, associated with limited attention and concentration, may explain at least a portion of the olfactory dysfunction witnessed in the diabetic patient population.

The value of physical examination in the diagnosis of hip osteoarthritis.

PubMed

Chong, Timothy; Don, Darren W; Kao, Ming-Chih; Wong, Dexter; Mitra, Raj

2013-01-01

To compare the sensitivity of physical examination (internal rotation of the hip) with radiographs (using the Kellgren-Lawrence grading scale) in the diagnosis of clinically significant hip osteoarthritis. Case Series, Retrospective chart review of hip pain patients that underwent fluoroscopically guided hip steroid and anesthetic injections. 10 patients with hip pain patients seen at an academic outpatient center over a 2 year period were analyzed. Fluoroscopically guided hip steroid and anesthetic injection. Pain relief and change in VAS pain score after intra-articular hip steroid and lidocaine injection was the main outcome measure. Based on Fisher's exact test, there was no association between severity of radiographic hip arthritis and pain relief with intra-articular anesthetic/steroid injection (p=0.45). Physical examination (provocative hip internal rotation) however was associated with a significant decrease in VAS pain score after intra-articular lidocaine and corticosteroid hip injection (p=0.022). Simple hip radiographs alone are not sufficient to diagnose clinically significant hip osteoarthritis. Physical examination (hip internal rotation) was found to be more accurate than simple radiographs in the diagnosis of clinically significant hip osteoarthritis. Radiographs seem to best utilized when they are an extension of the physical examination and patient history.

Hemifacial Pain and Hemisensory Disturbance Referred from Occipital Neuralgia Caused by Pathological Vascular Contact of the Greater Occipital Nerve

PubMed Central

Choi, Jin-gyu

2017-01-01

Here we report a unique case of chronic occipital neuralgia caused by pathological vascular contact of the left greater occipital nerve. After 12 months of left-sided, unremitting occipital neuralgia, a hypesthesia and facial pain developed in the left hemiface. The decompression of the left greater occipital nerve from pathological contacts with the occipital artery resulted in immediate relief for hemifacial sensory change and facial pain, as well as chronic occipital neuralgia. Although referral of pain from the stimulation of occipital and cervical structures innervated by upper cervical nerves to the frontal head of V1 trigeminal distribution has been reported, the development of hemifacial sensory change associated with referred trigeminal pain from chronic occipital neuralgia is extremely rare. Chronic continuous and strong afferent input of occipital neuralgia caused by pathological vascular contact with the greater occipital nerve seemed to be associated with sensitization and hypersensitivity of the second-order neurons in the trigeminocervical complex, a population of neurons in the C2 dorsal horn characterized by receiving convergent input from dural and cervical structures. PMID:28331643

Hemifacial Pain and Hemisensory Disturbance Referred from Occipital Neuralgia Caused by Pathological Vascular Contact of the Greater Occipital Nerve.

PubMed

Son, Byung-Chul; Choi, Jin-Gyu

2017-01-01

Here we report a unique case of chronic occipital neuralgia caused by pathological vascular contact of the left greater occipital nerve. After 12 months of left-sided, unremitting occipital neuralgia, a hypesthesia and facial pain developed in the left hemiface. The decompression of the left greater occipital nerve from pathological contacts with the occipital artery resulted in immediate relief for hemifacial sensory change and facial pain, as well as chronic occipital neuralgia. Although referral of pain from the stimulation of occipital and cervical structures innervated by upper cervical nerves to the frontal head of V1 trigeminal distribution has been reported, the development of hemifacial sensory change associated with referred trigeminal pain from chronic occipital neuralgia is extremely rare. Chronic continuous and strong afferent input of occipital neuralgia caused by pathological vascular contact with the greater occipital nerve seemed to be associated with sensitization and hypersensitivity of the second-order neurons in the trigeminocervical complex, a population of neurons in the C2 dorsal horn characterized by receiving convergent input from dural and cervical structures.

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

PubMed

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

2015-04-01

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

Cross-modal and modality-specific expectancy effects between pain and disgust

PubMed Central

Sharvit, Gil; Vuilleumier, Patrik; Delplanque, Sylvain; Corradi-Dell’ Acqua, Corrado

2015-01-01

Pain sensitivity increases when a noxious stimulus is preceded by cues predicting higher intensity. However, it is unclear whether the modulation of nociception by expectancy is sensory-specific (“modality based”) or reflects the aversive-affective consequence of the upcoming event (“unpleasantness”), potentially common with other negative events. Here we compared expectancy effects for pain and disgust by using different, but equally unpleasant, nociceptive (thermal) and olfactory stimulations. Indeed both pain and disgust are aversive, associated with threat to the organism, and processed in partly overlapping brain networks. Participants saw cues predicting the unpleasantness (high/low) and the modality (pain/disgust) of upcoming thermal or olfactory stimulations, and rated the associated unpleasantness after stimuli delivery. Results showed that identical thermal stimuli were perceived as more unpleasant when preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was found for olfactory disgust. Critically, cross-modal expectancy effects were observed on inconsistent trials when thermal stimuli were preceded by high-disgust cues or olfactory stimuli preceded by high-pain cues. However, these effects were stronger in consistent than inconsistent conditions. Taken together, our results suggest that expectation of an unpleasant event elicits representations of both its modality-specific properties and its aversive consequences. PMID:26631975

Clinical predictors of time to return to competition following hamstring injuries.

PubMed

Guillodo, Yannick; Here-Dorignac, Caroline; Thoribé, Bertrand; Madouas, Gwénaelle; Dauty, Marc; Tassery, Francois; Saraux, Alain

2014-07-01

hamstring strain injuries are the most common sports-related muscle injuries and one of the main causes of missed sporting events. clinical findings reflecting hamstring injury severity at presentation predict time to sports resumption. cohort study (prognosis); Level of evidence, 2. five sports medicine specialists at four sports medicine centers prospectively evaluated 120 athletes within 5 days of acute hamstring injury. Patients were interviewed and asked to evaluate their worst pain on a visual analog scale (VAS). Four physical criteria were assessed at baseline: bruising, tenderness to palpation, pain upon isometric contraction, and pain upon passive straightening. The same standardized rehabilitation protocol was used in all patients. A standardized telephone interview was conducted 45 days after the injury to determine the time to-full recovery (≤40 days or >40 days). by univariate analysis, clinical criteria associated with a full recovery time >40 days were VAS pain score greater than 6, popping sound injury, pain during everyday activities for more than 3 days, bruising, and greater than 15° motion-range limitation. By multivariate analysis, only VAS pain score and pain during everyday activities were significantly associated with time to recovery >40 days (53% sensitivity, 95% specificity). the initial examination provides valuable information that can be used to predict the time to full recovery after acute hamstring injuries in athletes.

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

PubMed

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

2011-01-01

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

Burning Eye Syndrome: Do Neuropathic Pain Mechanisms Underlie Chronic Dry Eye?

PubMed

Kalangara, Jerry P; Galor, Anat; Levitt, Roy C; Felix, Elizabeth R; Alegret, Ramon; Sarantopoulos, Constantine D

2016-04-01

Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome." A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized. We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome." © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.

PubMed

Gupta, Arpana; Woodworth, Davis C; Ellingson, Benjamin M; Rapkin, Andrea J; Naliboff, Bruce; Kilpatrick, Lisa A; Stains, Jean; Masghati, Salome; Tillisch, Kirsten; Mayer, Emeran A; Labus, Jennifer S

2018-05-01

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Autoerythrocyte sensitization syndrome presenting with general neurodermatitis

PubMed Central

Oh, In Young; Ko, Eun Jung

2013-01-01

Autoerythrocyte sensitization syndrome (AES) was first described by Gardner and Diamond in 1955, when four women with painful bruising were depicted. Patients with AES typically present with the development of recurrent, spontaneous, painful ecchymosis, frequently preceded by a prodrome of pain or itching of the skin. The patients are sensitive to their own red blood cells injected intradermally, and underlying coagulopathies are thought to be absent. We introduce a 70-year-old woman presenting with recurrent episodes of painful bruising on the trunk and extremities. PMID:23956968

Pain perception in people with Down syndrome: a synthesis of clinical and experimental research

PubMed Central

McGuire, Brian E.; Defrin, Ruth

2015-01-01

People with an intellectual disability experience both acute and chronic pain with at least the same frequency as the general population. However, considerably less is known about the pain perception of people with Down syndrome. In this review paper, we evaluated the available clinical and experimental evidence. Some experimental studies of acute pain have indicated that pain threshold was higher than normal but only when using a reaction time method to measure pain sensitivity. However, when reaction time is not part of the calculation of the pain threshold, pain sensitivity in people with Down syndrome is in fact lower than normal (more sensitive to pain). Clinical studies of chronic pain have shown that people with an intellectual disability experience chronic pain and within that population, people with Down syndrome also experience chronic pain, but the precise prevalence of chronic pain in Down syndrome has yet to be established. Taken together, the literature suggests that people with Down syndrome experience pain, both acute and chronic, with at least the same frequency as the rest of the population. Furthermore, the evidence suggests that although acute pain expression appears to be delayed, once pain is registered, there appears to be a magnified pain response. We conclude by proposing an agenda for future research in this area. PMID:26283936

Treatment of hemimandibular paresthesia in a patient with bisphosphonate-related osteonecrosis of the jaw (BRONJ) by combining surgical resection and PRGF-Endoret.

PubMed

Anitua, E; Begoña, L; Orive, G

2013-12-01

We report a case of a 50-year-old patient with bisphosphonate-related osteonecrosis of the jaws (BRONJs) whose symptoms included severe pain and hemimandibular paraesthesia. The treatment included resection of necrotic bone and the application of plasma rich in growth factors (PRGF(®)-Endoret(®)). We closed the ulcer in the soft tissue and her pain and paraesthesia improved. One year postoperatively sensitivity was totally recovered, pain was absent and bone was partially regenerated. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

MRI assessed pancreatic morphology and exocrine function are associated with disease burden in chronic pancreatitis.

PubMed

Madzak, Adnan; Olesen, Søren Schou; Lykke Poulsen, Jakob; Bolvig Mark, Esben; Mohr Drewes, Asbjørn; Frøkjær, Jens Brøndum

2017-11-01

The aim of this study was to explore the association between morphological and functional secretin-stimulated MRI parameters with hospitalization, quality of life (QOL), and pain in patients with chronic pancreatitis (CP). This prospective cohort study included 82 patients with CP. Data were obtained from clinical information, QOL, and pain as assessed by questionnaires (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and modified Brief Pain Inventory short form). Secretin-stimulated MRI morphological parameters included pancreatic gland volume, main pancreatic duct diameter, the modified Cambridge Classification of Duct Abnormality, apparent diffusion coefficient, fat signal fraction, and the pancreatic secretion volume as a functional parameter. The primary outcomes were time to first hospitalization related to the CP, as well as annual hospitalization frequency and duration. The secondary outcomes were pain severity, QOL, and pain interference scores. A main pancreatic duct diameter below 5 mm was associated with reduced time to first hospitalization (hazard ratio=2.06; 95% confidence interval: 1.02-4.17; P=0.043). Pancreatic secretion volume was correlated with QOL (r=0.31; P=0.0072) and pain interference score (r=-0.27; P=0.032), and fecal elastase was also correlated with QOL (r=0.28; P=0.017). However, functional and morphological findings were not related to pain intensity. Advanced pancreatic imaging techniques may be a highly sensitive tool for prognostication and monitoring of disease activity and its consequences.

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

Use of the Central Sensitization Inventory (CSI) as a treatment outcome measure for patients with chronic spinal pain disorder in a functional restoration program.

PubMed

Neblett, Randy; Hartzell, Meredith M; Williams, Mark; Bevers, Kelley R; Mayer, Tom G; Gatchel, Robert J

2017-12-01

The Central Sensitization Inventory (CSI) is a valid and reliable patient-reported instrument designed to identify patients whose presenting symptoms may be related to central sensitization (CS). Part A of the CSI measures a full array of 25 somatic and emotional symptoms associated with CS, and Part B asks if patients have previously been diagnosed with one or more specific central sensitivity syndromes (CSSs) and related disorders. The CSI has previously been validated in a group of patients with chronic pain who were screened by a trained psychiatrist for specific CSS diagnoses. It is currently unknown if the CSI can be a useful treatment-outcome assessment tool for patients with chronic spinal pain disorder (CSPD) who are not screened for comorbid CSSs. It is known, however, that previous studies have identified CS-related symptoms, and comorbid CSSs, in subsets of patients with CSPDs. Studies have also shown that CS-related symptoms can be influenced by cognitive and psychosocial factors, including abuse history in both childhood and adulthood, sleep disturbance, catastrophic and fear-avoidant cognitions, and symptoms of depression and anxiety. This study aimed to evaluate CSI scores, and their associations with other clinically relevant psychosocial variables, in a cohort of patients with CSPD who entered and completed a functional restoration program. A retrospective study of prospectively collected data from a cohort study of patients with CSPD, who completed the CSI at admission to, and discharge from, an interdisciplinary function restoration program (FRP) was carried out. A cohort of 763 patients with CSPD comprised the study sample. Clinical interviews evaluated mood disorders and abuse history. A series of self-reported measures evaluated comorbid psychosocial symptoms, including pain intensity, pain-related anxiety, depressive symptoms, somatization symptoms, perceived disability, and sleep disturbance, at FRP admission and discharge. Patients were grouped into five severity level groups, from mild to extreme, based on total CSI scores, at FRP admission, and then again at discharge. The FRP included a quantitatively directed and medically supervised exercise process, as well as a multimodal psychosocial disability management component. The CSI severity groups were strongly associated with Major Depressive Disorder and previous abuse history (p<.01), which are known risk factors for CS-related symptoms and diagnoses. The CSI scores were also strongly associated with patient-reported CSS diagnoses on CSI Part B. The percentage of patients who reported a comorbid CSS diagnosis increased in each higher CSI-severity group, from 11% in the Subclinical group, to 56% in the Extreme group. The CSI severity groups were significantly related to other CS-related patient-reported symptoms, including pain intensity, pain-related anxiety, depressive symptoms, somatization symptoms, perceived disability, and sleep disturbance (p's<.001). The CSI scores, along with all other psychosocial measures, decreased at treatment discharge. In the present study, admission CSI scores were highly associated with previous CSS diagnoses, CS-related symptoms, and clinically relevant patient-reported psychosocial variables. All psychosocial variables, as well as scores on the CSI, were significantly improved at FRP discharge. The CSI may have important clinical utility, as a screener and as a treatment outcome measure, for patients with CSPD participating in an interdisciplinary FRP. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of PCA Strategies on Pain Intensity and Functional Assessment Measures in Adults with Sickle Cell Disease during Hospitalized Vaso-Occlusive Episodes

PubMed Central

Dampier, Carlton D.; Wager, Carrie G.; Harrison, Ryan; Hsu, Lewis L.; Minniti, Caterina P.; Smith, Wally R.

2012-01-01

Clinical trials of sickle cell disease (SCD) pain treatment usually observe only small decrements in pain intensity during the course of hospitalization. Sub-optimal analgesic management and inadequate pain assessment methods are possible explanations for these findings. In a search for better methods for assessing inpatient SCD pain in adults, we examined several pain intensity and interference measures in both arms of a randomized controlled trial comparing two different opioid PCA therapies. Based upon longitudinal analysis of pain episodes, we found that scores from daily average Visual Analogue Scales (VAS) and several other measures, especially the Brief Pain Inventory (BPI), were sensitive to change in daily improvements in pain intensity associated with resolution of vaso-occlusive pain. In this preliminary trial, the low demand, high basal infusion (LDHI) strategy demonstrated faster, larger improvements in various measures of pain than the high demand, low basal infusion (HDLI) strategy for opioid PCA dosing, however, verification in larger studies is required. The measures and statistical approaches used in this analysis may facilitate design, reduce sample size, and improve analyses of treatment response in future SCD clinical trials of vaso-occlusive episodes. PMID:22886853

Cognitive Performance Is Related to Central Sensitization and Health-related Quality of Life in Patients with Chronic Whiplash-Associated Disorders and Fibromyalgia.

PubMed

Coppieters, Iris; Ickmans, Kelly; Cagnie, Barbara; Nijs, Jo; De Pauw, Robby; Noten, Suzie; Meeus, Mira

2015-01-01

A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients. (1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups. A case-control study was conducted. The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp. Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN]). Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P < 0.017). CPM was comparable between the 3 groups. Cognitive performance was significantly related to central pain modulation (deep-tissue hyperalgesia, TS, CPM) as well as to self-reported health-related QoL (P < 0.05). Decreased cognitive performance was related to deficient central pain modulation in healthy controls. Further, significant correlations between decreased cognitive performance and reduced health-related QoL were revealed among all study groups. Additionally, FM patients showed correlations between cognitive impairment and increased health-related QoL. Remarkably, impaired selective attention and working memory were related to less TS, whereas impaired sustained attention was correlated with dysfunctional CPM in FM patients. Based on the current cross-sectional study no firm conclusions can be drawn on the causality of the relations. In conclusion, this paper has demonstrated significant cognitive deficits, signs of CS, and reduced health-related QoL in chronic WAD and FM patients compared to healthy individuals. Significant relations between cognitive performance and CS as well as health-related QoL were demonstrated. These results provide preliminary evidence for the clinical importance of objectively measured cognitive deficits in patients with chronic WAD and FM. Chronic pain, fibromyalgia, whiplash, central sensitization, conditioned pain modulation, temporal summation, cognition, quality of life.

Streamlining the Evaluation of Low Back Pain in Children

PubMed Central

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

2008-01-01

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

Symptoms and signs associated with benign and malignant proximal fibular tumors: a clinicopathological analysis of 52 cases.

PubMed

Sun, Tao; Wang, Lingxiang; Guo, Changzhi; Zhang, Guochuan; Hu, Wenhai

2017-05-02

Malignant tumors in the proximal fibula are rare but life-threatening; however, biopsy is not routine due to the high risk of peroneal nerve injury. Our aim was to determine preoperative clinical indicators of malignancy. Between 2004 and 2016, 52 consecutive patients with proximal fibular tumors were retrospectively reviewed. Details of the clinicopathological characteristics including age, gender, location of tumors, the presenting symptoms, the duration of symptoms, and pathological diagnosis were collected. Descriptive statistics were calculated, and univariate and multivariate regression were performed. Of these 52 patients, 84.6% had benign tumors and 15.4% malignant tumors. The most common benign tumors were osteochondromas (46.2%), followed by enchondromas (13.5%) and giant cell tumors (13.5%). The most common malignancy was osteosarcomas (11.5%). The most common presenting symptoms were a palpable mass (52.0%) and pain (46.2%). Pain was the most sensitive (100%) and fourth specific (64%); both high skin temperature and peroneal nerve compression had the highest specificity (98%) and third sensitivity (64%); change in symptoms had the second highest specificity (89%) while 50% sensitivity. Using multivariate regression, palpable pain, high skin temperature, and peroneal nerve compression symptoms were predictors of malignancy. Most tumors in the proximal fibula are benign, and the malignancy is rare. Palpable pain, peroneal nerve compression symptoms, and high skin temperature were specific in predicting malignancy.

Neonatal Sleep Restriction Increases Nociceptive Sensitivity in Adolescent Mice.

PubMed

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

2018-03-01

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

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

PubMed

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

2014-01-01

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

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

PubMed Central

2013-01-01

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

Pediatric fibromyalgia.

PubMed

Buskila, Dan

2009-05-01

Fibromyalgia is an idiopathic chronic pain syndrome defined by widespread nonarticular musculoskeletal pain and generalized tender points. The syndrome is associated with a constellation of symptoms, including fatigue, nonrefreshing sleep, irritable bowel, and more. Central nervous system sensitization is a major pathophysiologic aspect of fibromyalgia; in addition, various external stimuli such as trauma and stress may contribute to development of the syndrome. Fibromyalgia is most common in midlife, but may be seen at any age. This article reviews the epidemiology, clinical characteristics, etiology, management, and outcome of pediatric fibromyalgia.

Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease.

PubMed

Dai, Feng; Belfer, Inna; Schwartz, Carolyn E; Banco, Robert; Martha, Julia F; Tighioughart, Hocine; Tromanhauser, Scott G; Jenis, Louis G; Kim, David H

2010-11-01

Surgical treatment for lumbar degenerative disc disease (DDD) has been associated with highly variable results in terms of postoperative pain relief and functional improvement. Many experts believe that DDD should be considered a chronic pain disorder as opposed to a degenerative disease. Genetic variation of the catechol-O-methyltransferase (COMT) gene has been associated with variation in human pain sensitivity and response to analgesics in previous studies. To determine whether genetic variation of COMT is associated with clinical outcome after surgical treatment for DDD. Prospective genetic association study. Sixty-nine patients undergoing surgical treatment for lumbar DDD. Diagnosis was based on documentation of chronic disabling low back pain (LBP) present for a minimum of 6 months and unresponsive to supervised nonoperative treatment, including activity modification, medication, physical therapy, and/or injection therapy. Plain radiographs and magnetic resonance imaging revealed intervertebral disc desiccation, tears, and/or collapse without focal herniation, nerve root compression, stenosis, spondylolisthesis, spondylolysis, or alternative diagnoses. Oswestry Disability Index (ODI) and visual analog score (VAS) for LBP. Surgical treatment included 65 instrumented fusions and four disc arthroplasty procedures. All patients completed preoperative and 1-year postoperative ODI questionnaires. DNA was extracted from a sample of venous blood, and genotype analysis was performed for five common COMT single nucleotide polymorphisms (SNPs). Potential genetic association between these COMT SNPs and the primary outcome variable, 1-year change in ODI, was investigated using both single-marker and haplotype association analyses. Association with VAS scores for LBP was analyzed as a secondary outcome variable. Single-marker analysis revealed that the COMT SNP rs4633 was significantly associated with greater improvement in ODI score 1 year after surgery (p=.03), with individuals homozygous for the less common "T" allele demonstrating the largest improvement in ODI. Haplotype analysis of four COMT SNPs, rs6269, rs4633, rs4818, and rs4680, also identified a common haplotype "ATCA" (haplotype frequency of 39.3% in the study population) associated with greater improvement in ODI (p=.046). The greatest mean improvement in ODI was observed in patients homozygous for the "ATCA"COMT haplotype. A nonsignificant trend was observed between SNP rs4633 and greater improvement in VAS score for LBP. This is the first study to report an association between surgical treatment success in DDD patients and genetic variation in the putative pain sensitivity gene COMT. These findings require replication in other DDD populations but suggest that genetic testing for pain-relevant genetic markers such as COMT may provide useful clinical information in terms of predicting outcome after surgery for patients diagnosed with DDD. Copyright © 2010 Elsevier Inc. All rights reserved.

Deficient pain modulatory systems in patients with mild traumatic brain and chronic post-traumatic headache: implications for its mechanism.

PubMed

Defrin, Ruth; Riabinin, Miri; Feingold, Yelena; Schreiber, Shaul; Pick, Chaim G

2015-01-01

Although the prevalence rate of chronic post-traumatic headache (CPTHA) after mild traumatic brain injury (TBI) reaches up to 95%, its mechanism is unknown, and little is known about the characteristics of the pain system in this condition. Our aim was to investigate the capabilities of two pain modulatory systems among individuals with CPTHA and study their association with CPTHA, here for the first time. Forty-six subjects participated; 16 with TBI and CPTHA, 12 with TBI without CPTHA, and 18 healthy controls. Testing included the measurement of heat-pain (HPT) and pressure-pain (PPT) thresholds in the forehead and forearm, pain adaptation to tonic noxious heat, and conditioned pain modulation (CPM).The participants completed a post-traumatic stress disorder (PTSD) questionnaire. The two TBI groups did not differ in the TBI and background characteristics. However, TBI patients with CPTHA had significantly higher HPT and lower PPT in the cranium and higher PTSD symptomatology than TBI patients without CPTHA and healthy controls. Adaptation to pain and CPM were diminished in the CPTHA group compared with the two control groups. The intensity of CPTHA correlated negatively with cranial PPT, magnitude of pain adaptation, and CPM. CPTHA intensity correlated positively with PTSD symptomatology. CPTHA appears to be characterized by cranial hyperalgesia and dysfunctional pain modulation capabilities, which are associated with CPTHA magnitude. It is concluded that damage to pain modulatory systems along with chronic cranial sensitization underlies the development of CPTHA. PTSD may reinforce CPTHA and vice versa. Clinical implications are discussed.

Deficient Pain Modulatory Systems in Patients with Mild Traumatic Brain and Chronic Post-Traumatic Headache: Implications for its Mechanism

PubMed Central

Riabinin, Miri; Feingold, Yelena; Schreiber, Shaul; Pick, Chaim G.

2015-01-01

Abstract Although the prevalence rate of chronic post-traumatic headache (CPTHA) after mild traumatic brain injury (TBI) reaches up to 95%, its mechanism is unknown, and little is known about the characteristics of the pain system in this condition. Our aim was to investigate the capabilities of two pain modulatory systems among individuals with CPTHA and study their association with CPTHA, here for the first time. Forty-six subjects participated; 16 with TBI and CPTHA, 12 with TBI without CPTHA, and 18 healthy controls. Testing included the measurement of heat-pain (HPT) and pressure-pain (PPT) thresholds in the forehead and forearm, pain adaptation to tonic noxious heat, and conditioned pain modulation (CPM).The participants completed a post-traumatic stress disorder (PTSD) questionnaire. The two TBI groups did not differ in the TBI and background characteristics. However, TBI patients with CPTHA had significantly higher HPT and lower PPT in the cranium and higher PTSD symptomatology than TBI patients without CPTHA and healthy controls. Adaptation to pain and CPM were diminished in the CPTHA group compared with the two control groups. The intensity of CPTHA correlated negatively with cranial PPT, magnitude of pain adaptation, and CPM. CPTHA intensity correlated positively with PTSD symptomatology. CPTHA appears to be characterized by cranial hyperalgesia and dysfunctional pain modulation capabilities, which are associated with CPTHA magnitude. It is concluded that damage to pain modulatory systems along with chronic cranial sensitization underlies the development of CPTHA. PTSD may reinforce CPTHA and vice versa. Clinical implications are discussed. PMID:25068510

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

PubMed Central

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

2012-01-01

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

Mindfulness Meditation and Cognitive Behavioral Therapy Intervention Reduces Pain Severity and Sensitivity in Opioid-Treated Chronic Low Back Pain: Pilot Findings from a Randomized Controlled Trial.

PubMed

Zgierska, Aleksandra E; Burzinski, Cindy A; Cox, Jennifer; Kloke, John; Stegner, Aaron; Cook, Dane B; Singles, Janice; Mirgain, Shilagh; Coe, Christopher L; Bačkonja, Miroslav

2016-10-01

To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). Outpatient. Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen's d = 0.86), and decreased pain sensitivity to thermal stimuli (P < 0.05), without adverse events. Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits. Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

PubMed Central

Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

2017-01-01

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

Age-related differences in factors associated with cervical spine injuries in children.

PubMed

Leonard, Julie C; Jaffe, David M; Olsen, Cody S; Kuppermann, Nathan

2015-04-01

The Pediatric Emergency Care Applied Research Network (PECARN) investigators previously identified risk factors associated with cervical spine injuries (CSIs) in children. Anatomic maturation and age-related variation in mechanisms of injury suggested the need to explore factors separately for younger versus older children. The purpose of this substudy was to investigate CSI risk factors in age subgroups within the PECARN study cohort. This was an age-stratified case-control analysis of children younger than 16 years presenting to 17 PECARN hospitals following blunt trauma between January 1, 2000 and December 31, 2004. Data were abstracted for children with CSIs and randomly selected CSI-free children. Age-stratified multivariable logistic regression was performed to identify factors associated with CSI within three age groups: younger than 2, 2 to 7, and 8 to 15 years. Sensitivity and specificity for CSI were estimated for both the age-specific and original (altered mental status, focal neurologic findings, neck pain, torticollis, substantial torso injury, predisposing conditions, diving, and high-risk motor vehicle crash [MVC]) models. Among 540 children with CSIs, 27 were younger than 2 years, 140 were 2 to 7 years, and 373 were 8 to 15 years. Focal neurologic deficits and high-risk MVC were associated with CSIs in all age-specific models. Other age-specific factors included the following: younger than 2 years, none; 2 to 7 years, altered mental status, neck pain, torticollis; and 8 to 15 years, altered mental status, neck pain, diving. Age-specific models had comparable sensitivity to the original model among the older groups, but had lower sensitivity and higher specificity among the youngest children. While this analysis supports the original PECARN model for CSI, there were subtle age variations in factors associated with CSIs in children that warrant future investigation. © 2015 by the Society for Academic Emergency Medicine.

Racial-Ethnic Disparities in Opioid Prescriptions at Emergency Department Visits for Conditions Commonly Associated with Prescription Drug Abuse.

PubMed

Singhal, Astha; Tien, Yu-Yu; Hsia, Renee Y

2016-01-01

Prescription drug abuse is a growing problem nationally. In an effort to curb this problem, emergency physicians might rely on subjective cues such as race-ethnicity, often unknowingly, when prescribing opioids for pain-related complaints, especially for conditions that are often associated with drug-seeking behavior. Previous studies that examined racial-ethnic disparities in opioid dispensing at emergency departments (EDs) did not differentiate between prescriptions at discharge and drug administration in the ED. We examined racial-ethnic disparities in opioid prescription at ED visits for pain-related complaints often associated with drug-seeking behavior and contrasted them with conditions objectively associated with pain. We hypothesized a priori that racial-ethnic disparities will be present among opioid prescriptions for conditions associated with non-medical use, but not for objective pain-related conditions. Using data from the National Hospital Ambulatory Medical Care Survey for 5 years (2007-2011), the odds of opioid prescription during ED visits made by non-elderly adults aged 18-65 for 'non-definitive' conditions (toothache, back pain and abdominal pain) or 'definitive' conditions (long-bone fracture and kidney stones) were modeled. Opioid prescription at discharge and opioid administration at the ED were the primary outcomes. We found significant racial-ethnic disparities, with non-Hispanic Blacks being less likely (adjusted odds ratio ranging from 0.56-0.67, p-value < 0.05) to receive opioid prescription at discharge during ED visits for back pain and abdominal pain, but not for toothache, fractures and kidney stones, compared to non-Hispanic whites after adjusting for other covariates. Differential prescription of opioids by race-ethnicity could lead to widening of existing disparities in health, and may have implications for disproportionate burden of opioid abuse among whites. The findings have important implications for medical provider education to include sensitization exercises towards their inherent biases, to enable them to consciously avoid these biases from defining their practice behavior.

Women experience greater heat pain adaptation and habituation than men.

PubMed

Hashmi, Javeria A; Davis, Karen D

2009-10-01

It is not clear how males and females cope with pain over time and how sensory and emotional qualities fluctuate from moment to moment, although studies of pain at discrete time points suggest that women are more pain sensitive than men. Therefore, we developed a new broader-based pain model that incorporates a temporally continuous assessment of multiple pain dimensions across sensory and affective dimensions, and normalized peak pain intensity to unmask sex differences that may otherwise be confounded by inter-individual variability in pain sensitivity. We obtained continuous ratings of pain, burning, sharp, stinging, cutting, and annoyance evoked by repeated prolonged noxious heat stimuli in 32 subjects. Strikingly, females reported more pain than males at the outset of the first exposure to pain, but then experienced less pain and annoyance than males as a painful stimulus was sustained and with repeated stimulation. Patterns of pain and annoyance attenuation in women resembled the attenuation of sharp, stinging and cutting sensations, whereas patterns of pain and annoyance in men resembled burning sensations. Taken together, these data demonstrate a prominent sex difference in the time course of pain. Notably only females demonstrate adaptation and habituation that allow them to experience less pain over time. These findings suggest a sexual dichotomy in mechanisms underlying pain intensity and annoyance that could involve specific quality-linked mechanisms. Importantly, temporal processing of pain differs between males and females when adjusted for sex differences in pain sensitivity. Our findings provide insight into sex differences in tonic and possibly chronic pains.

Effect of gabapentin on morphine consumption and pain after surgical debridement of burn wounds: a double-blind randomized clinical trial study.

PubMed

Rimaz, Siamak; Alavi, Cyrus Emir; Sedighinejad, Abbas; Tolouie, Mohammad; Kavoosi, Sharareh; Koochakinejad, Leila

2012-01-01

Burn pain is recognized as being maximal during therapeutic procedures, and wound debridement can be more painful than the burn injury itself. Uncontrolled acute burn pain increases the stress response and the incidence of chronic pain and associated depression. Although opiates are excellent analgesics, they do not effectively prevent central sensitization to pain. The anticonvulsant gabapentin has been proven effective for treating neuropathic pain in large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models with central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of this study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in burn patients undergoing resection of burn wounds. In a randomized, double-blind, placebo-controlled study, 50 burn patients received a single oral dose of gabapentin (1200mg) or placebo 2h before surgery. Anesthesia was induced with propofol and fentanyl and maintained by infusingpropofol, remifentanil, and 50% N2O in O2. All patients received patient-controlled analgesia with morphine at doses of 2.5 mg bolus and a lock-out time of 10 min for 24h before the operation. Pain was assessed on a visual analog scale (VAS) at rest and during movement at 1,4,8,12,16,20, and 24 h before the operation. Heart rate, oxygen saturation, mean arterial blood pressure, respiratory rate, sedation score, and morphine consumption were studied. All the enrolled patients were able to complete the study; therefore, data from 50 patients wereanalyzed. The VAS scores at rest andduring movement at 1,4,8,12,16,20, and 24 h after the operation were significantly lower in the gabapentin group than in the placebo group (P < 0.05). Morphine consumption was significantly lessr in the gabapentin group than in the placebo group (P < 0.05). Sedation scores were similar in the 2 groups at all measured times. There were no differences in adverse effects between the groups. A single oral dose of 1200mg gabapentin resulted in a substantial reduction in postoperative morphine consumption and pain scores after surgical debridement in burn patients.

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

PubMed

Sutton, Blair C; Opp, Mark R

2014-03-01

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

Sex differences and hormonal modulation of deep tissue pain

PubMed Central

Traub, Richard J.; Ji, Yaping

2013-01-01

Women disproportionately suffer from many deep tissue pain conditions. Experimental studies show that women have lower pain thresholds, higher pain ratings and less tolerance to a range of painful stimuli. Most clinical and epidemiological reports suggest female gonadal hormones modulate pain for some, but not all, conditions. Similarly, animal studies support greater nociceptive sensitivity in females in many deep tissue pain models. Gonadal hormones modulate responses in primary afferents, dorsal horn neurons and supraspinal sites, but the direction of modulation is variable. This review will examine sex differences in deep tissue pain in humans and animals focusing on the role of gonadal hormones (mainly estradiol) as an underlying component of the modulation of pain sensitivity. PMID:23872333

Overcoming pain thresholds with multilevel models-an example using quantitative sensory testing (QST) data.

PubMed

Hirschfeld, Gerrit; Blankenburg, Markus R; Süß, Moritz; Zernikow, Boris

2015-01-01

The assessment of somatosensory function is a cornerstone of research and clinical practice in neurology. Recent initiatives have developed novel protocols for quantitative sensory testing (QST). Application of these methods led to intriguing findings, such as the presence lower pain-thresholds in healthy children compared to healthy adolescents. In this article, we (re-) introduce the basic concepts of signal detection theory (SDT) as a method to investigate such differences in somatosensory function in detail. SDT describes participants' responses according to two parameters, sensitivity and response-bias. Sensitivity refers to individuals' ability to discriminate between painful and non-painful stimulations. Response-bias refers to individuals' criterion for giving a "painful" response. We describe how multilevel models can be used to estimate these parameters and to overcome central critiques of these methods. To provide an example we apply these methods to data from the mechanical pain sensitivity test of the QST protocol. The results show that adolescents are more sensitive to mechanical pain and contradict the idea that younger children simply use more lenient criteria to report pain. Overall, we hope that the wider use of multilevel modeling to describe somatosensory functioning may advance neurology research and practice.

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

Increased pain sensitivity but normal function of exercise induced analgesia in hip and knee osteoarthritis--treatment effects of neuromuscular exercise and total joint replacement.

PubMed

Kosek, E; Roos, E M; Ageberg, E; Nilsdotter, A

2013-09-01

To assess exercise induced analgesia (EIA) and pain sensitivity in hip and knee osteoarthritis (OA) and to study the effects of neuromuscular exercise and surgery on these parameters. The dataset consisted of knee (n = 66) and hip (n = 47) OA patients assigned for total joint replacement at Lund University Hospital undergoing pre-operative neuromuscular exercise and 43 matched controls. Sensitivity to pressure pain was assessed by pressure algometry at 10 sites. Subjects were then instructed to perform a standardized static knee extension. Pressure pain thresholds (PPTs) were assessed at the contracting quadriceps muscle (Q) and at the resting deltoid muscle (D) before and during contraction. The relative increase in PPTs during contraction was taken as a measure of localized (Q) or generalized (D) EIA. Patients were assessed at baseline, following on average 12 weeks of neuromuscular exercise and 3 months following surgery. We found a normal function of EIA in OA patients at baseline. Previous studies have reported beneficial effects of physical exercise on pain modulation in healthy subjects. However, no treatment effects on EIA were seen in OA patients despite the increase in muscle strength following neuromuscular exercise and reduced pain following surgery. Compared to controls, OA patients had increased pain sensitivity and no beneficial effects on pain sensitivity were seen following treatment. To our knowledge, this is the first study of EIA in OA patients. Despite increased pain sensitivity, OA patients had a normal function of EIA. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Decreased alertness due to sleep loss increases pain sensitivity in mice

PubMed Central

Alexandre, Chloe; Latremoliere, Alban; Ferreira, Ashley; Miracca, Giulia; Yamamoto, Mihoko; Scammell, Thomas E; Woolf, Clifford J

2018-01-01

Extended daytime and nighttime activities are major contributors to the growing sleep deficiency epidemic1,2, as is the high prevalence of sleep disorders like insomnia. The consequences of chronic insufficient sleep for health remain uncertain3. Sleep quality and duration predict presence of pain the next day in healthy subjects4–7, suggesting that sleep disturbances alone may worsen pain, and experimental sleep deprivation in humans supports this claim8,9. We demonstrate that sleep loss, but not sleep fragmentation, in healthy mice increases sensitivity to noxious stimuli (referred to as ‘pain’) without general sensory hyper-responsiveness. Moderate daily repeated sleep loss leads to a progressive accumulation of sleep debt and also to exaggerated pain responses, both of which are rescued after restoration of normal sleep. Caffeine and modafinil, two wake-promoting agents that have no analgesic activity in rested mice, immediately normalize pain sensitivity in sleep-deprived animals, without affecting sleep debt. The reversibility of mild sleep-loss-induced pain by wake-promoting agents reveals an unsuspected role for alertness in setting pain sensitivity. Clinically, insufficient or poor-quality sleep may worsen pain and this enhanced pain may be reduced not by analgesics, whose effectiveness is reduced, but by increasing alertness or providing better sleep. PMID:28481358

The effect of chemically induced colitis, psychological stress and their combination on visceral pain in female Wistar rats.

PubMed

Deiteren, Annemie; Vermeulen, Wim; Moreels, Tom G; Pelckmans, Paul A; De Man, Joris G; De Winter, Benedicte Y

2014-09-01

Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.

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

PubMed Central

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

2017-01-01

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

Mindfulness Meditation and Cognitive Behavioral Therapy Intervention Reduces Pain Severity and Sensitivity in Opioid-Treated Chronic Low Back Pain: Pilot Findings from a Randomized Controlled Trial

PubMed Central

Burzinski, Cindy A.; Cox, Jennifer; Kloke, John; Stegner, Aaron; Cook, Dane B.; Singles, Janice; Mirgain, Shilagh; Coe, Christopher L.; Bačkonja, Miroslav

2016-01-01

Objective. To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). Design. 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). Setting. Outpatient. Subjects. Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. Methods. The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). Results. Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen’s d = 0.86), and decreased pain sensitivity to thermal stimuli (P < 0.05), without adverse events. Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits. Conclusions. Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP. PMID:26968850

Pain and severe sleep disturbance in the general population: Primary data and meta-analysis from 240,820 people across 45 low- and middle-income countries.

PubMed

Stubbs, Brendon; Vancampfort, Davy; Thompson, Trevor; Veronese, Nicola; Carvalho, Andre F; Solmi, Marco; Mugisha, James; Schofield, Patricia; Matthew Prina, A; Smith, Lee; Koyanagi, Ai

2018-05-22

Pain and sleep disturbances are widespread, and are an important cause of a reduced quality of life. Despite this, there is a paucity of multinational population data assessing the association between pain and sleep problems, particularly among low- and middle-income countries (LMICs). Therefore, we investigated the relationship between pain and severe sleep disturbance across 45 LMICs. Community-based data on 240,820 people recruited via the World Health Survey were analyzed. Multivariable logistic regression analyses adjusted for multiple confounders were performed to quantify the association between pain and severe sleep problems in the last 30 days. A mediation analysis was conducted to explore potential mediators of the relationship between pain and severe sleep disturbance. The prevalence of mild, moderate, severe, and extreme levels of pain was 26.0%, 16.2%, 9.1%, and 2.2% respectively, whilst 7.8% of adults had severe sleep problems. Compared to those with no pain, the odds ratio (OR, 95% CI) for severe sleep problems was 3.65 (3.24-4.11), 9.35 (8.19-10.67) and 16.84 (13.91-20.39) for those with moderate, severe and extreme pain levels respectively. A country wide meta-analysis adjusted for age and sex demonstrated a significant increased OR across all 45 countries. Anxiety, depression and stress sensitivity explained 12.9%, 3.6%, and 5.2%, respectively, of the relationship between pain and severe sleep disturbances. Pain and sleep problems are highly co-morbid across LMICs. Future research is required to better understand this relationship. Moreover, future interventions are required to prevent and manage the pain and sleep disturbance comorbidity. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-05-01

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

Pharmacologic Modulation of Hand Pain in Osteoarthritis: A Double-Blind Placebo-Controlled Functional Magnetic Resonance Imaging Study Using Naproxen

PubMed Central

Sanders, Duncan; Krause, Kristina; O'Muircheartaigh, Jonathan; Thacker, Michael A; Huggins, John P; Vennart, William; Massat, Nathalie J; Choy, Ernest; Williams, Steven C R; Howard, Matthew A

2015-01-01

Objective In an attempt to shed light on management of chronic pain conditions, there has long been a desire to complement behavioral measures of pain perception with measures of underlying brain mechanisms. Using functional magnetic resonance imaging (fMRI), we undertook this study to investigate changes in brain activity following the administration of naproxen or placebo in patients with pain related to osteoarthritis (OA) of the carpometacarpal (CMC) joint. Methods A placebo-controlled, double-blind, 2-period crossover study was performed in 19 individuals with painful OA of the CMC joint of the right hand. Following placebo or naproxen treatment periods, a functionally relevant task was performed, and behavioral measures of the pain experience were collected in identical fMRI examinations. Voxelwise and a priori region of interest analyses were performed to detect between-period differences in brain activity. Results Significant reductions in brain activity following treatment with naproxen, compared to placebo, were observed in brain regions commonly associated with pain perception, including the bilateral primary somatosensory cortex, thalamus, and amygdala. Significant relationships between changes in perceived pain intensity and changes in brain activity were also observed in brain regions previously associated with pain intensity. Conclusion This study demonstrates the sensitivity of fMRI to detect the mechanisms underlying treatments of known efficacy. The data illustrate the enticing potential of fMRI as an adjunct to self-report for detecting early signals of efficacy of novel therapies, both pharmacologic and nonpharmacologic, in small numbers of individuals with persistent pain. PMID:25533872

Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment.

PubMed

Yatagai, Tsuyoshi; Shimauchi, Takatoshi; Yamaguchi, Hayato; Sakabe, Jun-Ichi; Aoshima, Masahiro; Ikeya, Shigeki; Tatsuno, Kazuki; Fujiyama, Toshiharu; Ito, Taisuke; Ojima, Toshiyuki; Tokura, Yoshiki

2018-01-01

Sensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated. To investigate relationship between sensitive skin and AD-associated markers. Forty-two Japanese AD patients and 10 healthy subjects (HS) were enrolled. AD patients were divided into extrinsic (EAD; high IgE levels) and intrinsic (IAD; normal IgE levels) types. We conducted 1% LAST by assessing the four distinct sensations and calculated the frequencies of sensitive skin in EAD, IAD, and HS. We also performed clinical AD-related tests, including transepidermal water loss (TEWL), visual analogue scale (VAS) of pruritus, and quality of life, and measured laboratory markers, including blood levels of IgE, CCL17/TARC, lactate dehydrogenase (LDH) and eosinophil counts, and concentration levels of serum Th1/Th2 cytokines. Filaggrin (FLG) mutations were examined in 21 patients. These values were subjected to correlation analyses with each of the four sensation elements. According to the standard criteria for LAST positivity, the frequencies of LAST-positive subjects were 54.8% and 10.0% in AD and HS, respectively (P=0.014). EAD patients showed a significantly (P=0.026) higher frequency of positive LAST (65.6%) than did IAD patients (20.0%). Among the four LAST sensation elements, the crawly feeling and pain scores positively correlated with VAS of pruritus, total serum IgE, mite-specific IgE, CCL17/TARC, and/or LDH. There was no association of the LAST scores with serum Th1/Th2 cytokine levels. Notably, neither TEWL nor FLG mutations correlated with LAST positivity or any sensation scores. The frequency of sensitive skin is higher in EAD than in IAD. Sensitive skin is associated with AD severity, but not necessarily with barrier condition. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Differential coding of hyperalgesia in the human brain: a functional MRI study.

PubMed

Maihöfner, Christian; Handwerker, Hermann O

2005-12-01

Neuropathic pain can be both ongoing or stimulus-induced. Stimulus-induced pain, also known as hyperalgesia, can be differentiated into primary and secondary hyperalgesia. The former results from sensitization of peripheral nociceptive structures, the latter involves sensitization processes within the central nervous system (CNS). Hypersensitivity towards heat stimuli, i.e. thermal hyperalgesia, is a key feature of primary hyperalgesia, whereas secondary hyperalgesia is characterized by hypersensitivity towards mechanical (e.g. pin-prick) stimulation. Using functional magnetic resonance imaging (fMRI), we investigated if brain activation patterns associated with primary and secondary hyperalgesia might differ. Thermal and pin-prick hyperalgesia were induced on the left forearm in 12 healthy subjects by topical capsaicin (2.5%, 30 min) application. Equal pain intensities of both hyperalgesia types were applied during fMRI experiments, based on previous quantitative sensory testing. Simultaneously, subjects had to rate the unpleasantness of stimulus-related pain. Pin-prick hyperalgesia (i.e. subtraction of brain activations during pin-prick stimulation before and after capsaicin exposure) led to activations of primary and secondary somatosensory cortices (S1 and S2), associative-somatosensory cortices, insula and superior and inferior frontal cortices (SFC, IFC). Brain areas activated during thermal hyperalgesia (i.e. subtraction of brain activations during thermal stimulation before and after capsaicin exposure) were S1 and S2, insula, associative-somatosensory cortices, cingulate cortex (GC), SFC, middle frontal cortex (MFC) and IFC. When compared to pin-prick hyperalgesia, thermal hyperalgesia led to an increased activation of bilateral anterior insular cortices, MFC, GC (Brodmann area 24' and 32') and contralateral SFC and IFC, despite equal pain intensities. Interestingly, stronger activations of GC, contralateral MFC and anterior insula significantly correlated to higher ratings of the stimulus-related unpleasantness. We conclude that thermal and mechanical hyperalgesia produce substantially different brain activation patterns. This is linked to different psychophysical properties.

Spinal Manipulative Therapy Has an Immediate Effect on Thermal Pain Sensitivity in People With Low Back Pain: A Randomized Controlled Trial

PubMed Central

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

2009-01-01

Background Current evidence suggests that spinal manipulative therapy (SMT) is effective in the treatment of people with low back pain (LBP); however, the corresponding mechanisms are unknown. Hypoalgesia is associated with SMT and is suggestive of specific mechanisms. Objective The primary purpose of this study was to assess the immediate effects of SMT on thermal pain perception in people with LBP. A secondary purpose was to determine whether the resulting hypoalgesia was a local effect and whether psychological influences were associated with changes in pain perception. Design This study was a randomized controlled trial. Setting A sample of convenience was recruited from community and outpatient clinics. Participants Thirty-six people (10 men, 26 women) currently experiencing LBP participated in the study. The average age of the participants was 32.39 (SD=12.63) years, and the average duration of LBP was 221.79 (SD=365.37) weeks. Intervention and Measurements Baseline demographic and psychological measurements were obtained, followed by quantitative sensory testing to assess temporal summation and Aδ fiber–mediated pain perception. Next, participants were randomly assigned to ride a stationary bicycle, perform low back extension exercises, or receive SMT. Finally, the same quantitative sensory testing protocol was reassessed to determine the immediate effects of each intervention on thermal pain sensitivity. Results Hypoalgesia to Aδ fiber–mediated pain perception was not observed. Group-dependent hypoalgesia of temporal summation specific to the lumbar innervated region was observed. Pair-wise comparisons indicated significant hypoalgesia in participants who received SMT, but not in those who rode a stationary bicycle or performed low back extension exercises. Psychological factors did not significantly correlate with changes in temporal summation in participants who received SMT. Limitations Only immediate effects of SMT were measured, so the authors are unable to comment on whether the inhibition of temporal summation is a lasting effect. Furthermore, the authors are unable to comment on the relationship between their findings and changes in clinical pain. Conclusions Inhibition of Aδ fiber–mediated pain perception was similar for all groups. However, inhibition of temporal summation was observed only in participants receiving SMT, suggesting a modulation of dorsal horn excitability that was observed primarily in the lumbar innervated area. PMID:19797305

Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study

PubMed Central

Smith, Shad B.; Maixner, Dylan; Greenspan, Joel; Dubner, Ron; Fillingim, Roger; Ohrbach, Richard; Knott, Charles; Slade, Gary; Bair, Eric; Gibson, Dustin G.; Zaykin, Dmitri V.; Weir, Bruce; Maixner, William; Diatchenko, Luda

2011-01-01

Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously-reported associations between TMD and two genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD and they identify potential targets for therapeutic intervention. PMID:22074755

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

PubMed

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

2018-05-01

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

Musculoskeletal sensitization and sleep: chronic muscle pain fragments sleep of mice without altering its duration.

PubMed

Sutton, Blair C; Opp, Mark R

2014-03-01

Musculoskeletal pain in humans is often associated with poor sleep quality. We used a model in which mechanical hypersensitivity was induced by injection of acidified saline into muscle to study the impact of musculoskeletal sensitization on sleep of mice. A one month pre-clinical study was designed to determine the impact of musculoskeletal sensitization on sleep of C57BL/6J mice. We instrumented mice with telemeters to record the electroencephalogram (EEG) and body temperature. We used an established model of musculoskeletal sensitization in which mechanical hypersensitivity was induced using two unilateral injections of acidified saline (pH 4.0). The injections were given into the gastrocnemius muscle and spaced five days apart. EEG and body temperature recordings started prior to injections (baseline) and continued for three weeks after musculoskeletal sensitization was induced by the second injection. Mechanical hypersensitivity was assessed using von Frey filaments at baseline (before any injections) and on days 1, 3, 7, 14, and 21 after the second injection. Mice injected with acidified saline developed bilateral mechanical hypersensitivity at the hind paws as measured by von Frey testing and as compared to control mice and baseline data. Sleep during the light period was fragmented in experimental mice injected with acidified saline, and EEG spectra altered. Musculoskeletal sensitization did not alter the duration of time spent in wakefulness, non-rapid eye movement sleep, or rapid eye movement sleep. Musculoskeletal sensitization in this model results in a distinct sleep phenotype in which sleep is fragmented during the light period, but the overall duration of sleep is not changed. This study suggests the consequences of musculoskeletal pain include sleep disruption, an observation that has been made in the clinical literature but has yet to be studied using preclinical models.

Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely

PubMed Central

Vinall, Jillian; Miller, Steven P.; Synnes, Anne R.; Grunau, Ruth E.

2013-01-01

Children born very preterm (≤32 weeks gestation) show greater internalizing (anxious/depressed) behaviors compared to term-born peers as early as 2 years corrected age (CA), however, the role of early stress in the etiology of internalizing problems in preterm children remains unknown. Therefore, we examined the relationship between neonatal pain and internalizing behavior at 18 months CA in children born very preterm, and examined whether parent behavior and stress moderated this relationship. Participants were 145 children (96 very preterm, 49 full-term) seen at 18 months CA. Neonatal data were obtained from medical and nursing chart review. Neonatal pain was defined as the number of skin-breaking procedures. Cognitive ability was measured using the Bayley Scales of Infant Development-II. Parents completed the Parenting Stress Index-III, Child Behavior Checklist 1.5–5, and participated in a videotaped play session with their child, which was coded using the Emotional Availability Scale-IV. Very preterm children displayed greater Internalizing behaviors compared to full-term controls (P =0.02). Parent Sensitivity and Nonhostility moderated the relationship between neonatal pain and Internalizing behavior (all P <0.05); higher parent education (P <0.03), lower Parenting Stress (P =0.001), and fewer children in the home (P <0.01) were associated with lower Internalizing behavior in very preterm children, after adjusting for neonatal medical confounders, gender and child cognitive ability (all P >0.05). Parent Emotional Availability and stress were not associated with Internalizing behaviors in full-term controls. Positive parent interaction and lower stress appears to ameliorate negative effects of neonatal pain on stress-sensitive behaviors in this vulnerable population. PMID:23748079

The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice.

PubMed

Wang, Weijie; Yu, Yingcong; Li, Jing; Wang, Lin; Li, Zhi; Zhang, Chong; Zhen, Linlin; Ding, Lianshu; Wang, Gang; Sun, Xiaoyang; Xu, Ying

2017-08-01

Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca 2+ /calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca 2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl 2 , ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca 2+ , however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl 2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.

Brain network alterations in the inflammatory soup animal model of migraine.

PubMed

Becerra, Lino; Bishop, James; Barmettler, Gabi; Kainz, Vanessa; Burstein, Rami; Borsook, David

2017-04-01

Advances in our understanding of the human pain experience have shifted much of the focus of pain research from the periphery to the brain. Current hypotheses suggest that the progression of migraine depends on abnormal functioning of neurons in multiple brain regions. Accordingly, we sought to capture functional brain changes induced by the application of an inflammatory cocktail known as inflammatory soup (IS), to the dura mater across multiple brain networks. Specifically, we aimed to determine whether IS alters additional neural networks indirectly related to the primary nociceptive pathways via the spinal cord to the thalamus and cortex. IS comprises an acidic combination of bradykinin, serotonin, histamine and prostaglandin PGE2 and was introduced to basic pain research as a tool to activate and sensitize peripheral nociceptors when studying pathological pain conditions associated with allodynia and hyperalgesia. Using this model of intracranial pain, we found that dural application of IS in awake, fully conscious, rats enhanced thalamic, hypothalamic, hippocampal and somatosensory cortex responses to mechanical stimulation of the face (compared to sham synthetic interstitial fluid administration). Furthermore, resting state MRI data revealed altered functional connectivity in a number of networks previously identified in clinical chronic pain populations. These included the default mode, sensorimotor, interoceptive (Salience) and autonomic networks. The findings suggest that activation and sensitization of meningeal nociceptors by IS can enhance the extent to which the brain processes nociceptive signaling, define new level of modulation of affective and cognitive responses to pain; set new tone for hypothalamic regulation of autonomic outflow to the cranium; and change cerebellar functions. Copyright © 2017. Published by Elsevier B.V.

Brain network alterations in the inflammatory soup animal model of migraine

PubMed Central

Becerra, Lino; Bishop, James; Barmettler, Gabi; Kainz, Vanessa; Burstein, Rami; Borsook, David

2017-01-01

Advances in our understanding of the human pain experience have shifted much of the focus of pain research from the periphery to the brain. Current hypotheses suggest that the progression of migraine depends on abnormal functioning of neurons in multiple brain regions. Accordingly, we sought to capture functional brain changes induced by the application of an inflammatory cocktail known as inflammatory soup (IS), to the dura mater across multiple brain networks. Specifically, we aimed to determine whether IS alters additional neural networks indirectly related to the primary nociceptive pathways via the spinal cord to the thalamus and cortex. IS comprises an acidic combination of bradykinin, serotonin, histamine and prostaglandin PGE2 and was introduced to basic pain research as a tool to activate and sensitize peripheral nociceptors when studying pathological pain conditions associated with allodynia and hyperalgesia. Using this model of intracranial pain, we found that dural application of IS in awake, fully conscious, rats enhanced thalamic, hypothalamic, hippocampal and somatosensory cortex responses to mechanical stimulation of the face (compared to sham synthetic interstitial fluid administration). Furthermore, resting state MRI data revealed altered functional connectivity in a number of networks previously identified in clinical chronic pain populations. These included the default mode, sensorimotor, interoceptive (Salience) and autonomic networks. The findings suggest that activation and sensitization of meningeal nociceptors by IS can enhance the extent to which the brain processes nociceptive signaling, define new level of modulation of affective and cognitive responses to pain; set new tone for hypothalamic regulation of autonomic outflow to the cranium; and change cerebellar functions. PMID:28167076

Fatigue-enhanced hyperalgesia in response to muscle insult: induction and development occur in a sex-dependent manner

PubMed Central

Gregory, N. S.; Gibson-Corley, K.; Frey-Law, L.; Sluka, K. A.

2014-01-01

Chronic muscle pain affects 20–50% of the population, is more common in women than men, and is associated with increased pain during physical activity and exercise. Muscle fatigue is common in people with chronic muscle pain, occurs in response to exercise and is associated with release of fatigue metabolites. Fatigue metabolites can sensitize muscle nociceptors which could enhance pain with exercise. Using a mouse model we tested whether fatigue of a single muscle, induced by electrical stimulation, resulted in enhanced muscle hyperalgesia and if the enhanced hyperalgesia was more pronounced in female mice. Muscle fatigue was induced in combination with a sub-threshold muscle insult (2 injections of pH 5.0 saline) in male and female mice. We show that male and female mice, fatigued immediately prior to muscle insult in the same muscle, develop similar muscle hyperalgesia 24h later. However, female mice also develop hyperalgesia when muscle fatigue and muscle insult occur in different muscles, and when muscle insult is administered 24 hours after fatigue in the same muscle. Further, hyperalgesia lasts significantly longer in females. Finally, muscle insult with or without muscle fatigue results in minimal inflammatory changes in the muscle itself, and sex differences are not related to estradiol (ovariectomy) or changes in brainstem activity (pNR1). Thus, the current model mimics muscle fatigue-induced enhancement of pain observed in chronic muscle pain conditions in the human population. Interactions between fatigue and muscle insult may underlie the development of chronic widespread pain with an associated female predominance observed in human subjects. PMID:23906552

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

PubMed

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

2016-02-26

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

Lubiprostone does not Influence Visceral Pain Thresholds in Patients with Irritable Bowel Syndrome

PubMed Central

Whitehead, William E.; Palsson, Olafur S.; Gangarosa, Lisa; Turner, Marsha; Tucker, Jane

2011-01-01

Background In clinical trials, lubiprostone reduced the severity of abdominal pain. Aims The primary aim was to determine whether lubiprostone raises the threshold for abdominal pain induced by intraluminal balloon distention. A secondary aim was to determine whether changes in pain sensitivity influence clinical pain independently of changes in transit time. Methods Sixty-two patients with irritable bowel syndrome with constipation (IBS-C) participated in an 8-week crossover study. All subjects completed a 14-day baseline ending with a barostat test of pain and urge sensory thresholds. Half, randomly selected, then received 48 ug/day of lubiprostone for 14 days ending with a pain sensitivity test and a Sitzmark test of transit time. This was followed by a 14-day washout and then a crossover to 14 days of placebo with tests of pain sensitivity and transit time. The other half of the subjects received placebo before lubiprostone. All kept symptom diaries. Results Stools were significantly softer when taking lubiprostone compared to placebo (Bristol Stool scores 4.20 vs. 3.44, p<0.001). However, thresholds for pain (17.36 vs. 17.83 mmHg, lubiprostone vs. placebo) and urgency to defecate (14.14 vs. 14.53 mmHg) were not affected by lubiprostone. Transit time was not significantly different between lubiprostone and placebo (51.27 vs. 51.81 hours), and neither pain sensitivity nor transit time was a significant predictor of clinical pain. Conclusions Lubiprostone has no effect on visceral sensory thresholds. The reductions in clinical pain that occur while taking lubiprostone appear to be secondary to changes in stool consistency. PMID:21914041

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

PubMed Central

Sutton, Blair C.; Opp, Mark R.

2014-01-01

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

A sleeping phantom leg awakened following hemicolectomy, thrombosis, and chemotherapy: a case report.

PubMed

Giummarra, Melita J; Bradshaw, John L; Nicholls, Michael Er; Georgiou-Karistianis, Nellie; Gibson, Stephen J

2011-05-25

We describe the case of a patient who experienced phantom pain that began 42 years after right above-the-knee amputation. Immediately prior to phantom pain onset, this long-term amputee had experienced, in rapid succession, cancer, hemicolectomy, chemotherapy, and thrombotic occlusion. Very little has been published to date on the association between chemotherapy and exacerbation of neuropathic pain in amputees, let alone the phenomenon of bringing about pain in amputees who have been pain-free for many decades. While this patient presented with a unique profile following a rare sequence of medical events, his case should be recognized considering the frequent co-occurrence of osteomyelitis, chemotherapy, and amputation. A 68-year-old Australian Caucasian man presented 42 years after right above-the-knee amputation with phantom pain immediately following hemicolectomy, thrombotic occlusion in the amputated leg, and chemotherapy treatment with leucovorin and 5-fluorouracil. He exhibited probable hyperalgesia with a reduced pinprick threshold and increased stump sensitivity, indicating likely peripheral and central sensitization. Our patient, who had long-term nerve injury due to amputation, together with recent ischemic nerve and tissue injury due to thrombosis, exhibited likely chemotherapy-induced neuropathy. While he presented with unique treatment needs, cases such as this one may actually be quite common considering that osteosarcoma can frequently lead to amputation and be followed by chemotherapy. The increased susceptibility of amputees to developing potentially intractable chemotherapy-induced neuropathic pain should be taken into consideration throughout the course of chemotherapy treatment. Patients in whom chronic phantom pain then develops, perhaps together with mobility issues, inevitably place greater demands on healthcare service providers that require treatment by various clinical specialists, including oncologists, neurologists, prosthetists, and, most frequently, general practitioners.

The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia

PubMed Central

2011-01-01

Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids). PMID:21542893

Point-of-care Ultrasound for Nonangulated Distal Forearm Fractures in Children: Test Performance Characteristics and Patient-centered Outcomes.

PubMed

Poonai, Naveen; Myslik, Frank; Joubert, Gary; Fan, Josiah; Misir, Amita; Istasy, Victor; Columbus, Melanie; Soegtrop, Robert; Goldfarb, Alex; Thompson, Drew; Dubrovsky, Alexander Sasha

2017-05-01

Distal forearm fractures are the most common fracture type in children. Point-of-care-ultrasound (POCUS) is increasingly being used, and preliminary studies suggest that it offers an accurate approach to diagnosis. However, outcomes such as pain, satisfaction, and procedure duration have not been explored but may be salient to the widespread acceptance of this technology by caregivers and children. Our objectives were to examine the test performance characteristics of POCUS for nonangulated distal forearm injuries in children and compare POCUS to x-ray with respect to pain, caregiver satisfaction, and procedure duration. We conducted a cross-sectional study involving children aged 4-17 years with a suspected nonangulated distal forearm fracture. Participants underwent both x-ray and POCUS assessment. The primary outcome was sensitivity between POCUS and x-ray, the reference standard. Secondary outcomes included self-reported pain using the Faces Pain Scale-Revised, caregiver satisfaction using a five-item Likert scale, and procedure duration. POCUS was performed in 169 children of whom 76 were diagnosed with a fracture including 61 buckle fractures. Sensitivity of POCUS for distal forearm fractures was 94.7% (95% confidence interval [CI] = 89.7-99.8) and specificity was 93.5% (95% CI = 88.6-98.5). POCUS was associated with a significantly lower median (interquartile range [IQR]) pain score compared to x-ray: 1 (0-2) versus 2 (1-3), respectively (median difference = 0.5; 95% CI = 0.5-1; p < 0.001) and no significant difference in median (IQR) caregiver satisfaction score: 5 (0) versus 5 (4-5), respectively (median difference = 0, 95% CI = 0, p = 1.0). POCUS was associated with a significantly lower median (IQR) procedure duration versus x-ray: 1.5 (0.8-2.2) minutes versus 27 (15-58) minutes, respectively (median difference = 34.1, 95% CI = 26.8-41.5, p < 0.001). Our findings suggest that POCUS assessment of distal forearm injuries in children is accurate, timely, and associated with low levels of pain and high caregiver satisfaction. © 2016 by the Society for Academic Emergency Medicine.

Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity.

PubMed

Baad-Hansen, L; Cairns, Be; Ernberg, M; Svensson, P

2010-01-01

We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.

ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1981-01-01

The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

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

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

PubMed Central

Habib, Abdella M; Matsuyama, Ayako; Okorokov, Andrei L; Santana-Varela, Sonia; Bras, Jose T; Aloisi, Anna Maria; Emery, Edward C; Bogdanov, Yury D; Follenfant, Maryne; Gossage, Sam J; Gras, Mathilde; Humphrey, Jack; Kolesnikov, Anna; Le Cann, Kim; Li, Shengnan; Minett, Michael S; Pereira, Vanessa; Ponsolles, Clara; Sikandar, Shafaq; Torres, Jesus M; Yamaoka, Kenji; Zhao, Jing; Komine, Yuriko; Yamamori, Tetsuo; Maniatis, Nikolas; Panov, Konstantin I; Houlden, Henry; Ramirez, Juan D; Bennett, David L H; Marsili, Letizia; Bachiocco, Valeria; Wood, John N; Cox, James J

2018-01-01

Abstract Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs. PMID:29253101

Occipital Neuralgia from C2 Cavernous Malformation

PubMed Central

Ha, Sang-woo; Choi, Jin-gyu; Son, Byung-chul

2018-01-01

A unique case is presented of chronic occipital neuralgia (ON) caused by cavernous malformation (CM) in the intramedullary C2 spinal cord and subsequent pain relief and remodeling of allodynic pain following dorsal root rhizotomy. A 53-year-old male presented with a 30-year history of chronic allodynic, paroxysmal lancinating pain in the greater and lesser occipital nerves. Typically, the pain was aggravated with neck extension and head movement. Magnetic resonance imaging showed a CM in the right posterolateral side of the intramedullary C2 cord. Considering potential risks associated with removal of the lesion, intradural C1-3 dorsal root rhizotomy with dentate ligament resection was performed. The paroxysmal lancinating pain of ON was significantly alleviated, and the remodeling of the extent of allodynic pain was noted after C1-3 dorsal root rhizotomy. These changes gradually occurred during the second postoperative month, and this effect was maintained for 24 months postoperatively. Significant reduction in chronic allodynic pain of secondary ON caused by cervicomedullary CM involving central sensitization in the trigeminocervical complex was observed with reduction of irritating, afferent input with C1-C3 dorsal root rhizotomy. PMID:29682056

Occipital Neuralgia from C2 Cavernous Malformation.

PubMed

Ha, Sang-Woo; Choi, Jin-Gyu; Son, Byung-Chul

2018-01-01

A unique case is presented of chronic occipital neuralgia (ON) caused by cavernous malformation (CM) in the intramedullary C2 spinal cord and subsequent pain relief and remodeling of allodynic pain following dorsal root rhizotomy. A 53-year-old male presented with a 30-year history of chronic allodynic, paroxysmal lancinating pain in the greater and lesser occipital nerves. Typically, the pain was aggravated with neck extension and head movement. Magnetic resonance imaging showed a CM in the right posterolateral side of the intramedullary C2 cord. Considering potential risks associated with removal of the lesion, intradural C1-3 dorsal root rhizotomy with dentate ligament resection was performed. The paroxysmal lancinating pain of ON was significantly alleviated, and the remodeling of the extent of allodynic pain was noted after C1-3 dorsal root rhizotomy. These changes gradually occurred during the second postoperative month, and this effect was maintained for 24 months postoperatively. Significant reduction in chronic allodynic pain of secondary ON caused by cervicomedullary CM involving central sensitization in the trigeminocervical complex was observed with reduction of irritating, afferent input with C1-C3 dorsal root rhizotomy.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-09-01

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

Standard analgesics reverse burrowing deficits in a rat CCI model of neuropathic pain, but not in models of type 1 and type 2 diabetes-induced neuropathic pain.

PubMed

Rutten, Kris; Gould, Stacey A; Bryden, Luke; Doods, Henri; Christoph, Thomas; Pekcec, Anton

2018-09-17

Burrowing is a rodent behavior validated as a robust and reproducible outcome measure to infer the global effect of pain in several inflammatory pain models. However, less is known about the effect of analgesics on burrowing in neuropathic pain models and no studies have determined burrowing performance in models of diabetes-associated neuropathic pain. To compare the sensitivity of the burrowing assay in different neuropathic pain models: mononeuropathic pain and diabetic polyneuropathy. Burrowing performance was determined by the amount of substrate left in a hollow tube by rats with chronic constriction injury (CCI). In addition, burrowing performance, locomotion and pain development was assessed in the Zucker diabetic fatty (ZDF) rat model, resembling type-2 diabetes. Efficacy of clinically-active reference drugs (opioids, gabapentin and/or pregabalin) were investigated in these models. Burrowing behavior was additionally assessed in a second model, induced by streptozotocin (STZ) treatment, resembling type-1 diabetes. In the CCI model, moderate but consistent burrowing deficits were observed that persisted over a period of ≥20 days. Systemic administration of morphine, pregabalin and gabapentin reversed this deficit. In contrast, none of the reference drugs improved marked burrowing deficits detected in ZDF rats, and pregabalin did not reverse severe burrowing deficits observed in STZ rats. Burrowing performance cannot necessarily be used as pain-related readout across pain models and largely depends on the model used, at least in models of neuropathy. Specifically, analgesic drug effects might be masked by general diabetes-associated alteration of the animals' well-being, resulting in false negative outcomes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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

Prospective study of iliac crest bone graft harvest site pain and morbidity.

PubMed

Kim, David H; Rhim, Richard; Li, Ling; Martha, Juli; Swaim, Bryan H; Banco, Robert J; Jenis, Louis G; Tromanhauser, Scott G

2009-11-01

Morbidity associated with autologous bone graft harvest is an important factor in determining the utility of expensive alternatives such as recombinant bone morphogenic protein. The most frequently reported complication associated with graft harvest is chronic pain. To prospectively determine the degree of pain and morbidity associated with autologous iliac crest bone graft harvest and its effect on activities of daily living. Prospective observational cohort study. One hundred ten adult patients undergoing elective posterior lumbar spinal fusion surgery involving autologous iliac crest bone graft harvest. Patient self-reported Visual Analog Scale (VAS) scores for pain and a study-specific questionnaire regarding activities of daily living. One hundred ten patients were prospectively enrolled. Postoperative VAS scores (0-100) for harvest site pain were obtained at 6-week, 6- and 12-month follow-up. Patients completed a 12-month questionnaire regarding the persistence of specific symptoms and resulting limitation of specific activities. One hundred four patients were available for 1-year follow-up. Mean VAS pain scores (scale 0-100) at 6 weeks, 6 and 12 months were 22.7 (standard deviation [SD], 25.9), 15.9 (SD, 21.5), and 16.1 (SD, 24.6), respectively. At 12 months, 16.5% reported more severe pain from the harvest site than the primary surgical site, 29.1% reported numbness, and 11.3% found the degree of numbness bothersome, whereas 3.9% were bothered by scar appearance. With respect to activity limitations resulting from harvest site pain at 1 year, 15.1% reported some difficulty walking, 5.2% with employment, 12.9% with recreation, 14.1% with household chores, 7.6% with sexual activity, and 5.9% irritation from clothing. There is a significant rate of persistent pain and morbidity from iliac crest bone graft harvest when associated with elective spine surgery. Mean pain scores progressively decline over the first postoperative year. Nevertheless, harvest site pain remains functionally limiting in a significant percentage of patients 1 year after surgery. Rates of functional limitation are higher than previously reported and may be because of increased sensitivity of the prospective study design and targeted investigation of these specific symptoms. Validity of these findings is necessarily limited by patient ability to discriminate harvest site pain from alternative sources of back and buttock pain.

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study.

PubMed

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas known to reflect the ongoing pain experience.

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study

PubMed Central

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas known to reflect the ongoing pain experience. PMID:27486748

A nontoxic pain killer designed by modeling of pathological receptor conformations.

PubMed

Spahn, V; Del Vecchio, G; Labuz, D; Rodriguez-Gaztelumendi, A; Massaly, N; Temp, J; Durmaz, V; Sabri, P; Reidelbach, M; Machelska, H; Weber, M; Stein, C

2017-03-03

Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3',5'-monophosphate inhibition in vitro . It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential. Copyright © 2017, American Association for the Advancement of Science.

Differential Efficacy of Ketamine in the Acute versus Chronic Stages of Complex Regional Pain Syndrome in Mice

PubMed Central

Tajerian, Maral; Leu, David; Yang, Phillip; Huang, Ting Ting; Kingery, Wade S; Clark, J David

2015-01-01

Background Complex regional pain syndrome (CRPS) is a painful, disabling and often chronic condition, where many patients transition from an acute phase with prominent peripheral neurogenic inflammation to a chronic phase with evident central nervous system (CNS) changes. Ketamine is a centrally-acting agent believed to work through blockade of N-methyl-D-aspartate (NMDA) receptors and is being increasingly used for the treatment of refractory CRPS, although the basis for the drug’s effects and efficacy at different stages of the syndrome remain unclear. Methods We used a mouse model of CRPS (n=8–12/group) involving tibia fracture/cast immobilization to test the efficacy of ketamine (2 mg/kg/day; 7 days) or vehicle infusion during acute (3weeks [3w] post-fracture) and chronic (7w post-fracture) stages. Results Acute phase fracture mice displayed elevated limb temperature, edema and nociceptive sensitization that were not reduced by ketamine. Fracture mice treated with ketamine during the chronic phase showed reduced nociceptive sensitization that persisted beyond completion of the infusion. During this chronic phase, ketamine also reduced latent nociceptive sensitization and improved motor function at 18 weeks post-fracture. No side effects of the infusions were identified. These behavioral changes were associated with altered spinal astrocyte activation and expression of pain-related proteins including NMDA receptor 2b (NR2b), Ca2+/calmodulin-dependent protein kinase ii (CaMK2), and brain-derived neurotrophic factor (BNDF). Conclusions Collectively, these results demonstrate that ketamine is efficacious in the chronic, but not acute stages of CRPS, suggesting that the centrally-acting drug is relatively ineffective in early CRPS when peripheral mechanisms are more critical for supporting nociceptive sensitization. PMID:26492479

Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity.

PubMed

Zhang, L P; Kline, R H; Deevska, G; Ma, F; Nikolova-Karakashian, M; Westlund, K N

2015-12-17

The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of transient receptor potential cation channel subfamily V member 4 (TRPV4) in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF)-induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF-induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF-induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted μ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A systematic review of cross-cultural comparison studies of child, parent, and health professional outcomes associated with pediatric medical procedures.

PubMed

Kristjánsdóttir, Olöf; Unruh, Anita M; McAlpine, Linda; McGrath, Patrick J

2012-03-01

The purpose of this review was to evaluate systematically all published and unpublished research concerning culture and medical procedural pain in children. Databases, reference lists, and electronic list servers were searched as data sources. Fifteen studies met the inclusion criteria. Most studies (80%) were conducted solely in the United States comparing Caucasian American groups to other local subculture(s) (ie, African American, Hispanic, or Japanese). The studies compared, cross culturally, pediatric pain-related outcomes in children, parents and/or health professionals. The medical procedural experiences included surgery, immunization, spinal tap, bone marrow aspiration, needle procedures, orthopedic, and wound-related injuries. The evidence published to date suggests that cultural factors may be associated with children's pain experiences when elicited by medical procedural pain, specifically children's pain behavior. Nevertheless, research using more sophisticated research methods is needed to develop culturally sensitive behavioral pain measures. Measures that include physiological pain parameters in addition to other behavioral outcomes may be helpful. Culturally comparative research would benefit from the use of theoretical frameworks to advance our understanding of the cultural underpinnings of child pain development and guide future research. The current evidence supports that children and parents belonging to cultural minority groups, and in need of health care, are a vulnerable population. Together, researchers and clinicians are encouraged to explore this understudied area, and take advantage of sophisticated methods developed by disciplines like cross-cultural psychology. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

[Pain and analgesia : Mutations of voltage-gated sodium channels].

PubMed

Eberhardt, M J; Leffler, A

2017-02-01

Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav1.8 and Nav1.9. A specific role for the function of nociceptive neurons was postulated for each. Whereas no selective sodium channel inhibitors have been established in the clinic so far, the relevance of all three isoforms regarding the pain sensitivity in humans is currently undergoing a remarkable verification through the translation of preclinical data into clinically manifest pictures. For the last ten years, Nav1.7 has been the main focus of clinical interest, as a large number of hereditary mutants were identified. The so-called "gain-of-function" mutations of Nav1.7 cause the pain syndromes hereditary erythromelalgia and paroxysmal extreme pain disorder. In addition, several Nav1.7 mutants were shown to be associated with small-fiber neuropathies. On the contrary, "loss-of-function" Nav1.7 mutants lead to a congenital insensitivity to pain. Recently, several gain-of-function mutations in Nav1.8 and Nav1.9 have been identified in patients suffering from painful peripheral neuropathies. However, another gain-of-function Nav1.9 mutation is associated with congenital insensitivity to pain. This review offers an overview of published work on painful Nav mutations with clinical relevance, and proposes possible consequences for the therapy of different pain symptoms resulting from these findings.

Relationship of Corneal Pain Sensitivity With Dry Eye Symptoms in Dry Eye With Short Tear Break-Up Time.

PubMed

Kaido, Minako; Kawashima, Motoko; Ishida, Reiko; Tsubota, Kazuo

2016-03-01

The purpose of this prospective comparative study was to investigate corneal sensitivity in subjects with unstable tear film, with and without dry eye (DE) symptoms. Forty-one eyes of 41 volunteers (mean age: 45.1 ± 9.4 years; age range, 23-57 years), with normal tear function and ocular surface except for tear stability, were studied. The eyes were divided into two groups depending on the presence or absence of DE symptoms: 21 eyes with DE symptoms (symptomatic group); and 20 eyes without DE symptoms (asymptomatic group). Three types of corneal sensitivity values were measured using a Cochet-Bonnet esthesiometer: the sensitivity for perception of touch (S-touch), the sensitivity for blinking (S-blink), and the sensitivity for pain (S-pain). Mean S-blink and S-pain were significantly higher in the symptomatic group than in the asymptomatic group (P < 0.05), whereas there was no significant difference in mean S-touch between these groups (P > 0.05). Corneal sensitivity for blinking and pain evoked by increased stimuli was higher in the symptomatic group (subjects with short break-up time DE) compared with subjects who have no DE symptoms despite decreased tear stability. The presence of both tear instability and hyperesthesia, rather than tear instability alone, may contribute to DE pathogenesis.

Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity.

PubMed

Filho, F L A; Macedo, G M; Dos Santos, A A; Rodrigues, L V; Oliveira, R B; Nobre E Souza, M A

2011-02-01

Stapled haemorrhoidopexy may damage the anorectal musculature and its sensorimotor function. Most studies have not used a barostat for the measurement of compliance. This study aimed to investigate the effect of stapled haemorrhoidopexy on rectal compliance and sensitivity. After Ethical Committee approval, we studied 10 male patients (mean age 33.8 years) with third- or fourth-degree haemorrhoids. Rectal compliance and sensitivity were measured with a 600-ml bag and an electronic barostat. Volunteers were submitted to two consecutive rectal distension protocols, including continuous distension at 2, 4 and 6 months after stapled haemorrhoidopexy. Intraluminal volume and pressure were recorded, including the first rectal sensation, desire to defecate and onset of rectal pain. Another group of 10 male control patients (mean age 24.9 years) with pilonidal sinus and no haemorrhoids was also included in the study. Two months after stapled haemorrhoidopexy, rectal compliance decreased (7.1 ± 0.2 vs 5.3 ± 0.1, 6.4 ± 0.1 vs 5.1 ± 0.1 and 5.6 ± 0.2 vs 4.7 ± 0.1 ml/mmHg for first rectal sensation, desire to defecate and rectal pain, respectively; P < 0.05). The sensitivity threshold volume did not change for the first sensation but decreased significantly for the desier to defecate and pain (p <0.05) (116.8 ± 13.8 vs 148.4 ± 14.61, 251.1 ± 8.9 vs 185.8 ± 8.6 and 293.3 ± 16.6 vs 221.2 ± 6.0 ml for first rectal sensation, desire to defecate and rectal pain, respectively). Four and 6 months after surgery, rectal compliance and sensitivity returned to levels similar to those in the basal period. Muscle tissue was found in only three of the 10 resected doughnuts. Controls remained without any change in rectal compliance and sensitivity. Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity threshold in young male patients. © 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.

Short-term changes in neck pain, widespread pressure pain sensitivity, and cervical range of motion after the application of trigger point dry needling in patients with acute mechanical neck pain: a randomized clinical trial.

PubMed

Mejuto-Vázquez, María J; Salom-Moreno, Jaime; Ortega-Santiago, Ricardo; Truyols-Domínguez, Sebastián; Fernández-de-Las-Peñas, César

2014-04-01

Randomized clinical trial. To determine the effects of trigger point dry needling (TrPDN) on neck pain, widespread pressure pain sensitivity, and cervical range of motion in patients with acute mechanical neck pain and active trigger points in the upper trapezius muscle. TrPDN seems to be effective for decreasing pain in individuals with upper-quadrant pain syndromes. Potential effects of TrPDN for decreasing pain and sensitization in individuals with acute mechanical neck pain are needed. Methods Seventeen patients (53% female) were randomly assigned to 1 of 2 groups: a single session of TrPDN or no intervention (waiting list). Pressure pain thresholds over the C5-6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle; neck pain intensity; and cervical spine range-of-motion data were collected at baseline (pretreatment) and 10 minutes and 1 week after the intervention by an assessor blinded to the treatment allocation of the patient. Mixed-model analyses of variance were used to examine the effects of treatment on each outcome variable. Patients treated with 1 session of TrPDN experienced greater decreases in neck pain, greater increases in pressure pain threshold, and higher increases in cervical range of motion than those who did not receive an intervention at both 10 minutes and 1 week after the intervention (P<.01 for all comparisons). Between-group effect sizes were medium to large immediately after the TrPDN session (standardized mean score differences greater than 0.56) and large at the 1-week follow-up (standardized mean score differences greater than 1.34). The results of the current randomized clinical trial suggest that a single session of TrPDN may decrease neck pain intensity and widespread pressure pain sensitivity, and also increase active cervical range of motion, in patients with acute mechanical neck pain. Changes in pain, pressure pain threshold, and cervical range of motion surpassed their respective minimal detectable change values, supporting clinically relevant treatment effects. Level of Evidence Therapy, level 1b-.

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

PubMed Central

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

2016-01-01

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

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

PubMed Central

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

2008-01-01

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

An Integrative Neuroscience Framework for the Treatment of Chronic Pain: From Cellular Alterations to Behavior.

PubMed

Greenwald, Jess D; Shafritz, Keith M

2018-01-01

Chronic pain can result from many pain syndromes including complex regional pain syndrome (CRPS), phantom limb pain and chronic low back pain, among others. On a molecular level, chronic pain syndromes arise from hypersensitization within the dorsal horn of the spinal cord, a process known as central sensitization. Central sensitization involves an upregulation of ionotropic and metabotropic glutamate receptors (mGluRs) similar to that of long-term potentiation (LTP). Regions of the brain in which LTP occurs, such as the amygdala and hippocampus, are implicated in fear- and memory-related brain circuity. Chronic pain dramatically influences patient quality of life. Individuals with chronic pain may develop pain-related anxiety and pain-related fear. The syndrome also alters functional connectivity in the default-mode network (DMN) and salience network. On a cellular/molecular level, central sensitization may be reversed through degradative glutamate receptor pathways. This, however, rarely happens. Instead, cortical brain regions may serve in a top-down regulatory capacity for the maintenance or alleviation of pain. Specifically, the medial prefrontal cortex (mPFC), which plays a critical role in fear-related brain circuits, the DMN, and salience network may be the driving forces in this process. On a cellular level, the mPFC may form new neural circuits through LTP that may cause extinction of pre-existing pain pathways found within fear-related brain circuits, the DMN, and salience network. In order to promote new LTP connections between the mPFC and other key brain structures, such as the amygdala and insula, we propose a holistic rehabilitation program including cognitive behavioral therapy (CBT) and revolving around: (1) cognitive reappraisals; (2) mindfulness meditation; and (3) functional rehabilitation. Unlike current medical interventions focusing upon pain-relieving medications, we do not believe that chronic pain treatment should focus on reversing the effects of central sensitization. Instead, we propose here that it is critical to focus on non-invasive efforts to promote new neural circuits originating from the mPFC.

Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

PubMed

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

2016-03-01

Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest that central sensitization and neuropathic features contribute to NSAID-resistant ongoing OA joint pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Initial accuracy assessment of the modified S-LANSS for the detection of neuropathic orofacial pain conditions.

PubMed

Herrero Babiloni, Alberto; Nixdorf, Donald R; Law, Alan S; Moana-Filho, Estephan J; Shueb, Sarah S; Nguyen, Ruby H; Durham, Justin

2017-01-01

To evaluate the accuracy of a questionnaire modified for the identification of intraoral pain with neuropathic characteristics in a clinical orofacial pain sample population. 136 participants with at least one of four orofacial pain diagnoses (temporomandibular disorders [TMD, n = 41], acute dental pain [ADP, n = 41], trigeminal neuralgia [TN, n = 19], persistent dentoalveolar pain disorder [PDAP, n = 14]) and a group of pain-free controls (n = 21) completed the modified S-LANSS, a previously adapted version of the original questionnaire devised to detected patients suffering from intraoral pain with neuropathic characteristics. Psychometric properties (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) were calculated in two analyses with two different thresholds: (1) Detection of pain with neuropathic characteristics: PDAP + TN were considered positive, and TMD + ADP + controls were considered negative per gold standard (expert opinion). (2) Detection of PDAP: PDAP was considered positive and TMD + ADP were considered negative per gold standard. For both analyses, target values for adequate sensitivity and specificity were defined as ≥ 80%. For detection of orofacial pain with neuropathic characteristics (PDAP + TN), the modified S-LANSS presented with the most optimistic threshold sensitivity of 52% (95% confidence interval [CI], 34-69), specificity of 70% (95% CI, 60-79), PPV of 35% (95% CI, 22-51), and NPV of 82% (95% CI, 72-89). For detection of PDAP only, with the most optimistic threshold sensitivity was 64% (95% CI, 35-87), specificity 63% (95% CI, 52-74), PPV 23% (95% CI, 11-39) and NPV 91% (95% CI, 81-97). Based on a priori defined criteria, the modified S-LANSS did not show adequate accuracy to detect intraoral pain with neuropathic characteristics in a clinical orofacial pain sample.

The effect of culture on pain sensitivity.

PubMed

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

2016-02-01

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

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

PubMed

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

2011-10-01

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

Examining the mediational role of psychological flexibility, pain catastrophizing, and visceral sensitivity in the relationship between psychological distress, irritable bowel symptom frequency, and quality of life.

PubMed

Cassar, G E; Knowles, S; Youssef, G J; Moulding, R; Uiterwijk, D; Waters, L; Austin, D W

2018-06-08

The aim of the current study was to use Structural Equation Modelling (SEM) to examine whether psychological flexibility (i.e. mindfulness, acceptance, valued-living) mediates the relationship between distress, irritable bowel syndrome (IBS) symptom frequency, and quality of life (QoL). Ninety-two individuals participated in the study (12 male, 80 female, M age  = 36.24) by completing an online survey including measures of visceral sensitivity, distress, IBS-related QoL, mindfulness, bowel symptoms, pain catastrophizing, acceptance, and valued-living. A final model with excellent fit was identified. Psychological distress significantly and directly predicted pain catastrophizing, valued-living, and IBS symptom frequency. Pain catastrophizing directly predicted visceral sensitivity and acceptance, while visceral sensitivity significantly and directly predicted IBS symptom frequency and QoL. Symptom frequency also had a direct and significant relationship with QoL. The current findings suggest that interventions designed to address unhelpful cognitive processes related to visceral sensitivity, pain catastrophizing, and psychological distress may be of most benefit to IBS-related QoL.

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

PubMed

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

2017-10-01

Context insensitivity has been put forward as a potential mechanism explaining the high co-occurrence of pain and emotional distress. In the pain literature, the concept has only been introduced at a theoretical level and an assessment tool for exploring its impact is lacking. In an interpersonal setting, a core aspect of context sensitivity and insensitivity concerns when to disclose and when to avoid expressing pain and related distress. Both context insensitive disclosure and context insensitive avoidance may hamper interpersonal support and fuel the problem. This exploratory study describes an attempt to develop a self-report instrument to assess tendencies to disclose vs. avoid expressions of pain and related distress, as well as self-perceived adjustment of disclosure vs. avoidance to the context. A pool of items was systematically developed to assess different aspects of context insensitivity, including disclosure vs. avoidance of expression. 105 participants with persistent pain were recruited at pain rehabilitation clinics (80% of the sample) and in a university setting (20% of the sample). The participants responded to the pool of items as well as to a number of validated self-report instruments covering pain, pain-related disability, pain catastrophizing, emotion regulation tendencies, self-compassion and pain acceptance. The analyses explored the factorial structure of the initial instrument, as well as the criterion and construct validity. The analyses confirmed a stable underlying structure of the initial scale, with four distinct factors explaining 64.4% of the total variance. However, the criterion and construct validity could only be confirmed for one of the factors, which contained items reflecting context insensitive avoidance of expression. Consequently, only this factor, demonstrating very good internal consistency, was kept in the final version of the instrument which was named context insensitive avoidance (CIA). We found support for the final version of our instrument, capturing one prominent aspect of context insensitivity. Avoidance of expression was related to higher ratings of pain, disability, catastrophizing and suppression as well as to lower levels of self-compassion. We encourage further studies to explore the impact of context insensitive avoidance for regulating pain and associated negative emotions. Yet, more research is needed that goes beyond self-report and includes other aspects of context. It is urgent to develop systematic ways for assessing context insensitivity, as it will enhance our understanding of regulatory strategies as potential transdiagnostic mechanisms in pain and emotion. This tool for assessing contextually insensitive avoidance of expression could potentially be used both clinically and in future research to advance our understanding of comorbid problems with pain and emotional distress. Further research is needed to develop methods for assessing other aspects of context insensitivity to fully understand its impact in patients suffering from pain. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations.

PubMed

Dworkin, Robert H; Turk, Dennis C; Peirce-Sandner, Sarah; Baron, Ralf; Bellamy, Nicholas; Burke, Laurie B; Chappell, Amy; Chartier, Kevin; Cleeland, Charles S; Costello, Ann; Cowan, Penney; Dimitrova, Rozalina; Ellenberg, Susan; Farrar, John T; French, Jacqueline A; Gilron, Ian; Hertz, Sharon; Jadad, Alejandro R; Jay, Gary W; Kalliomäki, Jarkko; Katz, Nathaniel P; Kerns, Robert D; Manning, Donald C; McDermott, Michael P; McGrath, Patrick J; Narayana, Arvind; Porter, Linda; Quessy, Steve; Rappaport, Bob A; Rauschkolb, Christine; Reeve, Bryce B; Rhodes, Thomas; Sampaio, Cristina; Simpson, David M; Stauffer, Joseph W; Stucki, Gerold; Tobias, Jeffrey; White, Richard E; Witter, James

2010-05-01

There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain. Copyright 2010 International Association for the Study of Pain. All rights reserved.

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

PubMed Central

Taherianfard, Mahnaz; Mosavi, Mahnaz

2011-01-01

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

Facial affect processing in patients receiving opioid treatment in palliative care: preferential processing of threat in pain catastrophizers.

PubMed

Carroll, Erin M A; Kamboj, Sunjeev K; Conroy, Laura; Tookman, Adrian; Williams, Amanda C de C; Jones, Louise; Morgan, Celia J A; Curran, H Valerie

2011-06-01

As a multidimensional phenomenon, pain is influenced by various psychological factors. One such factor is catastrophizing, which is associated with higher pain intensity and emotional distress in cancer and noncancer pain. One possibility is that catastrophizing represents a general cognitive style that preferentially supports the processing of negative affective stimuli. Such preferential processing of threat--toward negative facial expressions, for example--is seen in emotional disorders and is sensitive to pharmacological treatment. Whether pharmacological (analgesic) treatment might also influence the processing of threat in pain patients is currently unclear. This study investigates the effects catastrophizing on processing of facial affect in those receiving an acute opioid dose. In a double-blind crossover design, the performance of 20 palliative care patients after their usual dose of immediate-release opioid was compared with their performance following matched-placebo administration on a facial affect recognition (i.e., speed and accuracy) and threat-pain estimation task (i.e., ratings of pain intensity). The influence of catastrophizing was examined by splitting the sample according to their score on the Pain Catastrophizing Scale (PCS). Opioid administration had no effect on facial affect processing compared with placebo. However, the main finding was that enhanced processing of fear, sadness, and disgust was found only in patients who scored highly on the PCS. There was no difference in performance between the two PCS groups on the other emotions (i.e., happiness, surprise, and anger). These findings suggest that catastrophizing is associated with an affective information-processing bias in patients with severe pain conditions. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Ablating spinal NK1-bearing neurons eliminates the development of pain & reduces spinal neuronal hyperexcitability & inflammation from mechanical joint injury in the rat

PubMed Central

Weisshaar, Christine L.; Winkelstein, Beth A.

2014-01-01

The facet joint is a common source of pain especially from mechanical injury. Although chronic pain is associated with altered spinal glial and neuronal responses, the contribution of specific spinal cells to joint pain are not understood. This study used the neurotoxin [Sar9,Met(O2)11]-substance P-saporin (SSP-SAP) to selectively eliminate spinal cells expressing neurokinin-1 receptor (NK1R) in a rat model of painful facet joint injury to determine the role of those spinal neurons in pain from facet injury. Following spinal administration of SSP-SAP or its control (blank-SAP), a cervical facet injury was imposed and behavioral sensitivity assessed. Spinal extracellular recordings were made on day 7 to classify neurons and quantify evoked firing. Spinal glial activation and IL1α expression also were evaluated. SSP-SAP prevented the development of mechanical hyperalgesia that is induced by joint injury and reduced NK1R expression and mechanically-evoked neuronal firing in the dorsal horn. SSP-SAP also prevented a shift toward wide dynamic range neurons that is seen after injury. Spinal astrocytic activation and IL1α expression were reduced to sham levels with SSP-SAP treatment. These results suggest that spinal NK1R-bearing cells are critical in initiating spinal nociception and inflammation associated with a painful mechanical joint injury. Perspective Results demonstrate that cells expressing NK1R in the spinal cord are critical for the development of joint pain and spinal neuroplasticity and inflammation after trauma to the joint. These findings have utility for understanding mechanisms of joint pain and developing potential targets to treat pain. PMID:24389017

Parathyroid Hormone-Related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity

PubMed Central

Shepherd, Andrew J.; Mickle, Aaron D.; Kadunganattil, Suraj; Hu, Hongzhen; Mohapatra, Durga P.

2018-01-01

Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment. Previous studies have suggested that PTHrP could sensitize nociceptive sensory neurons, resulting in peripheral pain hypersensitivity. In this study, we found that PTHrP induces both heat and mechanical hypersensitivity, that are dependent on the pain-transducing transient receptor potential channel family vanilloid, member-1 (TRPV1), but not the mechano-transducing TRPV4 and TRPA1 ion channels. Functional ratiometric Ca2+ imaging and voltage-clamp electrophysiological analysis of cultured mouse DRG neurons show significant potentiation of TRPV1, but not TRPA1 or TRPV4 channel activation by PTHrP. Interestingly, PTHrP exposure led to the slow and sustained activation of TRPV1, in the absence of any exogenous channel agonist, and is dependent on the expression of the type-1 parathyroid hormone receptor (PTH1), as well as on downstream phosphorylation of the channel by protein kinase C (PKC). Accordingly, local administration of specific small-molecule antagonists of TRPV1 to mouse hindpaws after the development of PTHrP-induced mechanical hypersensitivity led to its significant attenuation. Collectively, our findings suggest that PTHrP/PTH1-mediated flow activation of TRPV1 channel contributes at least in part to the development and maintenance of peripheral mechanical pain hypersensitivity, and could therefore constitute a mechanism for nociceptor sensitization in the context of metastatic bone cancer pain. PMID:29497363

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 ...

Evolutionary considerations in the development of chronic pelvic pain.

PubMed

Jarrell, John; Arendt-Nielsen, Lars

2016-08-01

Chronic pelvic pain is common among women of reproductive age and is associated with significant morbidity and comorbidities. In this Viewpoint, we explore the evolutionary cause of pelvic pain and summarize evidence that supports a menstruation-related evolutionary cause of chronic visceral pelvic pain: (1) lifetime menstruation has increased; (2) severe dysmenorrhea is common in the chronic pelvic pain population, particularly among those with pain sensitization; and (3) a potential biological mechanism can be identified. Thus, chronic pelvic pain may arise from the mismatch between the slow pace of biological evolution in our bodies and the relatively rapid pace of cultural changes that have resulted in increased menstrual frequency due to earlier menarche, later mortality, and lower fecundity. One possible mechanism that explains the development of persistent pain from repeated episodes of intermittent pain is hyperalgesic priming, a physiological process defined as a long-lasting latent hyperresponsiveness of nociceptors to inflammatory mediators after an inflammatory or neuropathic insult. The repetitive severely painful menstrual episodes may play such a role. From an evolutionary perspective the relatively rapid increase in lifetime menstruation experience in contemporary society may contribute to a mismatch between lifetime menstruation and the physiological pain processes, leading to a maladaptive state of chronic visceral pelvic pain. Our current physiology does not conform to current human needs. Copyright © 2016 Elsevier Inc. All rights reserved.

Minimum clinically important differences in chronic pain vary considerable by baseline pain and methodological factors: systematic review of empirical studies.

PubMed

Frahm Olsen, Mette; Bjerre, Eik; Hansen, Maria Damkjær; Tendal, Britta; Hilden, Jørgen; Hróbjartsson, Asbjørn

2018-05-21

The minimum clinically important difference (MCID) is used to interpret the relevance of treatment effects, e.g., when developing clinical guidelines, evaluating trial results or planning sample sizes. There is currently no agreement on an appropriate MCID in chronic pain and little is known about which contextual factors cause variation. This is a systematic review. We searched PubMed, EMBASE, and Cochrane Library. Eligible studies determined MCID for chronic pain based on a one-dimensional pain scale, a patient-reported transition scale of perceived improvement, and either a mean change analysis (mean difference in pain among minimally improved patients) or a threshold analysis (pain reduction associated with best sensitivity and specificity for identifying minimally improved patients). Main results were descriptively summarized due to considerable heterogeneity, which were quantified using meta-analyses and explored using subgroup analyses and metaregression. We included 66 studies (31.254 patients). Median absolute MCID was 23 mm on a 0-100 mm scale (interquartile range [IQR] 12-39) and median relative MCID was 34% (IQR 22-45) among studies using the mean change approach. In both cases, heterogeneity was very high: absolute MCID I 2  = 99% and relative MCID I 2  = 96%. High variation was also seen among studies using the threshold approach: median absolute MCID was 20 mm (IQR 15-30) and relative MCID was 32% (IQR 15-41). Absolute MCID was strongly associated with baseline pain, explaining approximately two-thirds of the variation, and to a lesser degree with the operational definition of minimum pain relief and clinical condition. A total of 15 clinical and methodological factors were assessed as possible causes for variation in MCID. MCID for chronic pain relief vary considerably. Baseline pain is strongly associated with absolute, but not relative, measures. To a much lesser degree, MCID is also influenced by the operational definition of relevant pain relief and possibly by clinical condition. Explicit and conscientious reflections on the choice of an MCID are required when classifying effect sizes as clinically important or trivial. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical Phenotype Classifications Based on Static Varus Alignment and Varus Thrust in Japanese Patients With Medial Knee Osteoarthritis

PubMed Central

Iijima, Hirotaka; Fukutani, Naoto; Fukumoto, Takahiko; Uritani, Daisuke; Kaneda, Eishi; Ota, Kazuo; Kuroki, Hiroshi; Matsuda, Shuichi

2015-01-01

Objective To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods Patients in an orthopedic clinic (n = 266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n = 173), dynamic varus (n = 17), static varus (n = 50), and static varus + dynamic varus (n = 26). The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08–12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19–320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. PMID:26017348

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

PubMed

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

2013-07-01

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

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

PubMed

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

2016-09-01

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

Intravenous sub-anesthetic ketamine for perioperative analgesia

PubMed Central

Gorlin, Andrew W; Rosenfeld, David M; Ramakrishna, Harish

2016-01-01

Ketamine, an N-methyl-d-aspartate antagonist, blunts central pain sensitization at sub-anesthetic doses (0.3 mg/kg or less) and has been studied extensively as an adjunct for perioperative analgesia. At sub-anesthetic doses, ketamine has a minimal physiologic impact though it is associated with a low incidence of mild psychomimetic symptoms as well as nystagmus and double vision. Contraindications to its use do exist and due to ketamine's metabolism, caution should be exercised in patients with renal or hepatic dysfunction. Sub-anesthetic ketamine improves pain scores and reduces perioperative opioid consumption in a broad range of surgical procedures. In addition, there is evidence that ketamine may be useful in patients with opioid tolerance and for preventing chronic postsurgical pain. PMID:27275042

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.

Effectiveness of manual therapy versus surgery in pain processing due to carpal tunnel syndrome: A randomized clinical trial.

PubMed

Fernández-de-Las-Peñas, C; Cleland, J; Palacios-Ceña, M; Fuensalida-Novo, S; Alonso-Blanco, C; Pareja, J A; Alburquerque-Sendín, F

2017-08-01

People with carpal tunnel syndrome (CTS) exhibit widespread pressure pain and thermal pain hypersensitivity as a manifestation of central sensitization. The aim of our study was to compare the effectiveness of manual therapy versus surgery for improving pain and nociceptive gain processing in people with CTS. The trial was conducted at a local regional Hospital in Madrid, Spain from August 2014 to February 2015. In this randomized parallel-group, blinded, clinical trial, 100 women with CTS were randomly allocated to either manual therapy (n = 50), who received three sessions (once/week) of manual therapies including desensitization manoeuvres of the central nervous system, or surgical intervention (n = 50) group. Outcomes including pressure pain thresholds (PPT), thermal pain thresholds (HPT or CPT), and pain intensity which were assessed at baseline, and 3, 6, 9 and 12 months after the intervention by an assessor unaware of group assignment. Analysis was by intention to treat with mixed ANCOVAs adjusted for baseline scores. At 12 months, 95 women completed the follow-up. Patients receiving manual therapy exhibited higher increases in PPT over the carpal tunnel at 3, 6 and 9 months (all, p < 0.01) and higher decrease of pain intensity at 3 month follow-up (p < 0.001) than those receiving surgery. No significant differences were observed between groups for the remaining outcomes. Manual therapy and surgery have similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with CTS. Neither manual therapy nor surgery resulted in changes in thermal pain sensitivity. The current study found that manual therapy and surgery exhibited similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with carpal tunnel syndrome at medium- and long-term follow-ups investigating changes in nociceptive gain processing after treatment in carpal tunnel syndrome. © 2017 European Pain Federation - EFIC®.

Comparison of Low Back Pain Recovery and Persistence: A Descriptive Study of Characteristics at Pain Onset.

PubMed

Starkweather, Angela R; Lyon, Debra E; Kinser, Patricia; Heineman, Amy; Sturgill, Jamie L; Deng, Xiaoyan; Siangphoe, Umaporn; Elswick, R K; Greenspan, Joel; Dorsey, Susan G

2016-07-01

Persistent low back pain is a significant problem worldwide. Early identification and treatment of individuals at high risk for persistent low back pain have been suggested as strategies to decrease the rate of disability associated with this condition. To examine and compare demographic, pain-related, psychological, and somatosensory characteristics in a cohort of participants with acute low back pain who later went on to experience persistent low back pain or whose pain resolved within the first 6 weeks after initial onset. A descriptive study was conducted among men and women 18-50 years of age who had an acute episode of low back pain. Study questionnaires were administered to collect demographic information and measures of pain, coping, reactivity, mood, work history and satisfaction, and disability. A standardized protocol of quantitative sensory testing was performed on each participant at the painful area of their low back and at a remote site on their arm. The sample consisted of 48 participants, of whom 19 went on to develop persistent low back pain and 29 resolved. Compared to the resolved group, the persistent low back pain group was significantly older and had a lower level of educational attainment, a higher body mass index, and higher mean "least" pain score on the Brief Pain Inventory-Short Form. Significantly higher thermal detection thresholds at the painful and remote sites as well as signs of central sensitivity differentiated the persistent pain group from the resolved group during the acute stage of low back pain. © The Author(s) 2016.

The Physiology of Bone Pain. How Much Do We Really Know?

PubMed Central

Nencini, Sara; Ivanusic, Jason J.

2016-01-01

Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections. PMID:27199772

Pain in Alzheimer's disease: A study of behavior and neural correlates

NASA Astrophysics Data System (ADS)

Beach, Paul Anthony

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by insidious and progressive impairment of cognition, emotion, and memory. Though pain in patients with AD is a major medical concern it is under diagnosed and under treated in patients, compared to cognitively healthy elderly. Further complicating matters, subjective self-report of pain by becomes increasingly compromised with disease progression; this often leaves clinicians and caregivers no choice but to rely on discerning pain from behavior alone. Patients also report pain at a lower frequency and intensity than healthy seniors (HS). These findings, coupled with recognition that AD pathology affects many pain processing brain regions, have prompted examination of whether AD alters pain perception. While there is evidence that AD actually predisposes heightened perception of pain, several issues remain: experimental work is limited to a handful of studies, whose results have been inconsistent; few examinations of pain in AD have included patients with advanced disease; the neural mechanism underlying altered pain in AD is not clear. I addressed these gaps in the literature by examining subjective, behavioral, and autonomic pain responses in 33 HS and 38 patients with varying severities of AD. A subset of these subjects (24 HS and 20 AD) were scanned, using fMRI. I then determined how the functional connectivity of various resting-state networks (RSNs) were associated with measured pain responses. I found that AD patients rated low-level stimuli as more painful than HS. Also, patients, regardless of severity, showed greater degrees of pain behaviors than HS - both with respect to global behaviors as measured by a clinical pain scale and facial responses as measured by an experimental tool. In contrast, autonomic responses were blunted with advancing AD. Altered pain responses in AD were associated with altered function of RSNs involved in attention and internal mentation, affect, somatosensation, and interoception (p<0.05, FWE corrected). These findings provide further evidence and an improved understanding of the neural basis for heightened pain sensitivity in patients with AD. They also emphasize the necessity to improve pain assessment and treatment strategies for a vulnerable patient population set to expand greatly in the coming decades.

Public Reporting of MRI of the Lumbar Spine for Low Back Pain and Changes in Clinical Documentation.

PubMed

Flug, Jonathan A; Lind, Kimberly E

2017-12-01

OP-8 is the Medicare imaging efficiency metric for MRI of the lumbar spine for low back pain in the outpatient hospital. We studied trends in exclusion criteria coding over time by site of service after implementation of OP-8 to evaluate provider's response to public reporting. We conducted a secondary data analysis using the Medicare Limited Data Set 5% sample for beneficiaries with MRI lumbar spine and lower back pain during 2009 to 2014. We evaluated the association between excluding condition prevalence and site by using generalized estimating equations regression. We produced model-based estimates of excluding condition prevalence by site and year. As a sensitivity analysis, we repeated the analysis while including additional conditions in the outcome measure. We included 285,911 MRIs of the lumbar spine for low back pain. Generalized estimating equations regression found that outpatient hospitals had a higher proportion of MRIs with at least one excluding condition documented compared with outpatient clinics (P < .05), but increases in excluding condition prevalence were similar across all sites during 2009 to 2014. Our results were not sensitive to the inclusion of additional conditions. Documentation of excluding conditions and other clinically reasonable exclusions for OP-8 increased over time for outpatient hospitals and clinics. Increases in documentation of comorbidities may not translate to actual improvement in imaging appropriateness for low back pain. When accounting for all relevant conditions, the proportion of patients with low back pain considered uncomplicated and being measured by OP-8 would be small, reflecting a small proportion of patients with low back pain. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Footwear used by older people and a history of hyperkeratotic lesions on the foot

PubMed Central

Palomo-López, Patricia; Becerro-de-Bengoa-Vallejo, Ricardo; Losa-Iglesias, Marta Elena; Rodríguez-Sanz, David; Calvo-Lobo, César; López-López, Daniel

2017-01-01

Abstract Inadequate footwear, painful and hyperkeratotic lesions (HL) are an extremely common problems amongst older people. Such problems increase the risk of falls, hamper mobility, reduction of quality of life, dignity, and ability to remain independent. The etiology of painful and feet conditions is poorly understood. To discover footwear preferences of older people, pain tolerance may favor presence of HL for the use of inadequate footwear in old age. A sample of 100 participants with a mean age of 74.90 ± 7.01 years attended an outpatient clinic where self-reported demographic data, frequency with which they checked their feet were recorded and measurements were taken of foot sensitivity. Additionally, all participants’ shoes were allocated into optimal, adequate, and dangerous categories based on design, structural and safety features, and materials. Only 12% of the sample population checked their feet every day, 37% revealed symptoms of neuropathy, 14% used optimal shoes, and 61% presented HL. In a bivariate analysis, no significant differences were observed. HL are associated with inadequate footwear, loss of sensitivity, and low frequency of foot health checks. PMID:28403112

Sex differences in brain response to anticipated and experienced visceral pain in healthy subjects.

PubMed

Kano, Michiko; Farmer, Adam D; Aziz, Qasim; Giampietro, Vincent P; Brammer, Michael J; Williams, Steven C R; Fukudo, Shin; Coen, Steven J

2013-04-15

Women demonstrate higher pain sensitivity and prevalence of chronic visceral pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of visceral pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and pain induced by esophageal distension at pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending painful stimulation. During pain, women significantly activate brain areas associated with the affective and motivation components of pain. These responses may underlie the sex differences that exist in pain conditions, whereby women may attribute more emotional importance to painful stimuli compared with men.

Increased Evoked Potentials and Behavioral Indices in Response to Pain Among Individuals with Intellectual Disability.

PubMed

Benromano, Tali; Pick, Chaim G; Granovsky, Yelena; Defrin, Ruth

2017-09-01

Previous studies on the sensitivity and reactivity to pain of individuals with intellectual disability (ID) are inconsistent. The inconsistency may result from the reliance on self-reports and facial expressions of pain that are subject to internal and external biases. The aim was therefore to evaluate the reactivity to pain of individuals with ID by recording pain-evoked potentials (EPs), here for the first time, and testing their association with behavioral pain indices. Forty-one healthy adults, 16 with mild-moderate ID and 25 controls. Subjects received series of phasic heat stimuli and rated their pain on self-report scales. Changes in facial expressions and in pain EPs were recorded and analyzed offline. Pain self-reports, facial expressions, and the N2P2 amplitudes of the EPs exhibited stimulus-response relationship with stimulation intensity in both groups. The facial expressions and N2P2 amplitudes of individuals with ID were increased and N2P2 latency prolonged compared with controls. N2P2 amplitudes correlated with self-reports only in controls. Individuals with ID are hypersensitive/reactive to pain, a finding bearing clinical implications. Although pain EPs may reflect a somewhat different aspect of pain than the behavioral indices do, there is evidence to support their use to record pain in noncommunicative individuals, pending further validation. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The role of pain catastrophizing in experimental pain perception.

PubMed

Kristiansen, Frederik L; Olesen, Anne E; Brock, Christina; Gazerani, Parisa; Petrini, Laura; Mogil, Jeffrey S; Drewes, Asbjørn M

2014-03-01

Pain is a subjective experience influenced by multiple factors, and tremendous variety within individuals is present. To evaluate emotional state of pain, catastrophizing score can be used. This study investigated pain catastrophizing ratings in association with experimental pain perception. Experimental pain was induced using thermal heat and cold stimulation of skin, mechanical stimulation of muscle and bone, and thermal, mechanical, and electrical stimulation of the gastrointestinal tract in healthy participants (N = 41). Prior to experimental sessions, a pain catastrophizing questionnaire was filled out by each participant. Based on the median catastophizing score, participants were divided into two groups: noncatastrophizers and low-catastrophizers. No significant difference was found between low-catastrophizers and noncatastrophizers in thermal heat stimulation of skin, mechanical stimulation of muscle and bone, and rectal electrical stimulation (All P > 0.05). Low-catastrophizers were more sensitive to visceral thermal stimulation (4.7%, P = 0.02) and visceral mechanical stimulation (29.7%, P = 0.03). For participants that completed the 120 seconds ice water stimulation, noncatastrophizers reported 13.8% less pain than low-catastrophizers (P = 0.02). A positive correlation between PCS score and pain perception on cold pressor test was found (r = 0.4, P = 0.02). By extrapolating data, further analysis of the total group was performed and no differences (both P > 0.05) were observed. Even small increments in pain catastrophizing score can influence pain perception to deep and tonic stimulations. Catatrophizing may partly explain the variability found in experimental pain studies. © 2013 World Institute of Pain.

Cancer Pain: A Critical Review of Mechanism-based Classification and Physical Therapy Management in Palliative Care

PubMed Central

Kumar, Senthil P

2011-01-01

Mechanism-based classification and physical therapy management of pain is essential to effectively manage painful symptoms in patients attending palliative care. The objective of this review is to provide a detailed review of mechanism-based classification and physical therapy management of patients with cancer pain. Cancer pain can be classified based upon pain symptoms, pain mechanisms and pain syndromes. Classification based upon mechanisms not only addresses the underlying pathophysiology but also provides us with an understanding behind patient's symptoms and treatment responses. Existing evidence suggests that the five mechanisms – central sensitization, peripheral sensitization, sympathetically maintained pain, nociceptive and cognitive-affective – operate in patients with cancer pain. Summary of studies showing evidence for physical therapy treatment methods for cancer pain follows with suggested therapeutic implications. Effective palliative physical therapy care using a mechanism-based classification model should be tailored to suit each patient's findings, using a biopsychosocial model of pain. PMID:21976851

The roles of special proresolving mediators in pain relief.

PubMed

Zhang, Lan-Yu; Jia, Ming-Rui; Sun, Tao

2018-02-08

The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders. Due to the potent proresolving and anti-inflammatory effects, SPMs are also used for pain relief. This review focuses on the mechanisms by which SPMs act on their respective G-protein-coupled receptors in immune cells and nerve cells to normalize pain via regulating inflammatory mediators, transient receptor potential ion channels, and central sensitization. SPMs may offer novel therapeutic approaches for preventing and treating pain conditions associated with inflammation.

Do fibromyalgia patients benefit from cognitive restructuring and acceptance? An experimental study.

PubMed

Kohl, Annika; Rief, Winfried; Glombiewski, Julia Anna

2014-12-01

The aim of this study was to clarify mechanisms of psychological fibromyalgia treatment by experimentally examining the effectiveness of its core elements. We assessed the effects of cognitive restructuring and acceptance on experimentally-induced heat and cold pain tolerance and pain intensity in fibromyalgia patients. Cold and heat pain were induced in a sample of 60 fibromyalgia patients using a thermode. We conducted ANCOVAs to examine group differences in posttest scores, co-varying for pretest scores. The between-groups factor was the type of instruction provided (acceptance, cognitive restructuring, and a control condition). In addition, we controlled for pain sensitivity, age, and depression. We found that acceptance and cognitive restructuring were superior to the control condition in increasing heat pain tolerance, but did not differ from one another. With respect to cold pain tolerance, cognitive restructuring was associated with increases in cold pain tolerance compared to the control condition, while acceptance did not differ either from the control condition or from cognitive restructuring. Further experimental research on chronic pain treatment mechanisms is needed, particularly research on individually tailoring treatment strategies according to patients characteristics. Results show that both, cognitive restructuring and acceptance instructions, enhance pain tolerance in fibromyalgia patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Adherence Monitoring with Chronic Opioid Therapy for Persistent Pain: A Biopsychosocial-spiritual Approach to Mitigate Risk

PubMed Central

Matteliano, Deborah; St. Marie, Barbara J.; Oliver, June

2013-01-01

Opioids represent a mainstay in the pharmacological management of persistent pain. While these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a past history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing (ASPMN) Position Statement on Pain Management in Patients with Substance Use Disorders (2012) focuses on the intersection of persistent pain, SUD, and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to now include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. PMID:24602442

A preliminary study on how hypohydration affects pain perception.

PubMed

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

2016-05-01

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

Acute psychosocial stress reduces pain modulation capabilities in healthy men.

PubMed

Geva, Nirit; Pruessner, Jens; Defrin, Ruth

2014-11-01

Anecdotes on the ability of individuals to continue to function under stressful conditions despite injuries causing excruciating pain suggest that acute stress may induce analgesia. However, studies exploring the effect of acute experimental stress on pain perception show inconsistent results, possibly due to methodological differences. Our aim was to systematically study the effect of acute stress on pain perception using static and dynamic, state-of-the-art pain measurements. Participants were 29 healthy men who underwent the measurement of heat-pain threshold, heat-pain intolerance, temporal summation of pain, and conditioned pain modulation (CPM). Testing was conducted before and during exposure to the Montreal Imaging Stress Task (MIST), inducing acute psychosocial stress. Stress levels were evaluated using perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol. The MIST induced a significant stress reaction. Although pain threshold and pain intolerance were unaffected by stress, an increase in temporal summation of pain and a decrease in CPM were observed. These changes were significantly more robust among individuals with stronger reaction to stress ("high responders"), with a significant correlation between the perception of stress and the performance in the pain measurements. We conclude that acute psychosocial stress seems not to affect the sensitivity to pain, however, it significantly reduces the ability to modulate pain in a dose-response manner. Considering the diverse effects of stress in this and other studies, it appears that the type of stress and the magnitude of its appraisal determine its interactions with the pain system. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Evaluating an Innovative eLearning Pain Education Interprofessional Resource: A Pre-Post Study.

PubMed

Watt-Watson, Judy; McGillion, Michael; Lax, Leila; Oskarsson, Jon; Hunter, Judith; MacLennan, Cameron; Knickle, Kerry; Victor, J Charles

2018-06-20

The challenges of moving the pain education agenda forward are significant worldwide, and resources, including online, are needed to help educators in curriculum development. Online resources are available but with insufficient evaluation in the context of prelicensure pain education. Therefore, this pre-post study examined the impact of an innovative eLearning model: the Pain Education Interprofessional Resource (PEIR) on usability, pain knowledge, beliefs, and understanding of pain assessment skills including empathy. Participants were students (N = 96) recruited from seven prelicensure health sciences programs at the University of Toronto. They worked through three multifaceted modules, developed by an interprofessional team, that followed a patient with acute to persistent postsurgical pain up to one year. Module objectives, content, and assessment were based on International Association for the Study of Pain Pain Curricula domains and related pain core competencies. Multimedia interactive components focused on pain mechanisms and key pain care issues. Outcome measures included previously validated tools; data were analyzed in SPSS. Online exercises provided concurrent individual feedback throughout all modules. The completion rate for modules and online assessments was 100%. Overall usability scores (SD) were strong 4.27/5 (0.56). On average, pain knowledge scores increased 20% (P < 0.001). The Pain Assessment Skills Tool was sensitive to differences in student and expert pain assessment evaluation ratings and was useful as a tool to deliver formative feedback while engaged in interactive eLearning about pain assessment. PEIR is an effective eLearning program with high student ratings for educational design and usability that significantly improved pain knowledge and understanding of collaborative care.

Pain and the pathogenesis of biceps tendinopathy

PubMed Central

Raney, Elise B; Thankam, Finosh G; Dilisio, Matthew F; Agrawal, Devendra K

2017-01-01

Biceps tendinopathy is a relatively common ailment that typically presents as pain, tenderness, and weakness in the tendon of the long head of the biceps brachii. Though it is often associated with degenerative processes of the rotator cuff and the joint, this is not always the case, thus, the etiology remains considerably unknown. There has been recent interest in elucidating the pathogenesis of tendinopathy, since it can be an agent of chronic pain, and is difficult to manage. The purpose of this article is to critically evaluate relevant published research that reflects the current understanding of pain and how it relates to biceps tendinopathy. A review of the literature was conducted to create an organized picture of how pain arises and manifests itself, and how the mechanism behind biceps tendinopathy possibly results in pain. Chronic pain is thought to arise from neurogenic inflammation, central pain sensitization, excitatory nerve augmentation, inhibitory nerve loss, and/or dysregulation of supraspinal structures; thus, the connections of these theories to the ones regarding the generation of biceps tendinopathy, particularly the neural theory, are discussed. Pain mediators such as tachykinins, CGRP, and alarmins, in addition to nervous system ion channels, are highlighted as possible avenues for research in tendinopathy pain. Recognition of the nociceptive mechanisms and molecular of biceps tendinopathy might aid in the development of novel treatment strategies for managing anterior shoulder pain due to a symptomatic biceps tendon. PMID:28670360

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

PubMed

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

2017-09-01

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

Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.

PubMed

Koda, K; Hyakkoku, K; Ogawa, K; Takasu, K; Imai, S; Sakurai, Y; Fujita, M; Ono, H; Yamamoto, M; Fukuda, I; Yamane, S; Morita, A; Asaki, T; Kanemasa, T; Sakaguchi, G; Morioka, Y

2016-07-01

To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis. Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation. Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats. TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-08-01

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

The Missing “P” in Psychiatric Training: Why is it Important to Teach Pain to Psychiatrists?

PubMed Central

Elman, Igor; Zubieta, Jon-Kar; Borsook, David

2011-01-01

Context Pain problems are exceedingly prevalent among psychiatric patients. Moreover, clinical impressions and neurobiological research suggest that physical and psychological aspects of pain are closely related entities. Nonetheless, remarkably few pain-related themes are presently included in psychiatric residency training. Objective Our objective is twofold: (1) to provide clinical and scientific rationale for psychiatric training enrichment with basic tenets of pain medicine and (2) to raise the awareness and sensitivity of clinicians, scientists and educators alike to the important yet unmet clinical and public health need. Results Three lines of translational research evidence, extracted from the comprehensive literature review, are presented in support of the objective. First, the neuroanatomical and functional overlap between pain and emotion/reward/motivation brain circuits suggests integration and mutual modulation of these systems. Second, psychiatric disorders are commonly associated with alterations in pain processing, whereas chronic pain may impair emotional and neurocognitive functioning. Third, pain may serve as a functional probe for unraveling pathophysiological mechanisms inherent in psychiatric morbidity given its stressful nature for the organism. Conclusions Pain training in psychiatry will not only contribute to deeper and more sophisticated insights into pain syndromes but also into psychiatric morbidity at large regardless of patients’ pain status. Furthermore, it will ease artificial boundaries separating psychiatric and medical formulations of brain disorders, thus fostering cross-fertilizing interactions between specialists in various disciplines entrusted with the care of pain patients. PMID:21199962

Influence of variation in the catechol-O-methyltransferase gene on the clinical outcome after lumbar spine surgery for one-level symptomatic disc disease: a report on 176 cases.

PubMed

Rut, Marcin; Machoy-Mokrzyńska, Anna; Ręcławowicz, Daniel; Słoniewski, Paweł; Kurzawski, Mateusz; Droździk, Marek; Safranow, Krzysztof; Morawska, Michalina; Białecka, Monika

2014-02-01

This study was aimed at the evaluation of the relationship between genetic polymorphisms of catechol-O-methyltransferase (COMT) (rs4680:A > G-Val158Met, rs6269:A > G, rs4633:C > T, rs4818:C > G) and pain sensitivity after lumbar discectomy. All patients had one-level symptomatic disc herniation from L3 to S1. The primary data recorded included visual analogue pain scales assessing back and leg pain, Oswestry Disability Questionnaire assessing quality of life and pain intensity, received/filled pre- and postoperatively. Each subject was genotyped for single-nucleotide polymorphism in the COMT gene. Clinical outcome was measured by difference between pre- and postoperative values and those results were analyzed with genetics findings. Pain intensity was associated with the COMT polymorphism. Carriers of rs6269 AA, rs4633 TT, rs4818 CC, and rs4680 AA genotypes were characterized by the lowest preoperative scores related to pain intensity and lower pain intensity at 1 year after the surgery. The rs4633 CC, rs4680 GG genotypes demonstrated significant clinical improvement in VASBACK score at 1 year after the surgery. Patients with COMT haplotype associated with low metabolic activity of enzyme (A_C_C_G) showed better clinical outcome measured by ODI score and VASBACK score 1 year after surgery. We did not observe any significant correlation between leg pain and single-nucleotide polymorphisms in the COMT gene. The results of our study indicate that polymorphism in the COMT gene may play an important role in the mechanism of pain perception, which may have a potential implication for clinical decision-making in the future.

A PROMIS Measure of Neuropathic Pain Quality

PubMed Central

Askew, Robert L.; Cook, Karon F.; Keefe, Francis J.; Nowinski, Cindy J; Cella, David; Revicki, Dennis A.; DeWitt, Esi M. Morgan; Michaud, Kaleb; Trence, Dace L.; Amtmann, Dagmar

2016-01-01

Objectives Neuropathic pain is a consequence of many chronic conditions. This study aimed to develop a unidimensional neuropathic pain scale whose scores represent levels of neuropathic pain and distinguish between individuals with neuropathic and non-neuropathic pain conditions. Methods A candidate item pool of 42 pain quality descriptors was administered to participants with osteoarthritis, rheumatoid arthritis, diabetic neuropathy, and cancer chemotherapy-induced peripheral neuropathy. A subset of pain quality descriptors (items) that best distinguished between participants with and those without neuropathic pain conditions were identified. Dimensionality of pain descriptors was evaluated in a development sample and cross-validated in a hold-out sample. Item responses were calibrated using an item response theory model, and scores were generated on a T-score metric. Neuropathic pain scale scores were evaluated in terms of reliability, validity, and the ability to distinguish between participants with and without conditions typically associated with neuropathic pain. Results Of the 42 initial items, 5 were identified for the Patient Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality scale (PROMIS-PQ-Neuro). The IRT-generated T-scores exhibited good discriminatory ability based on receiver operator characteristic analysis. Score thresholds were identified that optimize sensitivity and specificity. Construct, criterion, and discriminant validity, and reliability of scale scores were supported. Conclusions The 5-item PROMIS PQ-Neuro is a short and practical measure that can be used to identify patients more likely to have neuropathic pain and to distinguish levels of neuropathic pain. The data collected will support future research that targets other unidimensional pain quality domains (e.g., nociceptive pain). PMID:27565279

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

PubMed

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

2013-01-01

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

The neural bases of social pain: Evidence for shared representations with physical pain

PubMed Central

Eisenberger, Naomi I.

2012-01-01

Experiences of social rejection or loss have been described as some of the most ‘painful’ experiences that we, as humans, face and perhaps for good reason. Because of our prolonged period of immaturity, the social attachment system may have co-opted the pain system, borrowing the pain signal to prevent the detrimental consequences of social separation. This review summarizes a program of research that has explored the idea that experiences of physical and social pain rely on shared neural substrates. First, evidence showing that social pain activates pain-related neural regions is reviewed. Then, studies exploring some of the expected consequences of such a physical-social pain overlap are summarized. These studies demonstrate: 1) that individuals who are more sensitive to one kind of pain are also more sensitive to the other and 2) that factors that increase or decrease one kind of pain alter the other in a similar manner. Finally, what these shared neural substrates mean for our understanding of socially painful experience is discussed. PMID:22286852

Conditioned Pain Modulation and Situational Pain Catastrophizing as Preoperative Predictors of Pain following Chest Wall Surgery: A Prospective Observational Cohort Study

PubMed Central

Grosen, Kasper; Vase, Lene; Pilegaard, Hans K.; Pfeiffer-Jensen, Mogens; Drewes, Asbjørn M.

2014-01-01

Background Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency. Methods Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively. Results Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001). Conclusions Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have important implications for developing strategies to treat or prevent acute postoperative pain in selected patients. Pain may be predicted and the malfunctioning pain inhibition mechanism as tested with CPM may be treated with suitable drugs augmenting descending inhibition. PMID:24587268

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

Visceral pain hypersensitivity in functional gastrointestinal disorders.

PubMed

Farmer, A D; Aziz, Q

2009-01-01

Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

Bilateral widespread mechanical pain hypersensitivity as sign of central sensitization in patients with cluster headache.

PubMed

Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Cuadrado, María L; López-de-Silanes, Carlos; Pareja, Juan A

2011-03-01

To investigate bilateral widespread pressure pain hyperalgesia in deep tissues over symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with cluster headache (CH). Central sensitization is claimed to play a relevant role in CH. No study has previously searched for widespread pressure hyperalgesia in deep tissues over both symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with CH. Sixteen men (mean age: 43 ± 11 years) with CH in a remission phase and 16 matched controls were recruited. Pressure pain thresholds (PPTs) were bilaterally measured over the supra-orbital (V1), infra-orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves, C5-C6 zygapophyseal joint, mastoid process, and tibialis anterior muscle by an assessor blinded to the subjects' condition. The results showed that PPT levels were significantly decreased bilaterally in patients with CH as compared with healthy controls (all sites, P < .001). A greater degree of sensitization over the mastoid process (P < .001) and a lower degree of sensitization over the tibialis anterior muscle (P < .01) was found. Our findings revealed bilateral widespread pressure pain hypersensitivity in patients with CH confirming the presence of central sensitization mechanisms in this headache condition. © 2010 American Headache Society.

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

PubMed

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

2016-01-01

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

Risk Factors for Low Back Pain in Childhood and Adolescence: A Systematic Review.

PubMed

Calvo-Muñoz, Inmaculada; Kovacs, Francisco M; Roqué, Marta; Gago Fernández, Inés; Seco Calvo, Jesús

2018-05-01

To identify factors associated with low back pain (LBP) in children and adolescents. A systematic review was conducted (Prospero CRD42016038186). Observational studies analyzing LBP risk factors among participants aged between 9 and 16 were searched for in 13 electronic databases and 8 specialized journals until March 31, 2016, with no language restrictions. In addition, references in the identified studies were manually tracked. All identified studies that included ≥50 participants aged 9 to 16, were reviewed. Their methodological quality was assessed by 2 reviewers separately, using validated tools, which scored, from worst to best, 0 to 100 for cross-sectional and 0 to 12 for cohort studies. A sensitivity analysis only included studies that had adjusted for confounders, had ≥500 participants, and had a methodological score of ≥50%. A total of 5142 citations were screened and 61 studies, including 137,877 participants from 5 continents, were reviewed. Their mean (range) methodological scores were 74.56 (50 to 100) for cross-sectional studies and 7.36 (5 to 9) for cohort studies. The studies had assessed 35 demographic, clinical, biological, family, psychological, ergonomic, and lifestyle risk factors. The mean (range) prevalence of LBP ranged between 15.25% (3.20 to 57.00) for point prevalence and 38.98% (11.60 to 85.56) for lifetime prevalence. Results on the association between LBP and risk factors were inconsistent. In the sensitivity analysis, "older age" and "participation in competitive sports" showed a consistent association with LBP. Future studies should focus on muscle characteristics, the relationship between body and backpack weights, duration of carrying the backpack, characteristics of sport practice, and which are the factors associated with specifically chronic pain.