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Sample records for laboratory pain sensitivity

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2016-12-01

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

  4. Pain Sensitivity in Sleepy Pain-Free Normals

    PubMed Central

    Chhangani, Bantu Samridhi; Roehrs, Timothy A.; Harris, Erica J.; Hyde, Maren; Drake, Christopher; Hudgel, David W.; Roth, Thomas

    2009-01-01

    Study Objective: Past studies have shown that acute experimental reduction of time in bed in otherwise healthy, non-sleepy people leads to hyperalgesia. We hypothesized that otherwise healthy, sleepy people may also exhibit hyperalgesia relative to their non-sleepy counterparts. Design: Between-groups sleep laboratory study. Setting: Hospital-based sleep disorders center. Participants: Twenty-seven, healthy, normal participants (age 18–35 years) were recruited and categorized into sleepy and non-sleepy groups based on their average sleep latencies on a screening multiple sleep latency test (MSLT). Interventions: Both groups were then allowed 8 hours time in bed, following which they underwent pain sensitivity testing (10:30 and 14:30) and sleepiness assessments by the MSLT (10:00, 12:00, 14:00, and 16:00). Pain sensitivity assessments were made by measuring finger withdrawal latencies to a radiant heat source delivering 5 different heat intensities. Measurements and Results: This study showed that after only one night of 8 hours time in bed, the sleepy participants continued to be sleepy and exhibited a more rapid finger withdrawal response (i.e., increased pain sensitivity) to radiant heat than non-sleepy participants. Conclusion: This suggests that sleepy individuals experience hyperalgesia in response to a painful stimulus when compared with non-sleepy individuals. Citation: Chhangani BS; Roehrs TA; Harris EJ; Hyde M; Drake C; Hudgel DW; Roth T. Pain sensitivity in sleepy pain-free normals. SLEEP 2009;32(8):1011-1017. PMID:19725252

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

    PubMed

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

    2008-01-01

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

  6. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    PubMed Central

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  8. 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.

  9. Pain Sensitivity and Pain Catastrophizing are Associated with Persistent Pain and Disability after Lumbar Spine Surgery

    PubMed Central

    Coronado, Rogelio A.; George, Steven Z.; Devin, Clinton J.; Wegener, Stephen T.; Archer, Kristin R.

    2015-01-01

    Objective To examine whether pain sensitivity and pain catastrophizing are associated with persistent pain and disability after lumbar spine surgery. Design Prospective observational cohort study. Setting Academic medical center. Participants Patients (N = 68, mean ± SD age = 57.9 ± 13.1 years, N female = 40 (58.8%)) undergoing spine surgery for a degenerative condition from March 1, 2012 to April 30, 2013 were assessed 6 weeks, 3 months, and 6 months after surgery. Interventions Not applicable. Main Outcome Measure(s) The main outcome measures were persistent back pain intensity, pain interference, and disability. Patients with persistent back pain intensity, pain interference, or disability were identified as those patients reporting Brief Pain Inventory scores ≥ 4 and Oswestry Disability Index scores ≥ 21 at all postoperative time points. Results From 6 weeks to 6 months after surgery, approximately 12.9%, 24.2%, and 46.8% of patients reported persistent back pain intensity, pain interference, or disability, respectively. Increased pain sensitivity at 6 weeks was associated with having persistent back pain intensity (OR = 2.0, 95% CI = 1.0; 4.1) after surgery. Increased pain catastrophizing at 6 weeks was associated with having persistent back pain intensity (OR = 1.1, 95% CI = 1.0; 1.2), pain interference (OR = 1.1, 95% CI = 1.0; 1.2), and disability (OR = 1.3, 95% CI = 1.1; 1.4). An interaction effect was not found between pain sensitivity and pain catastrophizing on persistent outcomes (p > 0.05). Conclusion(s) Findings suggest the importance of early postoperative screening for pain sensitivity and pain catastrophizing in order to identify patients at-risk for poor postoperative pain intensity, interference, and/or disability outcomes. Future research should consider the benefit of targeted therapeutic strategies for patients with these postoperative prognostic factors. PMID:26101845

  10. Cockroach sensitization in laboratory workers.

    PubMed

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

    1987-10-01

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

  11. Pediatric Pain, Predictive Inference, and Sensitivity Analysis.

    ERIC Educational Resources Information Center

    Weiss, Robert

    1994-01-01

    Coping style and effects of counseling intervention on pain tolerance was studied for 61 elementary school students through immersion of hands in cold water. Bayesian predictive inference tools are able to distinguish between subject characteristics and manipulable treatments. Sensitivity analysis strengthens the certainty of conclusions about…

  12. 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.

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

    PubMed Central

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

    2016-01-01

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

  14. 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

  15. The effect of disgust on pain sensitivity.

    PubMed

    Oaten, Megan J; Stevenson, Richard J; Case, Trevor I

    2015-01-01

    Experiencing the emotion of disgust leads to delayed up-regulation of immune-related functions, increased core-body temperature and reduced appetite. These changes parallel those of the acute phase response, which occurs when a pathogen is detected by the immune system. Here we examined whether a further predicted aspect of the acute phase response is evident following disgust induction, namely increased pain sensitivity. Participants attended a two-session experiment. On one session they experienced an emotion induction (being randomly assigned to either disgust, negative or positive groups) and on the other they received a neutral control induction. Before and after each induction, and at 15 and 30min post-induction, participants engaged in a cold-pressor task, rating pain intensity at 10s intervals for 90s on each occasion. Relative to neutral control and pre-test, average pain intensity decreased then increased across time following the disgust induction, with the reverse pattern in the negative and positive emotion inductions. These findings are the first to suggest that disgust may lead to an increase in pain sensitivity over a time course paralleling changes observed for core-body temperature and immune-related function, although the mechanisms underpinning these effects remain to be identified. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Decreased pain sensitivity due to trimethylbenzene exposure ...

    EPA Pesticide Factsheets

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

  17. Multi-Ethnic Differences in Responses to Laboratory Pain Stimuli among Children

    PubMed Central

    Lu, Qian; Zeltzer, Lonnie; Tsao, Jennie

    2013-01-01

    Objective A growing body of literature suggests ethnic differences in experimental pain. However, these studies largely focus on adults and the comparison between Caucasians and African-Americans. The primary aim of this study is to determine ethnic differences in laboratory induced pain in a multi-ethnic child sample. Methods Participants were 214 healthy children (mean age = 12.7, SD= 3.0 yrs). Ninety-eight Caucasian, 58 Hispanic, 34 African-American, and 24 Asian children were exposed to four trials of pressure and radiant heat pain stimuli. Pain responses were assessed with self-report measures (i.e., pain intensity and unpleasantness) and behavioral observation (i.e., pain tolerance). Results Asians demonstrated more pain sensitivity than Caucasians, who evidenced more pain sensitivity than African-Americans and Hispanics. The results hold even after controlling for age, sex, SES, and experimenter’s ethnicity. Asians also showed higher anticipatory anxiety compared with other ethnic groups. Anticipatory anxiety accounted for some ethnic differences in pain between Asians, Hispanics, and African Americans. Conclusions By examining response to laboratory pain stimuli in children representing multiple ethnicities, an understudied sample, the study reveals unique findings compared to the existing literature. These findings have implications for clinicians who manage acute pain in children from diverse ethnic backgrounds. Future investigations should examine mechanisms that account for ethnic differences in pain during various developmental stages. PMID:23668844

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

    PubMed

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

    2016-09-01

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

  19. Napping Reverses Increased Pain Sensitivity Due to Sleep Restriction

    PubMed Central

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

    2015-01-01

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

  20. Ethnic Identity Predicts Experimental Pain Sensitivity In African Americans and Hispanics

    PubMed Central

    Rahim-Williams, F. Bridgett; Riley, Joseph L.; Herrera, Dyanne; Campbell, Claudia; Hastie, Barbara A.; Fillingim, Roger B.

    2007-01-01

    The aim of this study was to examine experimental pain sensitivity in three ethnic groups, African Americans, Hispanic Americans and non-Hispanic whites, and to determine whether ethnic identity is differentially associated with pain sensitivity across ethnic groups. Participants included sixty-three African American, sixty-one Hispanic and eighty-two non-Hispanic white participants who were assessed using three experimental pain measures: thermal, cold-pressor and ischemic. Participants’ ethnic identity was assessed using the Multi-group Ethnic Identity Measure (MEIM). Ethnic group differences in pain responses were observed, with African American and Hispanic subjects showing lower cold and heat pain tolerances than non-Hispanic whites. In addition, pain range (i.e. tolerance – threshold) was computed for heat, cold and ischemic pain, and the two minority groups again had lower values compared to non-Hispanic whites. Ethnic identity was associated with pain range only for African American and Hispanic groups. Statistically controlling for ethnic identity rendered some of the group differences in pain range non-significant. These findings indicate that ethnic identity is associated with pain sensitivity in ethnic minority groups, and may partially mediate group differences in pain perception. The results of the present investigation provide evidence of ethnic group differences in responses to experimental pain across multiple noxious stimuli, with both minority groups exhibiting greater sensitivity to laboratory evoked pain compared to non-Hispanic whites. PMID:17296267

  1. Latent sensitization: a model for stress-sensitive chronic pain.

    PubMed

    Marvizon, Juan Carlos; Walwyn, Wendy; Minasyan, Ani; Chen, Wenling; Taylor, Bradley K

    2015-04-01

    Latent sensitization is a rodent model of chronic pain that reproduces both its episodic nature and its sensitivity to stress. It is triggered by a wide variety of injuries ranging from injection of inflammatory agents to nerve damage. It follows a characteristic time course in which a hyperalgesic phase is followed by a phase of remission. The hyperalgesic phase lasts between a few days to several months, depending on the triggering injury. Injection of μ-opioid receptor inverse agonists (e.g., naloxone or naltrexone) during the remission phase induces reinstatement of hyperalgesia. This indicates that the remission phase does not represent a return to the normal state, but rather an altered state in which hyperalgesia is masked by constitutive activity of opioid receptors. Importantly, stress also triggers reinstatement. Here we describe in detail procedures for inducing and following latent sensitization in its different phases in rats and mice. Copyright © 2015 John Wiley & Sons, Inc.

  2. Latent Sensitization: a model for stress-sensitive chronic pain

    PubMed Central

    Marvizon, Juan Carlos; Walwyn, Wendy; Minasyan, Ani; Chen, Wenling; Taylor, Bradley K.

    2015-01-01

    Latent sensitization is a rodent model of chronic pain that reproduces both its episodic nature and its sensitivity to stress. It is triggered by a wide variety of injuries ranging from injection of inflammatory agents to nerve damage. It follows a characteristic time course in which a hyperalgesic phase is followed by a phase of remission. The hyperalgesic phase lasts between a few days to several months, depending of the triggering injury. Injection of μ-opioid receptor inverse agonists (i.e., naloxone, naltrexone) during the remission phase induces reinstatement of hyperalgesia. This indicates that the remission phase does not represent a return to the normal state, but rather an altered state in which hyperalgesia is masked by constitutive activity of opioid receptors. Importantly, stress also triggers reinstatement. Here we describe in detail the procedures to induce and follow latent sensitization in its different phases in rats and mice. PMID:25829356

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

    PubMed Central

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

    2015-01-01

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

  4. Pain sensitivity can be assessed by self-rating: Development and validation of the Pain Sensitivity Questionnaire.

    PubMed

    Ruscheweyh, Ruth; Marziniak, Martin; Stumpenhorst, Frederike; Reinholz, Julia; Knecht, Stefan

    2009-11-01

    Experimental determination of pain sensitivity has received increasing attention because of emerging clinical applications (including prediction of postoperative pain and treatment response) and scientific implications (e.g. it has been proposed that above-average pain sensitivity is a risk factor for the development of chronic pain disorders). However, the use of experimental pain sensitivity assessment on a broad scale is hampered by its requirements on time, equipment and human resources and the fact that it is painful for the tested subject. Alternatives to experimental pain testing are currently lacking. Here we developed a self-rating instrument for the assessment of pain sensitivity, the Pain Sensitivity Questionnaire (PSQ) that is based on pain intensity ratings of daily life situations and takes 5-10min to complete. Adequate reliability of the PSQ was confirmed in 354 subjects. In a validation study comprising 47 healthy subjects, the results of comprehensive experimental pain testing, including different modalities (heat, cold, pressure, and pinprick) and different measures (pain thresholds, pain intensity ratings), were compared to the results of the PSQ. PSQ scores were significantly correlated to experimental pain intensity ratings (r = 0.56, p < 0.001) but not to pain thresholds (r = 0.03). Prediction of experimental pain intensity ratings by the PSQ was better than by pain-associated psychological factors (pain catastrophizing, depression, anxiety). This shows that the PSQ may be a simple alternative to experimental pain intensity rating procedures in healthy subjects and makes the PSQ a highly promising tool for clinical and experimental pain research.

  5. Laboratory personnel gender and cold pressor apparatus affect subjective pain reports

    PubMed Central

    Vigil, Jacob M; Rowell, Lauren N; Alcock, Joe; Maestes, Randy

    2014-01-01

    BACKGROUND: There is no standardized method for cold pressor pain tasks across experiments. Temperature, apparatus and aspects of experimenters vary widely among studies. It is well known that experimental pain tolerance is influenced by setting as well as the sex of the experimenter. It is not known whether other contextual factors influence experimental pain reporting. OBJECTIVES: The present two-part experiment examines whether minimizing and standardizing interactions with laboratory personnel (eg, limiting interaction with participants to consenting and questions and not during the actual pain task) eliminates the influence of examiner characteristics on subjective pain reports and whether using different cold pain apparatus (cooler versus machine) influences reports. METHODS: The present experiment manipulated the gender of the experimenter (male, female and transgender) and the type of cold pressor task (CPT) apparatus (ice cooler versus refrigerated bath circulator). Participants conducted the CPT at one of two pain levels (5°C or 16°C) without an experimenter present. RESULTS: Men and women showed lower pain sensitivity when they were processed by biological male personnel than by biological female personnel before the CPT. Women who interacted with a transgendered researcher likewise reported higher pain sensitivity than women processed by biological male or female researchers. The type of CPT apparatus, despite operating at equivalent temperatures, also influenced subjective pain reports. DISCUSSION: The findings show that even minimal interactions with laboratory personnel who differ in gender, and differences in laboratory materials impact the reliable measurement of pain. CONCLUSION: More standardized protocols for measuring pain across varying research and clinical settings should be developed. PMID:24367796

  6. Heightened cold pain and pressure pain sensitivity in young female adults with moderate-to-severe menstrual pain.

    PubMed

    Slater, Helen; Paananen, Markus; Smith, Anne J; OʼSullivan, Peter; Briggs, Andrew M; Hickey, Martha; Mountain, Jenny; Karppinen, Jaro; Beales, Darren

    2015-12-01

    This study investigated the association between menstrual pain severity and psychophysical measures of cold and pressure pain sensitivity. A cross-sectional design was used with young women (n = 432) from the Western Australian Pregnancy Cohort (Raine) Study. Menstrual pain severity and oral contraception use was obtained from questionnaires at 20 and 22-year follow-ups. A visual analog scale (VAS; range from 0 [none] to 10 [unbearable]) was used to measure menstrual pain severity at both 20 and 22 years over the 3-year period, with 3 groups created: (1) no pain or mild pain (VAS 0-3), (2) at least moderate pain at a minimum of 1 of the 2 time points (hereafter named "mixed)", and (3) severe pain (VAS 8-10). Cold pain sensitivity (dorsal wrist) and pressure pain sensitivity (lumbar spine, upper trapezius, dorsal wrist, and tibialis anterior) were assessed using standardised quantitative sensory testing protocols. Confounding variables included number of musculoskeletal pain sites, oral contraceptive use, smoking, physical activity, body mass index, psychological distress, and sleep. Severe menstrual pain and mixed menstrual pain were positively associated with heightened cold pain sensitivity (distant from menstrual pain referral site) and pressure pain sensitivity (local to menstrual pain referral site). These associations remained significant after adjusting for potential confounding variables including multisite musculoskeletal pain. Our findings suggest peripheral and central neurophysiological mechanisms contributing to heightened pain sensitivity in young women with moderate and severe menstrual pain. These data highlight the need for innovative management approaches to attenuate the negative impact of severe menstrual pain in young women.

  7. 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.

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

    PubMed

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

    2017-03-01

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

  9. 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

  10. Characteristics of sensitization associated with chronic pain conditions

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2006-03-01

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

  12. 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

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

    PubMed

    Woolf, Clifford J

    2011-03-01

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

  14. 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.

  15. Salivary cortisol and cold pain sensitivity in female twins.

    PubMed

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

    2014-04-01

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

  16. Differential methylation of the TRPA1 promoter in pain sensitivity

    PubMed Central

    Bell, J.T.; Loomis, A.K.; Butcher, L.M.; Gao, F.; Zhang, B.; Hyde, C.L.; Sun, J.; Wu, H.; Ward, K.; Harris, J.; Scollen, S.; Davies, M.N.; Schalkwyk, L.C.; Mill, J.; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Deloukas, Panos; Dermitzakis, Emmanoil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Grundberg, Elin; Hassanali, Neelam; Hedman, Asa K.; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; McCarthy, Mark I.; Meduri, Eshwar; di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O’Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Soranzo, Nicole; Spector, Tim D.; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun-Po; Zondervan, Krina T.; Williams, F.M.K.; Li, N.; Deloukas, P.; Beck, S.; McMahon, S.B.; Wang, J.; John, S.L.; Spector, T.D.

    2014-01-01

    Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole-blood DNA methylation was characterized at 5.2 million loci by MeDIP sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain sensitivity (pain DMRs). Nine meta-analysis pain DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2 × 10−13). Several pain DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in the brain and altered expression in the skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits. PMID:24496475

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

    PubMed Central

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

    2015-01-01

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

  18. The role of sensitization in musculoskeletal shoulder pain

    PubMed Central

    Borstad, John; Woeste, Christopher

    2015-01-01

    Introduction: Peripheral and central sensitization are neurophysiological processes that can prolong painful conditions. Painful shoulder conditions are often persistent, perhaps due to the presence of sensitization. Method: This manuscript summarizes six studies that have evaluated those with musculoskeletal shoulder pain for the presence of sensitization. Results: All six manuscripts report evidence of peripheral sensitization, while central sensitization was described in five of the studies. The chronicity of symptoms in subjects who were included in the studies is probably influencing this finding. The primary somatosensory test used to assess sensitization in these studies was Pressure Pain Threshold, a test for lowered nociceptive thresholds. Discussion: It appears that peripheral sensitization manifests consistently in those with musculoskeletal shoulder pathology, probably due to the inflammatory processes related to tissue injury. Central sensitization, while not universally present, was reported in a majority of the manuscripts. Because central sensitization is thought to be a key step on the pathway to chronic pain, evidence for its presence in those with shoulder pain is significant. Clinicians should expect the presence of sensitization with shoulder pathology and make appropriate choices about interventions so as not to exacerbate pain. PMID:26443971

  19. Anxiety sensitivity and pain: generalisability across noxious stimuli.

    PubMed

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

    2008-01-01

    Anxiety sensitivity, a fear of anxiety-related symptoms, has been associated with a heightened experience of pain, especially within women. The majority of experimental studies investigating this association have relied heavily on the cold pressor technique as a means of pain induction, limiting the generalisability of results. The aim of the current study was to extend previous research by using two types of pain stimuli (cold and heat) to determine whether the link between anxiety sensitivity and pain generalises beyond cold pressor pain. The pain experience of 125 participants in response to these stimuli was assessed using threshold and tolerance readings, as well as subjective pain ratings. Results indicated a positive association between anxiety sensitivity and subjective pain, with this association observed primarily in females. Although analysis also indicated a basic generalisability of results across pain stimuli, anxiety sensitivity effects appeared to be especially pronounced during heat stimulation. These findings suggest that those high in anxiety sensitivity may respond more negatively to specific types of pain. Possible implications along with suggestions for future research are discussed.

  20. Cognitive-emotional sensitization contributes to wind-up-like pain in phantom limb pain patients.

    PubMed

    Vase, Lene; Nikolajsen, Lone; Christensen, Bente; Egsgaard, Line Lindhart; Arendt-Nielsen, Lars; Svensson, Peter; Staehelin Jensen, Troels

    2011-01-01

    Peripheral mechanisms are known to play a role in phantom pain following limb amputation, and more recently it has been suggested that central mechanisms may also be of importance. Some patients seem to have a psychological sensitivity that predisposes them to react with pain catastrophizing after amputation of a limb, and this coping style may contribute to increased facilitation, impaired modulation of nociceptive signals, or both. To investigate how pain catastrophizing, independently of anxiety and depression, may contribute to phantom limb pain and to alterations in pain processing twenty-four upper-limb amputees with various levels of phantom limb pain were included in the study. Patients' level of pain catastrophizing, anxiety and depression was assessed and they went through quantitative sensory testing (QST) of thresholds (mechanical and thermal) and wind-up-like pain (brush and pinprick). Catastrophizing accounted for 35% of the variance in phantom limb pain (p=0.001) independently of anxiety and depression. Catastrophizing was also positively associated with wind-up-like pain in non-medicated patients (p=0.015), but not to pain thresholds. These findings suggest that cognitive-emotional sensitization contributes to the altered nociceptive processing seen in phantom limb pain patients. The possible interactions between pain catastrophizing, wind-up-like pain, and peripheral input in generating and maintaining phantom limb pain are discussed.

  1. Imaging and laboratory testing in acute abdominal pain.

    PubMed

    Panebianco, Nova L; Jahnes, Katherine; Mills, Angela M

    2011-05-01

    When discussing which laboratory tests or imaging to order in the setting of acute abdominal pain, it is practical to organize information by disease process (eg, acute appendicitis, cholecystitis). Because studies on the accuracy of diagnostic tests are of necessity related to the presence or absence of specific diagnoses, and because clinicians frequently look to tests to help them rule in or rule out specific conditions, this article is organized by region of pain and common abdominal diagnoses. It focuses on the contributions that laboratory testing and imaging make in the emergency management of abdominal complaints. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Prediction of postoperative pain intensity after lumbar spinal surgery using pain sensitivity and preoperative back pain severity.

    PubMed

    Kim, Ho-Joong; Park, Joon-Hee; Kim, Jang-Woo; Kang, Kyoung-Tak; Chang, Bong-Soon; Lee, Choon-Ki; Yeom, Jin S

    2014-12-01

    To investigate the role of preoperative pain sensitivity and preoperative symptom severity for prediction of postoperative pain intensity after lumbar spine surgery. This study consisted of two groups who underwent decompression surgery alone (62 patients) or decompression with fusion surgery (37 patients) for lumbar spinal stenosis (LSS). Pain Sensitivity Questionnaire (PSQ) and visual analog pain scale (VAS) for back pain and leg pain were collected preoperatively with detailed medical history. The assessment was performed immediately after surgery when the patients had completely recovered and regained their complete consciousness from general anesthesia (H0) and subsequently 4, 8, 18, 30, 48, and 72 hours (H4, H8, H18, H30, H48, and H72) thereafter as they recovered. Both groups showed a decrease in back pain and leg pain with the time postoperatively. In fusion group, preoperative VAS for back pain was significantly correlated with postoperative VAS for back pain at H0, H4, H8, and H18, and PSQ minor/total PSQ also showed a significant correlation with postoperative back pain at H48 and H72. In contrast, only total PSQ and PSQ minors were significantly correlated with postoperative back pain at H18 and H30 in decompression group. Hierarchical regression analysis finally showed that each preoperative back pain and PSQ minor was predictive of immediate postoperative back pain (from H0 to H18) in fusion group and delayed postoperative back pain (H18, H30) in decompression group. The study highlights that each preoperative back pain and individual pain sensitivity could predict the different aspects of postoperative pain after lumbar surgery. Wiley Periodicals, Inc.

  3. 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

  4. Mucosal versus muscle pain sensitivity in provoked vestibulodynia

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2016-01-01

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

  6. Affect balance style, experimental pain sensitivity, and pain-related responses

    PubMed Central

    Sibille, Kimberly T.; Kindler, Lindsay L.; Glover, Toni L.; Staud, Roland; Riley, Joseph L.; Fillingim, Roger B.

    2011-01-01

    Objectives Affect is neurobiologically based, influences emotions, contributes to temperamental characteristics, and can be evaluated from both a state and trait perspective. Associations between state-related positive affect (PA), negative affect (NA), and chronic pain have been investigated. However, little is known about the relationship between trait affect patterns and pain-related experiences. Affect balance style (ABS) provides a framework to assess the combined contribution of trait PA and NA. Psychological factors and experimental pain sensitivity are indicated as predictors of chronic pain onset. The current study investigated the relationship between ABS, pain sensitivity, and pain-related measures in healthy adults. Methods Subjects (n=372) completed quantitative sensory testing, pain-related questionnaires, and the Positive and Negative Affect Scale (PANAS). ABS groups were categorized as Healthy (high PA, low NA), Low (low PA, low NA), Depressive (low PA, high NA), and Reactive (high PA, high NA). Z-scores were computed for three experimental pain measures: ischemic, pressure, and heat. Results ABS groups significantly differed on ischemic pain sensitivity and pain-related measures. Specifically, the Healthy group demonstrated lower ischemic pain sensitivity compared to the Reactive group (p=0.02); the Depressive and Reactive groups endorsed higher somatic symptoms compared to the Healthy group (p<0.02); the Low and Depressive groups reported more physical stimuli sensitivity than the Healthy group (p<0.02); and the Reactive group indicated more passive coping strategies then the Low and Healthy groups (p=0.001). Discussion Findings from the study suggest that among healthy adults, trait affect patterns are associated with ischemic experimental pain sensitivity and other pain-related measures. PMID:22367502

  7. Affect balance style, experimental pain sensitivity, and pain-related responses.

    PubMed

    Sibille, Kimberly T; Kindler, Lindsay L; Glover, Toni L; Staud, Roland; Riley, Joseph L; Fillingim, Roger B

    2012-06-01

    Affect is neurobiologically based, influences emotions, contributes to temperamental characteristics, and can be evaluated from both state and trait perspectives. Associations between state-related positive affect (PA), negative affect (NA), and chronic pain have been investigated. However, little is known about the relationship between trait affect patterns and pain-related experiences. Affect balance style (ABS) provides a framework to assess the combined contribution of trait PA and NA. Psychological factors and experimental pain sensitivity are indicated as predictors of chronic pain onset. The current study investigated the relationship between ABS, pain sensitivity, and pain-related measures in healthy adults. Participants (n=372) completed quantitative sensory testing, pain-related questionnaires, and the Positive and Negative Affect Scale. ABS groups were categorized as Healthy (high PA, low NA), Low (low PA, low NA), Depressive (low PA, high NA), and Reactive (high PA, high NA). Z-scores were computed for 3 experimental pain measures: ischemic, pressure, and heat. ABS groups significantly differed on ischemic pain sensitivity and pain-related measures. Specifically, the Healthy group demonstrated lower ischemic pain sensitivity compared with the Reactive group (P=0.02); the Depressive and Reactive groups endorsed higher somatic symptoms compared with the Healthy group (P<0.02); the Low and Depressive groups reported more physical stimuli sensitivity than the Healthy group (P<0.02); and the Reactive group indicated more passive coping strategies then the Low and Healthy groups (P=0.001). Findings from the study suggest that among healthy adults, trait affect patterns are associated with ischemic experimental pain sensitivity and other pain-related measures.

  8. Relationship between resting blood pressure and laboratory-induced pain among healthy children.

    PubMed

    Haas, Kelly; Lu, Qian; Evans, Subhadra; Tsao, Jennie C I; Zeltzer, Lonnie K

    2011-12-01

    Adult studies have demonstrated that increased resting blood pressure (BP) levels correlate with decreased pain sensitivity. However, few studies have examined the relationship between BP and experimental pain sensitivity among children. This study investigated the association between resting BP levels and experimental pain tolerance, intensity, and unpleasantness in healthy children. We also explored whether these BP-pain relationships were age and gender dependent. Participants underwent separate 4-trial blocks of cutaneous pressure and thermal pain stimuli, and 1 trial of a cold pain stimulus in counterbalanced order. A total of 235 healthy children (49.6% female; mean age 12.7 [2.9] years; age range 8-18 years) participated. The study revealed specific gender-based BP-pain relationships. Girls with higher resting systolic BP levels were found to have lower thermal intensity ratings than girls with lower resting systolic BP levels; this relationship was stronger among adolescent girls than among younger girls. Among young girls (8-11 years), those with higher resting diastolic BP (DBP) levels were found to have lower cold intensity and unpleasantness as well as lower thermal intensity ratings than did young girls with lower resting DBP levels; these DBP-pain response relationships were not seen among adolescent girls. Age, rather than resting BP, was predictive of laboratory pain ratings in boys. The findings suggest that the relationship between BP and experimental pain is age and gender dependent. These aspects of cardiovascular relationships to pain in males and females need further attention to understand their clinical importance. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  9. 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

  10. Cortical thickness correlates of pain and temperature sensitivity.

    PubMed

    Erpelding, Nathalie; Moayedi, Massieh; Davis, Karen D

    2012-08-01

    It is well established that there is individual variability in pain and temperature sensitivity. Functional brain imaging studies have found that interindividual heat pain variability correlates with brain activity in sensory and pain modulation areas. Thus, it is possible that these individual differences are associated with variability in gray matter thickness of cortical regions involved in thermoreception and pain. To test this, we investigated the relationship between thermal thresholds and cortical thickness in 80 healthy subjects. Subjects underwent a psychophysical session to determine their cool detection (CD), warm detection (WD), cold pain (CP), and heat pain (HP) threshold. A high-resolution structural magnetic resonance imaging scan was acquired for each subject. We correlated each threshold measure to cortical thickness of regions associated with thermoreception and pain. The mean (± SD) thresholds were 30.7 °C (± 0.8) for CD, 33.8 °C (± 0.7) for WD, 11.7 °C (± 9.7) for CP, and 45.3 °C (± 2.8) for HP. The brain gray matter analysis revealed a strong correlation between greater thermal and pain sensitivity and cortical thickening of the primary somatosensory cortex. Additionally, greater sensitivity to cool stimuli correlated with cortical thickening in the paracentral lobule, and greater WD correlated with cortical thinning in the anterior midcingulate cortex. We also found that greater HP sensitivity correlated with thickening in the posterior midcingulate cortex and the orbitofrontal cortex. These cortical gray matter correlates of thermal and pain sensitivity provide a neural basis for individual differences in thermal sensitivity. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  11. 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

  12. 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.

  13. [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.

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

    Chronic pelvic pain is a frustrating symptom for patients with endometriosis and is frequently refractory to hormonal and surgical management. While these therapies target ectopic endometrial lesions, they do not directly address pain due to central sensitization of the nervous system and myofascial dysfunction, which can continue to generate pain from myofascial trigger points even after traditional treatments are optimized. This article provides a background for understanding how endometriosis facilitates remodeling of neural networks, contributing to sensitization and generation of myofascial trigger points. A framework for evaluating such sensitization and myofascial trigger points in a clinical setting is presented. Treatments that specifically address myofascial pain secondary to spontaneously painful myofascial trigger points and their putative mechanisms of action are also reviewed, including physical therapy, dry needling, anesthetic injections, and botulinum toxin injections. PMID:28049214

  17. 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

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

    PubMed

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

    1992-05-01

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

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

    PubMed Central

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

    2012-01-01

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

  20. 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

  1. Sensitivity to Pain Traumatization Scale: development, validation, and preliminary findings

    PubMed Central

    Katz, Joel; Fashler, Samantha R; Wicks, Claire; Pagé, M Gabrielle; Roosen, Kaley M; Kleiman, Valery; Clarke, Hance

    2017-01-01

    Background This article reports three studies describing the development and validation of the 12-item Sensitivity to Pain Traumatization Scale (SPTS-12). SPT refers to the anxiety-related cognitive, emotional, and behavioral reactions to pain that resemble the features of a traumatic stress reaction. Methods In Study 1, a preliminary set of 79 items was administered to 116 participants. The data were analyzed by using combined nonparametric and parametric item response theory resulting in a 12-item scale with a one-factor structure and good preliminary psychometric properties. Studies 2 and 3 assessed the factor structure and psychometric properties of the SPTS-12 in a community sample of 823 participants (268 with chronic pain and 555 pain-free) and a clinical sample of 345 patients (126 with chronic post-surgical pain, 92 with other nonsurgical chronic pain, and 127 with no chronic pain) at least 6 months after undergoing coronary artery bypass graft surgery, respectively. Results The final SPTS-12 derived from Study 1 comprised 12 items that discriminated between individuals with different levels of SPT, with the overall scale showing good to very good reliability and validity. The results from Studies 2 and 3 revealed a one-factor structure for chronic pain and pain-free samples, excellent reliability and concurrent validity, and moderate convergent and discriminant validity. Conclusion The results of the three studies provide preliminary evidence for the validity and reliability of the SPTS-12. PMID:28615962

  2. 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

  3. 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

  4. TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis.

    PubMed

    Lapointe, Tamia K; Basso, Lilian; Iftinca, Mircea C; Flynn, Robyn; Chapman, Kevin; Dietrich, Gilles; Vergnolle, Nathalie; Altier, Christophe

    2015-07-15

    Quiescent phases of inflammatory bowel disease (IBD) are often accompanied by chronic abdominal pain. Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive. This study aimed at establishing the role of TRPV1 in the peripheral sensitization underlying chronic visceral pain in the context of colitis. Wild-type and TRPV1-deficient mice were separated into three groups (control, acute colitis, and recovery), and experimental colitis was induced by oral administration of dextran sulfate sodium (DSS). Recovery mice showed increased chemically and mechanically evoked visceral hypersensitivity 5 wk post-DSS discontinuation, at which point inflammation had completely resolved. Significant changes in nonevoked pain-related behaviors could also be observed in these animals, indicative of persistent discomfort. These behavioral changes correlated with elevated colonic levels of substance P (SP) and TRPV1 in recovery mice, thus leading to the hypothesis that SP could sensitize TRPV1 function. In vitro experiments revealed that prolonged exposure to SP could indeed sensitize capsaicin-evoked currents in both cultured neurons and TRPV1-transfected human embryonic kidney (HEK) cells, a mechanism that involved TRPV1 ubiquitination and subsequent accumulation at the plasma membrane. Importantly, although TRPV1-deficient animals experienced similar disease severity and pain as wild-type mice in the acute phase of colitis, TRPV1 deletion prevented the development of postinflammatory visceral hypersensitivity and pain-associated behaviors. Collectively, our results suggest that chronic exposure of colon-innervating primary afferents to SP could sensitize TRPV1 and thus participate in the establishment of persistent abdominal pain following acute inflammation. Copyright © 2015 the American Physiological Society.

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Cold-induced limb pain decreases sensitivity to pressure-pain sensations in the ipsilateral forehead.

    PubMed

    Knudsen, Lone; Drummond, Peter D

    2009-11-01

    The aim of this study was to investigate the effect of unilateral limb pain on sensitivity to pain on each side of the forehead. In the first experiment, pressure-pain thresholds and sharpness sensations were assessed on each side of the forehead in 45 healthy volunteers before and after a 10 degrees C cold pressor of the hand and in 18 controls who were not subjected to the cold pressor. In a second experiment, forehead sensitivity was assessed in 32 healthy volunteers before and after a 2 degrees C cold pressor. The assessments were repeated without the cold pressor, and before and after six successive 4 degrees C cold pressor tests. The 10 degrees C cold pressor did not influence forehead sensitivity, whereas the 2 degrees C cold pressor and the 4 degrees C cold pressor tests resulted in bilateral analgesia to sharpness and pressure. The analgesia to pressure was greater in the ipsilateral forehead. Stress-induced analgesia and diffuse noxious inhibitory controls may have contributed to the analgesia to pressure-pain and sharpness sensations bilaterally after the most painful cold pressor tests. The locus coeruleus inhibits ipsilateral nociceptive activity in dorsal horn neurons during limb inflammation, and thus may have mediated the ipsilateral component of analgesia. Pain-evoked changes in forehead sensitivity differed for sharpness and pressure, possibly due to separate thalamic or cortical representations of cutaneous and deep tissue sensibility. These findings suggest that several mechanisms act concurrently to influence pain sensitivity at sites distant from a primary site of painful stimulation.

  8. Pain sensitivity is altered in animals after subchronic ketamine treatment.

    PubMed

    Becker, Axel; Grecksch, Gisela; Schröder, Helmut

    2006-12-01

    Clinical observations have shown that pain sensitivity is altered in some schizophrenic patients. To study alterations in pain sensitivity, the ketamine model in schizophrenia research was employed. Rats were subchronically injected with the dissociative anaesthetic ketamine (Ket, ten injections of 30 mg/kg, one injection per day over a period of 10 days). Two weeks after treatment completion, the animals' pain sensitivity was assayed in the hot plate test and they were subjected to electrical stimulation of the tail root. In addition, the effect of morphine was studied. In group-housed animals, there was no difference between Ket-injected animals and control rats as measured in both nociceptive tests. In singly housed Ket-injected rats, pain threshold was increased in the electrical stimulation test. This suggests that stress due to single housing might be essential for modifications of pain sensitivity. Moreover, the antinociceptive effect of morphine was modified after single housing. Interestingly, the effect of morphine on locomotor activity was similar in both groups. In group-housed rats, mu receptor binding was unchanged in the frontal cortex, whereas Ket-injected animals had decreased levels in the hippocampus. In singly housed animals, mu receptor binding in Ket-injected rats increased in the frontal cortex and decreased in the hippocampus. (35)S-GTPgamma-S binding increased in the frontal cortex in both singly housed groups, but remained unchanged in the hippocampus. The data suggest that the ketamine model might be useful for studying altered pain sensitivity in schizophrenia. Moreover, the data suggest that modifications in mu opioid receptor binding contribute to this phenomenon.

  9. Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving

    PubMed Central

    Ren, Zhen-Yu; Shi, Jie; Epstein, David H.; Wang, Jun; Lu, Lin

    2013-01-01

    Rationale Craving is a primary feature of opiate addiction and is clinically significant because of its potential to trigger opiate use and relapse. Opiate use can also produce abnormal pain perception. We predicted that for opiate addicts (OAs), there may be an association between these two major features of addiction (drug craving and abnormal pain responses). Objectives To examine pain responses in abstinent opiate addicts in comparison with healthy controls using a cold-pressor test (CPT) and investigate the correlations of cue-induced drug craving with pain responses. Material and methods Fifty-four abstinent OAs and 46 healthy subjects participated in the CPT, and the OAs were also exposed to heroin-related cues the day before the pain test. Outcome measures included pain-tolerance time, VAS ratings of pain intensity and distress, and (in the cue-exposure procedure) VAS ratings of heroin craving and anxiety. Results In the CPT, abstinent addicts showed shorter pain-tolerance time (85.1±14.1 s vs. 133.7±16.7 s, p<0.05) and higher ratings of pain distress (61±3.2 vs. 45.6±3.2, p< 0.01) compared to healthy controls. When we divided the addicts and controls into pain-sensitive (PS) and pain-tolerant (PT) groups by dichotomizing each group in terms of pain-tolerance time, we again found differences between the two PS groups (37.3±3.5 s vs. 57.4±5.1 s, p<0.01 for pain-tolerance time; 66.7±3.2 vs. 52.4±3.3, p<0.01 for distress ratings). For all participants, pain-tolerance time was negatively correlated with VAS ratings for pain intensity and distress. More importantly, the PS addicts reported greater cue-induced craving than the PT addicts (17.8±2.2 vs. 4.5±4.2, p<0.05). For the addict group as a whole, pain distress (the affective aspect of pain) was positively correlated with intensity of cue-induced craving measured on a different day (r=0.33, p=0.01). Conclusions A hyperalgesic state persists for at least 5 months in abstinent OAs and is predictive of

  10. Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving.

    PubMed

    Ren, Zhen-Yu; Shi, Jie; Epstein, David H; Wang, Jun; Lu, Lin

    2009-06-01

    Craving is a primary feature of opiate addiction and is clinically significant because of its potential to trigger opiate use and relapse. Opiate use can also produce abnormal pain perception. We predicted that for opiate addicts (OAs), there may be an association between these two major features of addiction (drug craving and abnormal pain responses). To examine pain responses in abstinent opiate addicts in comparison with healthy controls using a cold-pressor test (CPT) and investigate the correlations of cue-induced drug craving with pain responses. Fifty-four abstinent OAs and 46 healthy subjects participated in the CPT, and the OAs were also exposed to heroin-related cues the day before the pain test. Outcome measures included pain-tolerance time, VAS ratings of pain intensity and distress, and (in the cue-exposure procedure) VAS ratings of heroin craving and anxiety. In the CPT, abstinent addicts showed shorter pain-tolerance time (85.1 +/- 14.1 s vs. 133.7 +/- 16.7 s, p < 0.05) and higher ratings of pain distress (61 +/- 3.2 vs. 45.6 +/- 3.2, p < 0.01) compared to healthy controls. When we divided the addicts and controls into pain-sensitive (PS) and pain-tolerant (PT) groups by dichotomizing each group in terms of pain-tolerance time, we again found differences between the two PS groups (37.3 +/- 3.5 s vs. 57.4 +/- 5.1 s, p < 0.01 for pain-tolerance time; 66.7 +/- 3.2 vs. 52.4 +/- 3.3, p < 0.01 for distress ratings). For all participants, pain-tolerance time was negatively correlated with VAS ratings for pain intensity and distress. More importantly, the PS addicts reported greater cue-induced craving than the PT addicts (17.8 +/- 2.2 vs. 4.5 +/- 4.2, p < 0.05). For the addict group as a whole, pain distress (the affective aspect of pain) was positively correlated with intensity of cue-induced craving measured on a different day (r = 0.33, p = 0.01). A hyperalgesic state persists for at least 5 months in abstinent OAs and is predictive of cue

  11. 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.

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

    PubMed Central

    Li, Wing; Graham, Andrew D.

    2016-01-01

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

  13. Pain experiences of patients with musculoskeletal pain + central sensitization: A comparative Group Delphi Study

    PubMed Central

    Schäfer, Axel Georg Meender; Joos, Leonie Johanna; Roggemann, Katharina; Waldvogel-Röcker, Kerstin; Pfingsten, Michael; Petzke, Frank

    2017-01-01

    Objectives Central sensitization (CS) is regarded as an important contributing factor for chronification of musculoskeletal pain (MSP). It is crucial to identify CS, as targeted multimodal treatment may be indicated. The primary objective of this study was therefore to explore pain experience of individuals with MSP+CS in order to gain a better understanding of symptoms in relation to CS from a patient perspective. The secondary objective was to investigate whether pain experiences of patients with MSP+CS differ from those of individuals with neuropathic pain (NP). Methods We conducted a comparative Group Delphi Study including patients with MSP+CS and neuropathic pain (NP). 13 guiding questions were used to gather information about sensory discriminatory, affective and associated bodily, mental and emotional phenomena related to the pain experience of patients. Descriptions were categorized using qualitative content analysis. Additionally, patients completed several pain related questionnaires. Results Nine participants with MSP+CS and nine participants with NP participated. The Delphi procedure revealed three main themes: psycho-emotional factors, bodily factors and environmental factors. Descriptions of patients with MSP+CS showed a complex picture, psycho-emotional factors seem to have a considerable impact on pain provocation, aggravation and relief. Impairments associated with mental ability and psyche affected many aspects of daily life. In contrast, descriptions of patients with NP revealed a rather mechanistic and bodily oriented pain experience. Discussion Patients with MSP+CS reported distinct features in relation to their pain that were not captured with current questionnaires. Insight in patient’s pain experience may help to choose and develop appropriate diagnostic instruments. PMID:28796805

  14. Integrative approach to pain genetics identifies pain sensitivity loci across diseases.

    PubMed

    Ruau, David; Dudley, Joel T; Chen, Rong; Phillips, Nicholas G; Swan, Gary E; Lazzeroni, Laura C; Clark, J David; Butte, Atul J; Angst, Martin S

    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.

  15. Oxidation Sensitive Nociception Involved in Endometriosis Associated Pain

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-03-01

    Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu and is rich in inflammatory markers, pain-inducing prostaglandins prostaglandin E2 and prostaglandin F2α, and lipid peroxides; and the endometriotic tissue is innervated with nociceptors. Our clinical study showed that the abundance of oxidatively modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (1) the detection of lipoprotein-derived oxidation-sensitive pain molecules, (2) the ability of such molecules to induce nociception, and (3) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins to be similar to that seen in the PF. Oxidatively modified lipoproteins induced hypothermia (intracerebroventricular) in CD-1 mice and nociception in the Hargreaves paw withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin E and N-acetylcysteine, and the nonsteroidal anti-inflammatory drug indomethacin suppressed the pain-inducing ability of oxidatively modified lipoproteins. Treatment of human endometrial cells with oxidatively modified lipoproteins or PF from women with endometriosis showed upregulation of similar genes belonging to opioid and inflammatory pathways. Our finding that oxidatively modified lipoproteins can induce nociception has a broader impact not only on the treatment of endometriosis-associated pain but also on other diseases associated with chronic pain.

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

    PubMed Central

    Rowbotham, Michael C.; Dahl, Jørgen B.

    2013-01-01

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

  18. Pain sensitivity and healing of hot-iron cattle brands.

    PubMed

    Tucker, C B; Mintline, E M; Banuelos, J; Walker, K A; Hoar, B; Varga, A; Drake, D; Weary, D M

    2014-12-01

    Hot-iron branding is painful for cattle, but little is known about the duration of or effective methods to control this pain. This work quantified pain sensitivity and healing in branded and unbranded animals. In addition, the effects of a single injection of nonsteroidal anti-inflammatory drug (NSAID) were also considered; this has been suggested as practical method of mitigating pain in the hours after the procedure. Calves (mean±SE, 126±2.2 d and 112±2.8 kg) were hot-iron branded and allocated to 1 of 4 treatments: branded with or without flunixin meglumine (intravenous; 1.1 mg/kg) and unbranded with or without this NSAID (n=12/treatment). Pain sensitivity was assessed by applying a known and increasing force with a von Frey anesthesiometer in the center of the brand (or equivalent area in nonbranded treatments) until animals showed a behavioral response. Healing was measured with a 6-point scale (1=fresh brand and 6=no scabbing and fully repigmented). These measures, along with weight gain and surface temperature, were recorded 1, 2, 7, 14, 21, 28, 35, 42, 56, and 71 d after branding. Lying behavior was recorded with loggers from the day before to d 27 after branding. Brand wounds were more painful than nonbranded tissue (P<0.001). These differences were most pronounced in the days immediately after branding (e.g., d 7; 113±36 g of force for Brand vs. 449±23 g force for No brand, mean±SE) but persisted until d 71 (380±37 g force for Brand vs. 453±23 g of force for No brand, mean±SE); only 67% of brands were fully regimented or healed by this time. The first fully healed brand was identified 8 wk after the procedure. Giving a single injection of flunixin had no brand-specific effects on sensitivity, surface temperature, or healing but improved weight gain in the days after branding in all treated groups (flunixin×brand×day, P<0.001). Flunixin-treated animals also spent 0.7 h less time lying down on the day of branding but tended to spend more time

  19. Somatosensory sensitivity in patients with persistent idiopathic orofacial pain is associated with pain relief from hypnosis and relaxation.

    PubMed

    Baad-Hansen, Lene; Abrahamsen, Randi; Zachariae, Robert; List, Thomas; Svensson, Peter

    2013-06-01

    In a recent study hypnosis has been found to relieve persistent idiopathic orofacial pain. Quantitative sensory testing (QST) is widely used to evaluate somatosensory sensitivity, which has been suggested as a possible predictor of management outcome. The objectives of this study were to examine: (1) possible associations between clinical pain relief and baseline somatosensory sensitivity and (2) the effect of hypnosis management on QST parameters. Forty-one patients with persistent idiopathic orofacial pain completed this randomized controlled study in 1 of 2 groups: hypnosis (hypnotic analgesia suggestions) or control (relaxation). QST at 2 intraoral (pain region and contralateral mirror image region) and 3 extraoral (hand and both cheeks) sites was performed at baseline and after the hypnosis/control management, together with pressure pain thresholds and pressure pain tolerance thresholds determined bilaterally at the masseter and temporalis muscles, the temporomandibular joints, and the third finger. Degree of pain relief was negatively correlated with a summary statistic of baseline somatosensory sensitivity (summed z-score), that is, high baseline somatosensory sensitivity was associated with low pain relief (r=-0.372, P=0.020). Hypnosis had no major effect on any QST measure compared with relaxation (P>0.063). High pain sensitivity at baseline may predict poor pain management outcome. In addition, despite clear clinical pain relief, hypnosis did not significantly or specifically influence somatosensory sensitivity. Future studies should further explore QST measures as possible predictors of different management response in orofacial pain conditions.

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

    PubMed

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

    2017-01-01

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

  1. Assessment of postsurgical distress and pain in laboratory mice by nest complexity scoring.

    PubMed

    Jirkof, Paulin; Fleischmann, Thea; Cesarovic, Nikola; Rettich, Andreas; Vogel, Johannes; Arras, Margarete

    2013-07-01

    Preliminary studies have suggested a correlation between postsurgical pain and nest building behaviour in laboratory mice. However, there is no standardized measure for estimating pain by means of nest building performance. Here, we investigated nest building under various conditions, and scored nest complexity to assess postsurgical pain. Mice of both sexes, different strains [C57BL/6J, DBA/2J, and B6D2-Tg(Pr-mSMalphaActin)V5rCLR-25], and kept under different housing conditions, showed no differences in their latency to use the offered nest material. Healthy female C57BL/6J mice were engaged 4.3% of the day with nest building and showed three peaks of this behaviour: in the beginning and middle of the light phase, and in the second half of the dark phase. For assessment of postsurgical pain, female C57BL/6J mice underwent a sham embryo transfer +/− different doses of the analgesic carprofen or control treatment. Nest complexity scoring at 9 h after the experimental treatments (i.e. at the end of the light phase) resulted in less than 10% of animals with noticeably manipulated nest material (nestlet) after surgery and more than 75% of healthy mice having built identifiable-to-complex nests or had noticeably manipulated nestlets, while animals after anaesthesia-only showed intermediate nest complexity. Carprofen analgesia resulted in no (5 mg/kg) or only slight (50 mg/kg) improvement of nest complexity after surgery. Thus, nest complexity scoring can be incorporated into daily laboratory routine and can be used in mice as a sensitive tool for detecting reduced wellbeing and general condition, but probably not for determining the efficacy of pain treatment.

  2. 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.

  3. 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.

  4. A unique association between cognitive inhibition and pain sensitivity in healthy participants.

    PubMed

    Oosterman, Joukje M; Dijkerman, H Chris; Kessels, Roy P C; Scherder, Erik J A

    2010-11-01

    The experience of pain constitutes a complex phenomenon that is determined by and reflects the interplay of many factors, including cognitive functions. Little is known, however, about the precise role of executive functions in pain sensitivity. Importantly, these functions may be directly related to the ability to control pain. The present study evaluated the relationship between pain sensitivity and executive functions in a sample of healthy volunteers. Pain sensitivity was assessed with the cold pressor test. The immersion time, here defined as the time until substantial pain was reported, was measured. Additional pain intensity and pain unpleasantness ratings were obtained as an indication of pain experience. The results revealed a unique association between cognitive inhibition (i.e. the Stroop interference score), but not other executive functions, and immersion time, pain intensity, and pain unpleasantness. Specifically, better cognitive inhibition was related to a reduction in pain sensitivity as evident by an increased immersion time and decreased pain intensity and pain unpleasantness ratings. As such, cognitive inhibition may be an important determinant of pain sensitivity. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  5. Biological and psychological predictors of visceral pain sensitivity in healthy premenopausal women.

    PubMed

    Lacourt, T E; Houtveen, J H; Doornen, L J P; Benson, S; Grigoleit, J-S; Cesko, E; Elsenbruch, S

    2014-04-01

    Factors that are associated with pain perception remain incompletely understood, especially in the visceral pain field. Therefore, the current study aimed to investigate possible psychological and biological predictors of visceral pain sensitivity in healthy subjects. In a sample of 59 healthy premenopausal female subjects on hormonal contraceptives, measures of gastrointestinal (GI) symptoms in daily life, trait and state anxiety, depression, serum cortisol concentrations and serum levels of interleukin-6 (IL-6) were obtained, followed by assessment of rectal distension pain sensitivity measures (i.e., rectal distension sensory threshold, pain threshold and pain ratings for discrete rectal distension stimuli). Regression analyses showed that more GI symptoms in daily life predicted a lower pain threshold. Higher levels of state anxiety predicted a lower pain threshold. Higher cortisol concentrations predicted lower pain ratings. IL-6 was positively related to GI symptoms but was a non-significant predictor of pain threshold in the multiple regression analysis. Similar to findings in patients with functional GI symptoms, we showed that subclinical GI symptoms predict visceral pain sensitivity. In line with somatic pain findings, state but not trait anxiety was found to predict visceral pain sensitivity. Our finding on serum cortisol as positive predictor of pain sensitivity might be interpreted in light of immunosuppressive effects of cortisol. Our finding on the role of IL-6 in GI symptoms is promising for understanding GI complaints in patients and needs further investigation. © 2013 European Pain Federation - EFIC®

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

    PubMed

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

    2017-06-01

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

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

    PubMed

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

    2015-07-01

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

  8. Widespread pressure pain hypersensitivity in patients with multiple sclerosis with and without pain as sign of central sensitization.

    PubMed

    Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Ortíz-Gutiérrez, Rosa; Caminero, Ana B; Salom-Moreno, Jaime; Arendt-Nielsen, Lars

    2015-01-01

    To determine the presence of widespread pressure hyperalgesia in multiple sclerosis (MS) patients with and without pain and its association with pain and fatigue. A total of 108 individuals with definite MS, 49 men and 59 women (mean age, 44±8 y) and 108 age-matched and sex-matched pain-free controls (mean age, 44±9 y) were included. Fifty patients (n=58, 54%) reported pain and 50 (46%) did not. Pressure pain threshold (PPT) was bilaterally assessed over supraorbital, infraorbital, mental, median, radial and ulnar nerve trunks, C5-C6 joint, second metacarpal, and tibialis anterior muscle by an assessor blinded to the patient's condition. The intensity of pain was assessed with a numerical pain rate scale (0 to 10), fatigue was determined with the Fatigue Impact Scale, and depression was evaluated with the Beck Depression Inventory. The analyses of covariance revealed that PPT were significantly decreased bilaterally over the supraorbital, infraorbital, mental, median, ulnar and radial nerve trunks, C5-C6 joint, second metacarpal, and tibialis anterior muscles in patients with MS compared with pain-free controls (all, P<0.001). No significant differences existed between MS patients with pain and those without pain (all P>0.944). Patients with pain exhibited higher fatigue and depression than those patients without pain (P<0.05). PPT was not associated with any clinical variable, that is, pain, depression, or fatigue. Our study found widespread pressure pain hyperalgesia in individuals with MS as compared with pain-free controls. No differences existed between MS patients with pain and those without pain in the presence of widespread pressure sensitivity. Current results suggest that MS is associated with sensory hyperexcitability of the central nervous system or dysfunction in endogenous pain modulatory systems.

  9. Pain and motor control: From the laboratory to rehabilitation.

    PubMed

    Hodges, Paul W

    2011-04-01

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

  10. Reliable Digit Span is Unaffected by Laboratory-Induced Pain

    ERIC Educational Resources Information Center

    Etherton, Joseph L.; Bianchini, Kevin J.; Ciota, Megan A.; Greve, Kevin W.

    2005-01-01

    Reliable Digit Span (RDS) is an indicator used to assess the validity of cognitive test performance. Scores of 7 or lower suggest poor effort or negative response bias. The possibility that RDS scores are also affected by pain has not been addressed thus potentially threatening RDS specificity. The current study used cold pressor-induced pain to…

  11. High pain sensitivity is distinct from high susceptibility to non-painful sensory input at threshold level.

    PubMed

    Hummel, Thomas; Springborn, Maria; Croy, Ilona; Kaiser, Jochen; Lötsch, Jörn

    2011-04-01

    Individuals may differ considerably in their sensitivity towards various painful stimuli supporting the notion of a person as stoical or complaining about pain. Molecular and functional imaging research provides support that this may extend also to other sensory qualities. Whether a person can be characterized as possessing a generally high or low sensory acuity is unknown. This was therefore assessed with thresholds to painful and non-painful stimuli, with a focus on chemical stimuli that besides pain may evoke clearly non-painful sensations such as taste or smell. In 36 healthy men and 78 women (ages 18 to 52 years), pain thresholds to chemo-somatosensory (intranasal gaseous CO(2)) and electrical stimuli (cutaneous stimulation) were significantly correlated (ρ(2)=0.2268, p<0.001). Two clusters separated persons with either high (n=72) or low (n=22) pain sensitivity. However, the correlation did not extend to non-painful stimuli of other sensory qualities, i.e., for the rose-like odor phenyl ethyl alcohol and gustatory thresholds for sour (citric acid) and salty (NaCl). Similarly, pain clusters showed no differences in thresholds to other stimuli. Moreover, no clustering was obtained for thresholds to both painful and non-painful stimuli together. Thus, individuals could not be characterized as highly sensitive (or insensitive) to all chemical stimuli no matter of evoking pain. This suggests that pain is primarily a singular sensory perception distinct from others such as olfaction or taste. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  13. In Vivo praying and catastrophizing mediate the race differences in experimental pain sensitivity.

    PubMed

    Meints, Samantha M; Hirsh, Adam T

    2015-05-01

    Black individuals have a lower tolerance for experimental pain than white individuals. Black and white individuals also differ in their use of pain coping strategies, which may explain the race differences in pain sensitivity. We examined the extent to which situation-specific pain coping mediated black-white differences in pain sensitivity. We hypothesized that 1) black participants would demonstrate lower pain tolerance than white participants, 2) black participants would use different pain coping strategies than white participants, and 3) the differential use of these strategies would mediate the relationship between race and pain tolerance. Healthy college undergraduates (N = 190) participated in a cold pressor task and then completed the Coping Strategies Questionnaire-Revised to assess their situation-specific pain coping. Compared with white participants, black participants demonstrated lower pain tolerance, engaged in more situation-specific catastrophizing and praying, and ignored pain less frequently. Catastrophizing and praying were inversely related to pain tolerance and were significant mediators of the relationship between race and pain tolerance. The indirect effect of praying was stronger than that of catastrophizing. Race differences in pain sensitivity may be due, in part, to differences in the use of catastrophizing and praying as coping strategies. These results may help guide treatments addressing maladaptive pain coping. This study suggests that race differences in pain sensitivity may be due, in part, to the differential use of catastrophizing and praying strategies. Psychosocial treatments for pain should encourage patients to take an active role in their pain management. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  14. Spinal manipulative therapy-specific changes in pain sensitivity in individuals with low back pain (NCT01168999).

    PubMed

    Bialosky, Joel E; George, Steven Z; Horn, Maggie E; Price, Donald D; Staud, Roland; Robinson, Michael E

    2014-02-01

    Spinal manipulative therapy (SMT) is effective for some individuals experiencing low back pain; 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 low back pain 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 2 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 2 weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (P = .05, partial η(2) = .07). Group-dependent differences were not observed for changes in pain intensity and disability at 2 weeks. Participant satisfaction was greatest following the enhanced placebo SMT. This study was registered at www.clinicaltrials.gov under the identifier NCT01168999. The results of this study indicate attenuation of pain sensitivity is greater in response to SMT than the expectation of receiving an SMT. These findings suggest a potential mechanism of SMT related to lessening of central sensitization and may indicate a preclinical effect beyond the expectations of receiving SMT. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2008-10-15

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

  16. The Mu Opioid Receptor A118G Gene Polymorphism Moderates Effects of Trait Anger-Out on Acute Pain Sensitivity

    PubMed Central

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

    2008-01-01

    Both trait anger-in (managing anger through suppression) and anger-out (managing anger through direct expression) are related to pain responsiveness, but only anger-out effects involve opioid mechanisms. Preliminary work suggested the effects of anger-out on post-operative analgesic requirements were moderated by the A118G single nucleotide polymorphism of the mu opioid receptor gene. This study further explored these potential genotype X phenotype interactions as they impact acute pain sensitivity. Genetic samples and measures of anger-in and anger-out were obtained in 87 subjects (from three studies) who participated in controlled laboratory acute pain tasks (ischemic, finger pressure, thermal). McGill Pain Questionnaire (MPQ) Sensory and Affective ratings for each pain task were standardized within studies, aggregated across pain tasks, and combined for analyses. Significant anger-out X A118G interactions were observed (p’s<.05). Simple effects tests for both pain measures revealed that whereas anger-out was nonsignificantly hyperalgesic in subjects homozygous for the wild-type allele, anger-out was significantly hypoalgesic in those with the variant G allele (p’s<.05). For the MPQ-Affective measure, this interaction arose both from low pain sensitivity in high anger-out subjects with the G allele and heightened pain sensitivity in low anger-out subjects with the G allele relative to responses in homozygous wild-type subjects. No genetic moderation was observed for anger-in, although significant main effects on MPQ-Affective ratings were noted (p<.005). Anger-in main effects were due to overlap with negative affect, but anger-out X A118G interactions were not, suggesting unique effects of expressive anger regulation. Results support opioid-related genotype X phenotype interactions involving trait anger-out. PMID:18579306

  17. Do fundamental fears differentially contribute to pain-related fear and pain catastrophizing? An evaluation of the sensitivity index.

    PubMed

    Vancleef, Linda M G; Peters, Madelon L; Roelofs, Jeffrey; Asmundson, Gordon J G

    2006-08-01

    Three fundamental fears - anxiety sensitivity (AS), injury/illness sensitivity (IS) and fear of negative evaluation (FNE) - have been proposed to underlie common fears and psychopathological conditions. In pain research, the relation between AS and (chronic) pain processes was the subject of several studies, whereas the possible role of IS has been ignored. The current research examines the role of IS with respect to various pain-related variables in two studies. In the first study, 192 healthy college students completed the Sensitivity Index (SI; a composite measure assessing the three fundamental fears) and various pain-related questionnaires. In a second study, 60 students out of the original sample took part in a pain induction procedure and completed the SI as well. We first examined the properties of the SI. Factor analysis on the SI replicated the proposed factor structure [Taylor S. The structure of fundamental fears, J Behav Ther Exp Psychiat 1993;24:289-99]. However, some items of the ASI did show problematic loadings and were therefore excluded in subsequent analyses. The main hypothesis of the current study states that IS is a stronger predictor than AS of pain catastrophizing and fear of pain as assessed by self-report measures, and of pain tolerance and anticipatory fear of pain as assessed in a pain induction study. This hypothesis could be confirmed for all variables, except for pain tolerance, which was not predicted by any of the three fundamental fears. The current study can be considered as an impetus for devoting attention to IS in future pain research.

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

    PubMed

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

    2015-05-01

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

  19. The relationship between resting blood pressure and acute pain sensitivity: effects of chronic pain and alpha-2 adrenergic blockade.

    PubMed

    Bruehl, Stephen; Chung, Ok Y; Diedrich, Laura; Diedrich, André; Robertson, David

    2008-02-01

    This study tested for alpha-2 adrenergic mediation of the inverse relationship between resting blood pressure and acute pain sensitivity in healthy individuals. It also replicated limited prior work suggesting this inverse blood pressure/pain association is altered in chronic pain, and provided the first test of whether chronic pain-related changes in alpha-2 adrenergic function contribute to these alterations. Resting blood pressure was assessed in 32 healthy controls and 24 chronic low back pain participants prior to receiving placebo or an intravenous alpha-2 adrenergic receptor antagonist (yohimbine hydrochloride, 0.4 mg/kg) in a randomized crossover design. Participants experienced three acute pain tasks during both sessions. A significant Systolic Blood Pressure x Participant Type x Drug interaction on finger pressure McGill Pain Questionnaire-Sensory ratings (P < .05) reflected significant hyperalgesic effects of yohimbine in chronic pain participants with lower systolic blood pressures (P < .05) but not those with higher systolic pressures, and no significant effects of yohimbine in controls regardless of blood pressure level. A Drug x Systolic Blood Pressure interaction on finger pressure visual analog scale unpleasantness indicated the inverse blood pressure/pain association was significantly stronger under yohimbine relative to placebo (P < .05). Significant Participant Type x Systolic Blood Pressure interactions (P's < .05) were noted for finger pressure visual analog scale pain intensity and unpleasantness, ischemic pain threshold, and heat pain threshold, reflecting absence or reversal of inverse blood pressure/pain associations in chronic pain participants. Results suggest that blood pressure-related hypoalgesia can occur even when alpha-2 adrenergic systems are blocked. The possibility of upregulated alpha-2 adrenergic inhibitory function in chronic pain patients with lower blood pressure warrants further evaluation.

  20. Neuropathic pain assessment: update on laboratory diagnostic tools.

    PubMed

    Mainka, Tina; Maier, Christoph; Enax-Krumova, Elena K

    2015-10-01

    The purpose of this review was to provide an update on the diagnostic tools for neuropathic pain for clinical practice. The new definition of neuropathic pain by the International Association for the Study of Pain requires confirmation of a lesion or disease affecting the somatosensory system. In addition to traditional diagnostic procedures, for example, nerve conduction studies, skin biopsies depict morphological alteration and/or rarefication of the small intraepidermal nerve fibers and were recently used to identify small fiber abnormalities, for example, in patients with fibromyalgia or sarcoidosis. Quantitative sensory testing assesses the somatosensory function including both peripheral and central pathways. A recent consensus statement discussed its diagnostic value. Corneal confocal microscopy is a noninvasive method enabling in-vivo assessment of the small nerve fibers in the cornea and also seems to identify patients at risk for developing diabetic neuropathy at an early stage and to reflect the improvement of neuropathy after treatment. Further promising methods are the microneurography and nociceptive evoked potentials; however, they are technically challenging and their diagnostic value for clinical practice has yet to be confirmed. For diagnosing neuropathic pain, confirmation of a lesion or disease affecting the somatosensory system is needed. Better clinical phenotyping will hopefully enable individualized mechanism-based treatment of neuropathic pain.

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

    PubMed

    Vaegter, Henrik B; Graven-Nielsen, Thomas

    2016-07-01

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

  2. Increased spinal pain sensitization in major depressive disorder: A pilot study.

    PubMed

    Tikàsz, Andràs; Tourjman, Valérie; Chalaye, Philippe; Marchand, Serge; Potvin, Stéphane

    2016-12-30

    Although patients suffering from major depressive disorder (MDD) often complain from painful symptoms, the relationship between experimental pain processes and depression has yet to be clearly characterized. Only recently have studies employing temporal summation (TS) paradigms offered preliminary insight into the co-occurrence of pain and depression. This study sets out to evaluate the contribution of spinal and supraspinal processes in pain sensitization in MDD using a TS paradigm. Thirteen volunteers with no psychiatric disorders (controls) and fourteen MDD subjects were included in the analysis. Low-(0.14Hz) and high-(1Hz) frequency intermittent stimulations of the sural nerve were used to induce TS. Spinal pain sensitization was quantified by measuring the change in the amplitude of the nociceptive-specific flexion reflex (NFR) response, and supraspinal pain sensitization was obtained by measuring change in subjective pain rating, from the low- to high-frequency stimulation condition. We found an increased sensitization in the NFR response (p<0.05) in MDD subjects in the high-frequency condition, which did not translate into an increase of their subjective responses. However, we found a positive association between spinal sensitization and painful somatic symptoms in MDD subjects. Together, these results suggest increased spinal pain sensitization in MDD, which might explain the high prevalence of painful somatic symptoms in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-08-01

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

  7. Long-term effects of early exposure to stress, pain, opioids and anaesthetics on pain sensitivity and neurocognition.

    PubMed

    van den Bosch, Gerbrich E; van Dijk, Monique; Tibboel, Dick; de Graaff, Jurgen C

    2017-09-26

    Background Experimental studies have shown that neonatal exposure to stress, pain, opioids and anaesthetics may cause histologic and morphologic changes in the central nervous system with associated functional and behavioural changes in the long term. An important question is whether this holds true for humans also - and in particular for sick neonates who often are exposed to pain and receive anaesthetics and sedatives. Methods In this narrative review, we evaluate the effects of neonatal exposure to stress, pain, opioids and anaesthetics in infancy and childhood in animals and in preterm born and term born humans on pain sensitivity, brain morphology, cognition and behaviour later in life. Results In animals, neonatal exposure to stress, pain, opioids and early exposure to anaesthetics are associated with neurodegeneration and cognitive problems later in life. Human studies mainly focus on pain sensitivity, cognition and behaviour and find contradictory outcomes. Dramatic long-term effects found in animal studies could not be confirmed in human. Conclusion While studies in animals suggest neurotoxic effects of early exposure to stress, pain, opioids and anaesthetics, these effects seem clinically less relevant in humans. A possible reason is that the latter often receive opioids in the presence of pain and opioids and anaesthetics in balanced therapeutic dosages and with adequate monitoring of physiological parameters, in contrast to animal studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed

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

    2016-01-01

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

  9. Catastrophizing and pain sensitivity among chronic pain patients: moderating effects of sensory and affect focus.

    PubMed

    Michael, Elizabeth S; Burns, John W

    2004-06-01

    Pain catastrophizing is a particularly harmful cognitive factor among patients with chronic pain, but little is known of mechanisms linking this factor to pain and disability. The study examined whether attentional focus on sensory versus affective information about pain constitutes a pathway by which catastrophizing affects responses to painful stimuli. Participants were 82 chronic pain patients assigned randomly to sensory focus, affect focus, or control conditions. They underwent cold pressors first prior to and then following an information focus manipulation, and they completed the Pain Catastrophizing Scale (PCS). Regressions produced significant Condition x PCS interaction effects on threshold and tolerance change from first to second cold pressor, such that PCS scores were significantly and negatively related to these changes in both sensory and affect focus conditions, but not in the control condition. Only a main effect for PCS scores emerged for self-reported pain changes. Solving regression equations for hypothetical PCS values (+- 1 SD from the mean) revealed that (a) high catastrophizers decreased threshold and tolerance in the affect focus condition and showed no appreciable changes in sensory focus and (b) low catastrophziers showed increases in threshold and tolerance in sensory focus, but no appreciable changes in affect focus. Further, the degree to which patients focused on emotions during pain partly mediated effects of PCS scores on threshold and tolerance changes. Catastrophizing about pain may affect pain severity and distress of chronic pain patients through a bias toward processing the most disturbing elements of a painful stimulus.

  10. Investigating the effects of anxiety sensitivity and coping on the perception of cold pressor pain in healthy women.

    PubMed

    Keogh, E; Mansoor, L

    2001-01-01

    Research indicates that anxiety sensitivity may be related to the negative experience of pain, especially amongst women. Further evidence with chronic pain patients indicates that anxiety sensitivity may result in avoidance pain-coping strategies. However, this effect has not yet been experimentally investigated in healthy groups. Therefore, the current study sought to investigate the effect of anxiety sensitivity and coping on women's responses to pain. Thirty women who were classified as high in anxiety sensitivity and 30 women classified as low in anxiety sensitivity participated. Within each anxiety sensitivity group, half the participants (n = 15) were randomly instructed to either focus on or avoid cold pressor pain sensations. As expected, women high in anxiety sensitivity were found to report higher levels of sensory and affective pain. Also, and consistent with previous research into anxiety sensitivity, no differences were found between anxiety sensitivity groups for measures of pain threshold or pain tolerance. The pain coping instruction manipulation was found to moderate pain experience, in that the avoidance strategy resulted in higher pain ratings compared to when instructed to focus. Finally, high anxiety sensitive women reported greater pain when instructed to avoid rather than focus on cold pressor pain. These results are discussed in light of previous research and future directions for pain management. Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.

  11. Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain.

    PubMed

    Koltzenburg, M; Torebjörk, H E; Wahren, L K

    1994-06-01

    Brush-evoked pain (mechanical allodynia, dynamic mechanical hyperalgesia) is a hallmark of neuropathic and inflammatory pain states. Here we have examined the neural mechanisms that induce and maintain this component of mechanical hyperalgesia. The principle finding of these experiments is that the severity of brush-evoked pain correlates with the intensity of background pain in patients suffering from chronic painful neuropathies and in normal subjects with acute experimental chemogenic pain. In experiments on nine normal subjects topical application of mustard oil for 5 min evoked strong burning pain and hyperalgesia to light mechanical stimuli. Differential nerve blocks (by compression of the superficial radial nerve) revealed that the brush-evoked pain was transmitted by A beta-fibres, which normally encode non-painful tactile sensations, while the burning pain was signalled by C-fibres. Psychophysical measurements showed that mustard oil treatment resulted in a pronounced sensitization of nociceptors to heat so that subsequent innocuous changes of skin temperature from 35 to 40 degrees C resulted in a proportional increase of burning background pain. Changes in the magnitude of ongoing burning pain were closely correlated (r = 0.81) to the intensity of brush-evoked pain. While conduction block of A-fibres eliminated only touch-evoked pain, blockade of C-fibre excitation instantaneously abolished both ongoing and touch-evoked pain. In nine patients with chronic neuralgia (15 years mean duration) ongoing and brush-evoked pain were examined. In six patients, differential block of A beta-fibres eliminated touch-evoked pain, but ongoing pain persisted when only C-fibres were conducting. Complete relief of both ongoing and stimulus-induced pain was obtained in two patients with intravenous regional guanethedine block and in two other individuals by local anaesthetic blocks of nerves supplying the symptomatic skin, indicating that input from primary afferents was

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

    Allely, C. S.

    2013-01-01

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

  15. 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.

  16. 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

  17. 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.

  18. [Empathy for pain: A novel bio-psychosocial-behavioral laboratory animal model].

    PubMed

    Chen, Jun; Li, Zhen; Lv, Yun-Fei; Li, Chun-Li; Wang, Yan; Wang, Rui-Rui; Geng, Kai-Wen; He, Ting

    2015-12-25

    Empathy, a basic prosocial behavior, is referred to as an ability to understand and share others' emotional state. Generally, empathy is also a social-behavioral basis of altruism. In contrast, impairment of empathy development may be associated with autism, narcissism, alexithymia, personality disorder, schizophrenia and depression. Thus, study of the brain mechanisms of empathy has great importance to not only scientific and clinical advances but also social harmony. However, research on empathy has long been avoided due to the fact that it has been considered as a distinct feature of human beings from animals, leading to paucity of knowledge in the field. In 2006, a Canadian group from McGill University found that a mouse in pain could be shared by its paired cagemate, but not a paired stranger, showing decreased pain threshold and increased pain responses through emotional contagion while they were socially interacting. In 2014, we further found that a rat in pain could also be shared by its paired cagemate 30 min after social interaction, showing long-term decreased pain threshold and increased pain responses, suggesting persistence of empathy for pain (empathic memory). We also mapped out that the medial prefrontal cortex, including the anterior cingulate cortex, prelimbic cortex and infralimbic cortex, is involved in empathy for pain in rats, suggesting that a neural network may be associated with development of pain empathy in the CNS. In the present brief review, we give a brief outline of the advances and challenges in study of empathy for pain in humans and animals, and try to provide a novel bio-psychosocial-behavioral model for study of pain and its emotional comorbidity using laboratory animals.

  19. Topographical mapping and mechanical pain sensitivity of myofascial trigger points in the infraspinatus muscle.

    PubMed

    Ge, Hong-You; Fernández-de-Las-Peñas, César; Madeleine, Pascal; Arendt-Nielsen, Lars

    2008-10-01

    To screen for the presence of latent and active myofascial trigger points (MTrPs) in patients with unilateral shoulder and arm pain and perform topographical mapping of mechanical pain sensitivity bilaterally in the infraspinatus muscles. Nineteen patients with unilateral musculoskeletal shoulder pain participated in the study. The area overlying the infraspinatus on each side was divided into 10 adjacent sub-areas of 1cm(2), corresponding to the area of a pressure algometer probe. Pressure pain threshold (PPT) was measured in each sub-area bilaterally in the infraspinatus muscles. Following PPT measurement, an acupuncture needle was inserted into each sub-area five times in different directions in order to induce local twitch response and/or referred pain. A significantly lower PPT level in the infraspinatus muscle was detected on the painful side compared with the non-painful side (P=0.001). PPT at midfiber region of the infraspinatus muscles was lower than that at other muscle parts (P<0.05). Multiple, but not single, active MTrPs were found in the infraspinatus muscle on the painful side and there were also multiple latent MTrPs bilaterally in the infraspinatus muscles. PPT at active MTrPs was much lower than the latent MTrPs and again lower than the non-MTrPs. There exists bilateral mechanical hyperalgesia in patients with unilateral shoulder pain. Further, the association of multiple active MTrPs with unilateral shoulder pain and the heterogeneity of mechanical pain sensitivity distribution suggest a crucial role of peripheral sensitization in chronic myofascial pain conditions. Additionally, the locations of MTrPs identified with dry needling correspond well to PPT topographical mapping, suggesting that dry needling and PPT topographical mapping are sensitive techniques in the identification of MTrPs.

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

    PubMed

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

    2011-01-01

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

  1. Decreased alertness due to sleep loss increases pain sensitivity in mice.

    PubMed

    Alexandre, Chloe; Latremoliere, Alban; Ferreira, Ashley; Miracca, Giulia; Yamamoto, Mihoko; Scammell, Thomas E; Woolf, Clifford J

    2017-06-01

    Extended daytime and nighttime activities are major contributors to the growing sleep deficiency epidemic, as is the high prevalence of sleep disorders like insomnia. The consequences of chronic insufficient sleep for health remain uncertain. Sleep quality and duration predict presence of pain the next day in healthy subjects, suggesting that sleep disturbances alone may worsen pain, and experimental sleep deprivation in humans supports this claim. 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.

  2. Pain sensitivity of children with Down syndrome and their siblings: quantitative sensory testing versus parental reports.

    PubMed

    Valkenburg, Abraham J; Tibboel, Dick; van Dijk, Monique

    2015-11-01

    The aim of this study was to compare thermal detection and pain thresholds in children with Down syndrome with those of their siblings. Sensory detection and pain thresholds were assessed in children with Down syndrome and their siblings using quantitative testing methods. Parental questionnaires addressing developmental age, pain coping, pain behaviour, and chronic pain were also utilized. Forty-two children with Down syndrome (mean age 12y 10mo) and 24 siblings (mean age 15y) participated in this observational study. The different sensory tests proved feasible in 13 to 29 (33-88%) of the children with Down syndrome. These children were less sensitive to cold and warmth than their siblings, but only when measured with a reaction time-dependent method, and not with a reaction time-independent method. Children with Down syndrome were more sensitive to heat pain, and only 6 (14%) of them were able to adequately self-report pain, compared with 22 (92%) of siblings (p<0.001). Children with Down syndrome will remain dependent on pain assessment by proxy, since self-reporting is not adequate. Parents believe that their children with Down syndrome are less sensitive to pain than their siblings, but this was not confirmed by quantitative sensory testing. © 2015 Mac Keith Press.

  3. 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

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

    PubMed

    Shukla, M; Quirion, R; Ma, W

    2013-10-10

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

  5. Body mass index and distribution of body fat can influence sensory detection and pain sensitivity.

    PubMed

    Tashani, O A; Astita, R; Sharp, D; Johnson, M I

    2017-08-01

    The aim of this study was to investigate the influence of body fat percentage and its distribution on sensory detection and pain sensitivity responses to experimentally induced noxious stimuli in otherwise pain-free individuals. Seventy-two participants were divided into three equal groups according to their body mass index (BMI: normal, overweight and obese). Percentage body fat was estimated using a four-site skinfold method. Measurements of cold pressor pain threshold, tolerance and intensity; contact thermal sensory detection and heat pain threshold and tolerance (TSA-II - NeuroSensory Analyzer, Medoc); and blunt pressure pain threshold (algometer, Somedic SenseLab AB) were taken at the waist and thenar eminence. Mean ± SD pressure pain threshold of the obese group (620.72 ± 423.81 kPa) was significantly lower than normal (1154.70 ± 847.18 kPa) and overweight (1285.14 ± 998.89 kPa) groups. Repeated measures ANOVA found significant effects for site for cold detection threshold (F1,68  = 8.3, p = 0.005) and warm detection threshold (F1,68  = 38.69, p = 0.001) with waist having lower sensory detection thresholds than thenar eminence. For heat pain threshold, there were significant effects for site (F1,68  = 4.868, p = 0.031) which was lower for waist compared with thenar eminence (mean difference = 0.89 °C). Obese individuals were more sensitive than non-obese individuals to pressure pain but not to thermal pain. Body sites may vary in their response to different types and intensities of stimuli. The inconsistency of findings within and between research studies should catalyse further research in this field. This study provided evidence that body mass index and distribution of body fat can influence sensory detection and pain sensitivity. Obese individuals were more sensitive than normal range body mass index individuals to pressure pain but not to thermal pain. Pain response varied according to subcutaneous body fat at different body

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2016-10-01

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

  8. 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

  9. Perceived Pain Extent is Not associated with Widespread Pressure Pain Sensitivity, Clinical Features, Related-Disability, Anxiety, or Depression in Women with Episodic Migraine.

    PubMed

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

    2017-07-20

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

  10. 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

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

    PubMed

    Tuboly, Gábor; Horváth, Gyöngyi

    2009-05-30

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

  12. 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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. 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.

  16. 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

  17. Pressure Pain Sensitivity Maps of the Neck-Shoulder Region in Breast Cancer Survivors.

    PubMed

    Caro-Morán, Elena; Fernández-Lao, Carolina; Díaz-Rodríguez, Lourdes; Cantarero-Villanueva, Irene; Madeleine, Pascal; Arroyo-Morales, Manuel

    2016-10-01

    The aim of the present study was to report pressure pain sensitivity topographical maps of the frontal and dorsal parts of the shoulder region, and locate the pressure pain sensitive areas in breast cancer survivors compared with matched healthy control subjects. Twenty-two breast cancer survivors (BCS) and 22 matched control subjects participated. A numeric pain rating scale of the neck-shoulder area and pressure pain thresholds (PPTs) was assessed bilaterally over 28 points in the frontal and dorsal neck-shoulder area. Topographical pain sensitivity maps of the upper trapezius, pectoral, and anterior deltoid areas were computed. A three-way analysis of variance was carried out to evaluate the differences in PPTs. The BCS reported spontaneous neck pain (mean ± SD 3.6 ± 2.8), pain in the affected shoulder (4.3 ± 2.7), and pain in the non-affected shoulder (0.9 ± 1.8). Additionally, the BCS exhibited bilaterally lower PPTs in all the measurement points as compared with the control subjects (P < 0.05). The PPTs were lower at the superior part of the trapezius muscle (P < 0.001), the musculotendinous insertion, the anterior part of the deltoid muscle (P < 0.001), and the tendon of the pectoral muscle (P < 0.001) as compared with the control subjects. The results suggest the sensitization processes in the BCS and give preliminary evidence to most sensitive areas in the superior part of the upper trapezius and musculotendinous insertion of the pectoral muscle. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2015-04-01

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

  19. Individual differences in morphine and butorphanol analgesia: a laboratory pain study.

    PubMed

    Sibille, Kimberly T; Kindler, Lindsay L; Glover, Toni L; Gonzalez, Ricardo D; Staud, Roland; Riley, Joseph L; Fillingim, Roger B

    2011-07-01

    Responses to opioid analgesics are highly variable, and the understanding of contributing factors is limited. This laboratory study was designed to examine the contributions of sex and race to inter-individual variability in response to opioids. A randomized, double-blind, mixed design was implemented in the evaluation of analgesic response to a µ-opioid agonist and mixed agonist-antagonist, using three well-validated experimental pain assays (thermal, pressure, and ischemic). Participants included a total of 142 healthy subjects (76 men/66 women), 119 non-Hispanic whites and 23 African Americans. Three sessions of pain testing were completed prior to and following an intravenous administration of morphine (0.08 mg/kg), butorphanol (0.016 mg/kg), and placebo (saline) in counterbalanced order. A change score was calculated from the difference between the pre-drug and postdrug values. Three separate change scores (morphine, saline, and butorphanol) were computed for each experimental pain variable. Mixed-model analyses of covariance were performed on analgesic change scores. Significant sex differences emerged for predrug pain measures with minimal differences for race. Sex differences in opioid analgesia were not demonstrated. However, significant race differences and race X drug interactions emerged for thermal, pressure, and ischemic pain measures. The pattern of results generally indicated that for pressure and ischemic pain, African American subjects showed greater analgesic responses to both medications compared with non-Hispanic whites. For thermal pain threshold, butorphanol but not morphine analgesia was greater for African American vs non-Hispanic whites. Findings are among the first to demonstrate race differences in a laboratory study of opioid analgesia. Wiley Periodicals, Inc.

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

    PubMed Central

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

    2016-01-01

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

  1. Regional brain signal variability: a novel indicator of pain sensitivity and coping.

    PubMed

    Rogachov, Anton; Cheng, Joshua C; Erpelding, Nathalie; Hemington, Kasey S; Crawley, Adrian P; Davis, Karen D

    2016-11-01

    Variability in blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals reflects the moment-by-moment fluctuations in resting-state fMRI (rs-fMRI) activity within specific areas of the brain. Regional BOLD signal variability was recently proposed to serve an important functional role in the efficacy of neural systems because of its relationship to behavioural performance in aging and cognition studies. We previously showed that individuals who better cope with pain have greater fluctuations in interregional functional connectivity, but it is not known whether regional brain signal variability is a mechanism underlying pain coping. We tested the hypothesis that individual pain sensitivity and coping is reflected by regional fMRI BOLD signal variability within dynamic pain connectome-brain systems implicated in the pain experience. We acquired resting-state fMRI and assessed pain threshold, suprathreshold temporal summation of pain, and the impact of pain on cognition in 80 healthy right-handed individuals. We found that regional BOLD signal variability: (1) inversely correlated with an individual's temporal summation of pain within the ascending nociceptive pathway (primary and secondary somatosensory cortex), default mode network, and salience network; (2) was correlated with an individual's ability to cope with pain during a cognitive interference task within the periaqueductal gray, a key opiate-rich brainstem structure for descending pain modulation; and (3) provided information not captured from interregional functional connectivity. Therefore, regional BOLD variability represents a pain metric with potential implications for prediction of chronic pain resilience vs vulnerability.

  2. [Measurement of postoperative pain: analysis of the sensitivity of various self-evaluation instruments].

    PubMed

    Lázaro, C; Caseras, X; Torrubia, R; Baños, J E

    2003-05-01

    This study compared the sensitivity of two one-dimensional scales (a visual analog scale [VAS] and a verbal scale of pain intensity [VSPI]) and one multidimensional scale (McGill Pain Questionnaire-Spanish Version [MPQ-SV]) for detecting changes in pain after a variety of surgical procedures with postoperative analgesia provided by one of two methods. Forty-two patients who underwent abdominal surgery, hysterectomy, cesarean, inguinal herniorrhaphy, subcostal or medial laparoscopic cholecystectomy were studied. Postoperative analgesia consisted of 1 mg/Kg of intravenous pethidine every 4 h in group one (n = 20) and intramuscular diclofenac every 12 h in group two. Assessment was at 24 h and/or at 48 and 72 h using the VAS, the VSPI and the MPQ-SV. All the scales were useful for assessing postoperative pain, giving estimates that were sensitive to variations in pain on days after the operation. The MPQ-SV was able to detect different pain-producing capacities for the surgical procedures more effectively than were the one-dimensional scales. The MPQ-SV was also able to discriminate the qualitative and quantitative differences among the mechanisms of action of opioid and nonsteroidal anti-inflammatory drugs, whereas the one-dimensional scales were unable to distinguish therapeutic approach. All the scales were sensitive to changes in postoperative pain, but the MPQ-SV gave more precise information of differences between analgesic treatments and among operations.

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

    PubMed

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

    2011-12-01

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

  4. Pain-sensitive temperament: does it predict procedural distress and response to psychological treatment among children with cancer?

    PubMed

    Chen, E; Craske, M G; Katz, E R; Schwartz, E; Zeltzer, L K

    2000-06-01

    To evaluate the relationship between pain sensitivity and children's distress during lumbar punctures (LPs), and whether pain sensitivity functions as a moderator of children's responses to a psychological intervention aimed at reducing LP distress. Fifty-five children with acute lymphoblastic leukemia (ages 3 to 18) and their parents completed a questionnaire measure of pain sensitivity. Self-report, physiological, and observed measures of distress were collected during the study baseline LP. Children were then randomized into a psychological intervention or an attention control group. Postintervention and follow-up LPs were observed. Higher levels of pain sensitivity were associated with greater anxiety and pain, both prior to and during the LP. Preliminary analyses indicated that pain sensitivity moderated the effects of intervention on distress. Children who were more pain-sensitive and who received no intervention showed greater increases in LP distress over time. In contrast, children who were more pain-sensitive and who received intervention showed greater decreases in LP distress over time. A measurement of pain sensitivity may be useful in pediatric oncology settings for effectively targeting pain-vulnerable children for psychological intervention. Preliminary analyses indicate that an empirically-supported intervention for procedural distress is efficacious for those children who are most pain-sensitive.

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

    PubMed

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

    2017-05-25

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

  6. 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.

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

    PubMed

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

    2012-03-01

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

  8. Nociceptor Sensitization Depends on Age and Pain Chronicity(1,2,3).

    PubMed

    Weyer, Andy D; Zappia, Katherine J; Garrison, Sheldon R; O'Hara, Crystal L; Dodge, Amanda K; Stucky, Cheryl L

    2016-01-01

    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.

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

    PubMed

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

    2010-06-01

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

  10. Topographical pressure and thermal pain sensitivity mapping in patients with unilateral lateral epicondylalgia.

    PubMed

    Ruiz-Ruiz, Beatriz; Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Arendt-Nielsen, Lars; Madeleine, Pascal

    2011-10-01

    Our aim was to quantify spatial differences in pressure and thermal pain sensitivity maps between patients with unilateral lateral epicondylalgia (LE) and age- and sex-matched controls. Pressure (PPT), cold (CPT), and heat (HPT) pain thresholds were assessed over 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) bilaterally in 16 subjects with strictly unilateral LE and 16 age- and sex-matched controls in a blinded design. Topographical pain sensitivity maps to pressure and thermal stimulation over the elbow in patients with LE and healthy controls were calculated. A multilevel 3-way ANCOVA test was applied to detect differences in topographical maps between groups. Subjects with LE showed bilateral lower PPT, higher CPT (pain at higher temperature) and lower HPT (pain at lower temperature) at all the measurement points as compared to controls (all, P < .01). PPT were lower at points over the extensor carpi radialis brevis (ECRB) muscle as compared to points over the extensor digitorum communis muscle (P < .01) and over the extensor carpi ulnaris muscle (P < .001). CPT and HPT were not significantly different between points (P > .05). Topographical pressure and thermal pain sensitivity maps revealed bilateral hyperalgesia in patients with strictly unilateral LE. LE patients exhibited heterogeneously distributed pressure pain hyperalgesia while cold or heat maps were homogenous. The most sensitive localizations for PPT assessment corresponded to the muscle belly of the ECRB. Our results confirm the role of ECRB muscle in LE and argue for evidence of peripheral and central sensitization mechanisms in patients with strictly unilateral symptoms. Topographical pressure and thermal sensitivity maps revealed bilateral hyperalgesia in patients with strictly unilateral lateral epicondylalgia (LE). LE patients exhibited heterogeneously distributed pressure pain hyperalgesia

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

    PubMed Central

    Mogil, Jeffrey S.

    1999-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with NSAIDs. The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain while a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present studies, palpation of the ipsilateral hindlimb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced FOS expression in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways by microinjection of lidocaine within the rostral ventromedial medulla (RVM) induced conditioned place preference (CPP) selectively in rats treated with the high dose of MIA. CPP to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, i.p. at −30 min). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that may guide drug discovery for treatment of advanced OA pain without the need for joint replacement. PMID:26694132

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

    Chronic pain is a major characteristic feature of sickle cell disease (SCD). The refractory nature of pain and the development of chronic pain syndromes in many patients with SCD suggest that central neural mechanisms contribute to pain in this disease. We used HbSS-BERK sickle mice, which show chronic features of pain similar to those observed in SCD, and determined whether sensitization of nociceptive neurons in the spinal cord contributes to pain and hyperalgesia in SCD. Electrophysiological recordings of action potential activity were obtained from single, identified dorsal horn neurons of the spinal cord in anesthetized mice. Compared to control HbAA-BERK mice, nociceptive dorsal horn neurons in sickle mice exhibited enhanced excitability as evidenced by enlarged receptive fields, increased rate of spontaneous activity, lower mechanical thresholds, enhanced responses to mechanical stimuli, and prolonged after-discharges following mechanical stimulation. These changes were accompanied by increased phosphorylation of mitogen activated protein kinases (MAPKs) in the spinal cord that are known to contribute to neuronal hyperexcitability, including c-Jun N-terminal kinase (JNK), p44/p42 extracellular signaling-regulated kinase (ERK), and p38. These findings demonstrate that central sensitization contributes to pain in SCD. PMID:25630029

  16. Role of induced negative and positive emotions in sensitivity to itch and pain in women.

    PubMed

    van Laarhoven, A I M; Walker, A L; Wilder-Smith, O H; Kroeze, S; van Riel, P L C M; van de Kerkhof, P C M; Kraaimaat, F W; Evers, A W M

    2012-08-01

    Itch and pain are common symptoms in skin disease. It has been suggested that negative emotions may play a role in itch and pain. To date, however, the role of emotions has only been studied for pain in experimental studies, not yet for itch. To investigate the effects of negative and positive emotions on the sensitivity to itch and pain. Film fragments were used to induce a negative or positive emotional state in healthy women. Itch and pain were induced using the following somatosensory stimuli: electrical stimulation, histamine iontophoresis and the cold pressor test. Results showed that the scores for itch and pain evoked by histamine and the cold pressor test, respectively, were significantly higher in the negative than in the positive emotion condition, whereas tolerance thresholds to electrical stimulation and the cold pressor test, and stimulus unpleasantness scores did not differ between the two conditions. These findings for the first time indicate in an experimental design that emotions play a role in sensitivity to somatosensory sensations of both itch and pain. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

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

    PubMed Central

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

    2015-01-01

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

  18. 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.

  19. [Influence of simulated microgravity on the threshold of pain sensitivity in humans with single dose of ketorolac].

    PubMed

    Baranov, M V; Kovalev, A S; Perfilov, D F; Chernogorov, R V; Repenkova, L G

    2015-01-01

    The data supporting the influence of simulated microgravity effects on pain sensitivity were obtained in the series of experiments involving human. In conditions of antiorthostatic hypokinesia (ANOH) and immersion revealed no reduction in pain sensitivity in the morning, which is typical for normal conditions. Ketorolac has no effect on pain sensitivity, when determining the pain threshold (PT) by method of thermoalgometry. However, the conditions of simulated microgravity substantially alter the pharmacokinetics of ketorolac, increasing the rate of absorption of the drug and reduce its relative bioavailability and retention time in the blood plasma. This may require changes in pain therapy schemes in space flight.

  20. 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.

  1. 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.

  2. 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.

  3. Different effects of physical exercise on cold pain sensitivity in fighter pilots with and without the history of acute in-flight neck pain attacks.

    PubMed

    Kemppainen, P; Hämäläinen, O; Könönen, M

    1998-04-01

    The cold pain sensitivity in fighter pilots was studied by using a cold pressor test. The pilots were divided into two groups: one group consisting of eight pilots (N = 8) who had experienced several acute in-flight neck pain attacks, and the control group (N = 8) who had not experienced these pain conditions under similar work and environment conditions. In each pilot cold pain thresholds and pain and unpleasantness responses to suprathreshold cold stimulations were recorded during repeated tests. The ratings of pain and unpleasantness responses to cold stimulations were evaluated by visual analog scales (VAS). The effect of exercise on cold pain sensitivity was tested in a separate experiment. Exercise was performed on a cycle ergometer at different workload levels (50-200 W). In the control conditions (resting measures) of this study during repeated cold pressor tests, the average pain thresholds and pain or unpleasantness responses to suprathreshold cold stimulation were not different between groups. Physical exercise increased pain thresholds (P < 0.001) in pilots with a history of neck pain attacks but not in control group. Exercise induced a significant decrease in pain responses and unpleasantness responses to suprathreshold stimulation in both groups. This exercise effect was more marked both in pain intensity (P < 0.05) and unpleasantness responses (P < 0.01) in pilots with a history of neck pain attacks. Moreover, exercise more markedly (P < 0.05) decreased unpleasantness than pain intensity responses in both groups of pilots. The results suggest that exercise stress-related analgesia mechanisms may be enhanced in pilots with a history of acute in-flight neck pain attacks. Moreover, sensory and nonsensory aspects of pain experience may be differentially influenced by exercise stress.

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

    PubMed

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

    2016-02-01

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

  5. Emotion induction moderates effects of anger management style on acute pain sensitivity.

    PubMed

    Burns, John W; Kubilus, Amanda; Bruehl, Stephen

    2003-11-01

    Anger management style (AMS) is related to both acute and chronic pain intensity. Recent work suggests that an anger expressive AMS in particular may influence acute pain, and that this effect may be most pronounced during anger provocation. The present study examined whether AMS was related to subsequent pain sensitivity without regard to prior emotion induction, only when a strong negative emotion was evoked, or only when anger was provoked. Sixty-four healthy normals partook in semi-structured interviews in which they recalled and verbally described an event in which either anger, sadness, or joy was elicited. They then underwent a cold pressor pain task. Results of hierarchical multiple regressions showed that an anger expressive AMS was related positively to pain threshold only for participants in the anger-recall condition, and that this effect was largely accounted for by their low SBP reactivity during emotion induction. An anger suppressive AMS was related positively to increases in self-reported pain severity, irrespective of emotion-induction condition, and this effect was not accounted for by reactivity in any cardiovascular index. Results extend those of previous studies by illuminating the potential importance of behavioral anger expression for individuals prone to express anger in modulating their reactivity and pain sensitivity. Findings suggest that the detrimental effects of an anger expressive style on pain sensitivity may be ameliorated under conditions in which behavioral anger expression occurs. Results are discussed in terms of recent work suggesting that an expressive AMS is associated with endogenous opioid dysfunction in the absence of behavioral anger expression.

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

    PubMed

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

    2011-03-01

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

  7. Pain-related anxiety and anxiety sensitivity across anxiety and depressive disorders.

    PubMed

    Carleton, R Nicholas; Abrams, Murray P; Asmundson, Gordon J G; Antony, Martin M; McCabe, Randi E

    2009-08-01

    Fear-anxiety-avoidance models posit pain-related anxiety and anxiety sensitivity as important contributing variables in the development and maintenance of chronic musculoskeletal pain [Asmundson, G. J. G, Vlaeyen, J. W. S., & Crombez, G. (Eds.). (2004). Understanding and treating fear of pain. New York: Oxford University Press]. Emerging evidence also suggests that pain-related anxiety may be a diathesis for many other emotional disorders [Asmundson, G. J. G., & Carleton, R. N. (2005). Fear of pain is elevated in adults with co-occurring trauma-related stress and social anxiety symptoms. Cognitive Behaviour Therapy, 34, 248-255; Asmundson, G. J. G., & Carleton, R. N. (2008). Fear of pain. In: M. M. Antony & M. B. Stein (Eds.), Handbook of anxiety and the anxiety disorders (pp. 551-561). New York: Oxford University Press] and appears to share several elements in common with other fears (e.g., anxiety sensitivity, illness/injury sensitivity, fear of negative evaluation) as described by Reiss [Reiss, S. (1991). Expectancy model of fear, anxiety, and panic. Clinical Psychology Review, 11, 141-153] and Taylor [Taylor, S. (1993). The structure of fundamental fears. Journal of Behavior Therapy and Experimental Psychiatry, 24, 289-299]. The purpose of the present investigation was to assess self-reported levels of pain-related anxiety [Pain Anxiety Symptoms Scale-Short Form; PASS-20; McCracken, L. M., & Dhingra, L. (2002). A short version of the Pain Anxiety Symptoms Scale (PASS-20): preliminary development and validity. Pain Research and Management, 7, 45-50] across several anxiety and depressive disorders and to compare those levels to non-clinical and chronic pain samples. Participants consisted of a clinical sample (n=418; 63% women) with principal diagnoses of a depressive disorder (DD; n=22), panic disorder (PD; n=114), social anxiety disorder (SAD; n=136), obsessive-compulsive disorder (OCD; n=86), generalized anxiety disorder (GAD; n=46), or specific phobia (n=14

  8. Pain sensitivity and pericranial tenderness in children with tension-type headache: a controlled study

    PubMed Central

    Soee, Ann-Britt L; Skov, Liselotte; Kreiner, Svend; Tornoe, Birte; Thomsen, Lise L

    2013-01-01

    Purpose To compare tenderness and pain sensitivity in children (aged 7–17 years) with tension-type headache (TTH) and healthy controls using total tenderness score (TTS), pressure pain threshold (PPT), and pain perceived at suprapressure pain threshold (supraPPT). Patients and methods Twenty-three children with frequent episodic TTH, 36 with chronic TTH, and 57 healthy controls were included. TTS was measured bilaterally at seven pericranial myofascial structures. PPT and supraPPT were assessed in the finger, m. temporalis, and m. trapezius by a Somedic® algometer. SupraPPT was defined as the pain perceived at a stimulus calculated as the individual site-specific PPT + 50%. Statistics The effect of group, sex, age, headache frequency, intensity, and years on TTS, PPT, and supraPPT was analyzed by general linear models. Confirmatory factor analysis was analyzed for mutual relations between measurements. Results and conclusion Tenderness increased uniformly in both frequent episodic TTH (median 14; interquartile range [IQR] 10–18; P < 0.001) and chronic TTH (median 13; IQR 9–20; P < 0.001) compared to controls (median 5, IQR 3–11). However, the children with frequent episodic TTH and chronic TTH did not show significantly increased sensitivity when measured by PPT or supraPPT. Factor analysis confirmed that the site-specific measurements depended on general latent variables. Consequently, the PPT and supraPPT tests can be assumed to measure central pain-processing levels. PMID:23785242

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

    PubMed Central

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

    2012-01-01

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

  10. A rapamycin-sensitive signaling pathway is essential for the full expression of persistent pain states

    PubMed Central

    Géranton, Sandrine M.; Jiménez-Díaz, Lydia; Torsney, Carole; Tochiki, Keri K.; Stuart, Sarah A.; Leith, J. Lianne; Lumb, Bridget M.; Hunt, Stephen P.

    2010-01-01

    Translational control through the mammalian target of rapamycin (mTOR) is critical for synaptic plasticity, cell growth and axon guidance. Recently, it was also shown that mTOR signaling was essential for the maintenance of the sensitivity of subsets of adult sensory neurons. Here, we show that persistent pain states, but not acute pain behaviour, are substantially alleviated by centrally administered rapamycin, an inhibitor of the mTOR pathway. We demonstrate that rapamycin modulates nociception by acting on subsets of primary afferents and superficial dorsal horn neurons to reduce both primary afferent sensitivity and central plasticity. We found that the active form of mTOR is present in a subpopulation of myelinated dorsal root axons, but rarely in unmyelinated C- fibers, and heavily expressed in the dorsal horn by lamina I/III projection neurons that are known to mediate the induction and maintenance of pain states. Intrathecal injections of rapamycin inhibited the activation of downstream targets of mTOR in dorsal horn and dorsal roots and reduced the thermal sensitivity of A- fibers. Moreover, in vitro studies showed that rapamycin increased the electrical activation threshold of Aδ- fibers in dorsal roots. Taken together our results imply that central rapamycin reduces neuropathic pain by acting both on an mTOR positive subset of A- nociceptors and lamina I projection neurons and suggest a new pharmacological route for therapeutic intervention in persistent pain states. PMID:19940197

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

    PubMed

    Sayar, Gulsilay

    2017-01-01

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

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

    PubMed

    White, Hillary D; Robinson, Thomas D

    2015-08-01

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

  13. Sensitization to Acute Procedural Pain in Pediatric Sickle Cell Disease: Modulation by Painful Vaso-occlusive Episodes, Age, and Endothelin-1

    PubMed Central

    Schlenz, Alyssa M.; McClellan, Catherine B.; Mark, Teresa R.M.; McKelvy, Alvin D.; Puffer, Eve; Roberts, Carla W.; Sweitzer, Sarah M.; Schatz, Jeffrey C.

    2012-01-01

    The impact of pain early in life is a salient issue for sickle cell disease (SCD), a genetic condition characterized by painful vaso-occlusive episodes (VOEs) that can begin in the first year of life and persist into adulthood. This study examined the effects of age and pain history (age of onset and frequency of recent VOEs) on acute procedural pain in children with SCD. Endothelin-1, a vaso-active peptide released during VOEs and acute tissue injury, and its precursor, Big Endothelin, were explored as markers of pain sensitization and vaso-occlusion. Sixty-one children with SCD (ages 2 to 18) underwent venipuncture at routine health visits. Procedural pain was assessed via child- and caregiver-reports and observational distress. Pain history was assessed using retrospective chart review. Three primary results were found: 1) younger age was associated with greater procedural pain across pain outcomes, 2) higher frequency of VOEs was associated with greater procedural pain based on observational distress (regardless of age), and 3) age was found to moderate the relationship between VOEs and procedural pain for child-reported pain and observational distress for children five years of age and older. Associations between the endothelin variables and pain prior to venipuncture were also observed. PMID:22633685

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

    PubMed

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

    2013-05-01

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

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

    PubMed

    Jarolim, Petr

    2015-04-01

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

  16. 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

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

    PubMed

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

    2017-10-15

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

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

    Musculoskeletal pain and stress-related disorders are leading causes of impaired work ability, sickness absences and disability pensions. However, knowledge about the combined detrimental effect of pain and stress on work ability is lacking. This study investigates the association between pain in the neck-shoulders, perceived stress, and work ability. In a cross-sectional survey at a large pharmaceutical company in Denmark 473 female laboratory technicians replied to questions about stress (Perceived Stress Scale), musculoskeletal pain intensity (scale 0–10) of the neck and shoulders, and work ability (Work Ability Index). General linear models tested the association between variables. In the multi-adjusted model, stress (p < 0.001) and pain (p < 0.001) had independent main effects on the work ability index score, and there was no significant stress by pain interaction (p = 0.32). Work ability decreased gradually with both increased stress and pain. Workers with low stress and low pain had the highest Work Ability Index score (44.6 (95% CI 43.9–45.3)) and workers with high stress and high pain had the lowest score (32.7 (95% CI 30.6–34.9)). This cross-sectional study indicates that increased stress and musculoskeletal pain are independently associated with lower work ability in female laboratory technicians. PMID:26690466

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

    PubMed

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

    2015-12-11

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

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

    PubMed Central

    Riquelme, Inmaculada; Hatem, Samar M.

    2016-01-01

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

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

    PubMed

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

    2003-12-01

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

  3. 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.

  4. Forebrain-mediated sensitization of central pain pathways: 'non-specific' pain and a new image for MT.

    PubMed

    Zusman, M

    2002-05-01

    Manual therapy (MT-) is moving beyond its empirical origins and into an era of evidence-based practice. Mechanisms for the appearance of clinically observed symptoms and signs are beng incorporated into its clinical reasoning process. The recent, but well-documented phenomenon, central sensitization, is recognized as being one such mechanism. Anatomical, physiological, behavioural and clinical evidence demonstrate that, in addition to input from the periphery, central sensitization can be enhanced or maintained by supraspinal processes involving cognitions, attention ('focussing') and emotions. These forebrain products may, therefore, make a significant contribution to the symptoms and signs of common musculoskeletal presentations such as 'non-specific' back pain and fibromyalgia. The evidence can also be interpreted to provide MT with an acceptable role in the management of these patients.

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

    PubMed Central

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

    2016-01-01

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

  6. The comparative effects of spinal and peripheral thrust manipulation and exercise on pain sensitivity and the relation to clinical outcome: a mechanistic trial using a shoulder pain model.

    PubMed

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

    2015-04-01

    Single-blind randomized trial. To compare the effects of cervical and shoulder thrust manipulation (TM) and exercise on pain sensitivity, and to explore associations with clinical outcomes in patients with shoulder pain. Experimental studies indicate that spinal TM has an influence on central pain processes, supporting its application for treatment of extremity conditions. Direct comparison of spinal and peripheral TM on pain sensitivity has not been widely examined. Seventy-eight participants with shoulder pain (36 female; mean ± SD age, 39.0 ± 14.5 years) were randomized to receive 3 treatments of cervical TM (n = 26), shoulder TM (n = 27), or shoulder exercise (n = 25) over 2 weeks. Twenty-five healthy participants (13 female; mean ± SD age, 35.2 ± 11.1 years) were assessed to compare pain sensitivity with that in clinical participants at baseline. Primary outcomes were changes in local (eg, shoulder) and remote (eg, tibialis anterior) pressure pain threshold and heat pain threshold occurring over 2 weeks. Secondary outcomes were shoulder pain intensity and patient-rated function at 4, 8, and 12 weeks. Analysis-of-variance models and partial-correlation analyses were conducted to examine comparative effects and the relationship between measures. At baseline, clinical participants demonstrated lower local (mean difference, - 1.63 kg; 95% confidence interval [CI]: -2.40, -0.86) and remote pressure pain threshold (mean difference, -1.96 kg; 95% CI: -3.09, -0.82) and heat pain threshold (mean difference, -1.15°C; 95% CI: -2.06, -0.24) compared to controls, suggesting enhanced pain sensitivity. Following intervention, there were no between-group differences in pain sensitivity or clinical outcome (P>.05). However, improvements were noted, regardless of intervention, for pressure pain threshold (range of mean differences, 0.22-0.32 kg; 95% CI: 0.03, 0.43), heat pain threshold (range of mean differences, 0.30-0.58; 95% CI: 0.06, 0.96), pain intensity (range of

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

    PubMed

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

    2012-06-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-02-19

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

  13. Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity

    PubMed Central

    Sorge, Robert E; Trang, Tuan; Dorfman, Ruslan; Smith, Shad B; Beggs, Simon; Ritchie, Jennifer; Austin, Jean-Sebastien; Zaykin, Dmitri V; Meulen, Heather Vander; Costigan, Michael; Herbert, Teri A; Yarkoni-Abitbul, Merav; Tichauer, David; Livneh, Jessica; Gershon, Edith; Zheng, Ming; Tan, Keith; John, Sally L; Slade, Gary D; Jordan, Joanne; Woolf, Clifford J; Peltz, Gary; Maixner, William; Diatchenko, Luda; Seltzer, Ze'ev; Salter, Michael W; Mogil, Jeffrey S

    2012-01-01

    Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary1. Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da2,3. Using genome-wide linkage analyses, we discovered an association between nerve-injury–induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain. PMID:22447075

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

    PubMed Central

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

    2009-01-01

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

  15. Allergic sensitization to laboratory animals is more associated with asthma, rhinitis, and skin symptoms than sensitization to common allergens.

    PubMed

    Simoneti, C S; Ferraz, E; de Menezes, M B; Bagatin, E; Arruda, L K; Vianna, E O

    2017-08-08

    Workers exposed to laboratory animals have a high risk of developing laboratory animal allergy (LAA). Atopy seems to be the main risk factor for LAA. We hypothesized that occupational sensitization is a better predictor for the development of asthma, rhinitis, and bronchial hyperresponsiveness (BHR) than common sensitization. To investigate the association between occupational sensitization to laboratory animals and clinical outcomes. This was a cross-sectional study performed at two universities on students and employees dealing with small rodents. The subjects were allocated in groups: non-sensitized, common sensitization, or occupational sensitization, according to the results of the skin prick test (SPT). All subjects answered a questionnaire about animal exposures, symptoms, allergic diseases, and underwent spirometry and bronchial challenge test with mannitol. Multivariate analysis was performed using Poisson regression to estimate the prevalence ratio (PR). Data from 453 volunteers were analysed. Non-sensitized group comprised 237 subjects; common sensitization group, 142 subjects; and occupational sensitization group, 74 subjects. Occupational sensitization was associated with greater risk for all outcomes studied. When the common sensitization group was reference, skin symptoms had PR of 1.36, 95% confidence interval (CI): 1.01-1.85; wheezing had PR of 1.75, CI 95%: 1.21-2.53; rhinitis had PR of 1.25, 95%: 1.11-1.40; nocturnal dyspnoea had PR of 2.40, 95% CI: 1.31-4.40; bronchial hyperresponsiveness (BHR) had PR of 2.47, 95% CI: 1.50-4.09; and confirmed asthma had PR of 2.65, 95% CI: 1.45-4.85. In addition, the overlap of asthma, rhinitis, and skin symptoms in a same subject was significantly more prevalent in the occupational sensitization group, 16.2% versus 4.9% in the common sensitization group. Occupational sensitization is associated with allergic symptoms and respiratory diseases. SPT with occupational allergens along with other parameters may

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

    PubMed

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

    2017-04-01

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

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

    PubMed Central

    Carbone, Larry; Austin, Jamie

    2016-01-01

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

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

    PubMed

    Carbone, Larry; Austin, Jamie

    2016-01-01

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2014-11-07

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

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

    PubMed

    Carbone, Larry

    2012-05-01

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

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

    PubMed

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

    2012-03-01

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

  4. Effects of aerobic exercise on pain sensitivity, heart rate recovery, and health-related quality of life in patients with chronic musculoskeletal pain.

    PubMed

    Öte Karaca, Şeyda; Demirsoy, Nesrin; Günendi, Zafer

    2017-06-01

    We aimed to investigate the effects of aerobic exercise on pain perception, sensitivity, and health-related quality of life; to assess its effect on parasympathetic tonus by analysis of heart rate recovery; and to examine the effects of parasympathetic tone on pain sensitivity in patients with chronic musculoskeletal pain. Fifty patients with chronic musculoskeletal pain were randomized into two groups: control group (C group) and aerobic exercise group (AE group). Both groups received conventional physical therapy for 2 weeks; the AE group performed submaximal aerobic exercise on a treadmill for 30 min additionally. Exercise test, pressure-pain threshold measurement, short form-36, and visual analog scale were administered initially and finally for evaluation. Visual analog scale scores in both groups decreased significantly after treatment (P<0.001). Pressure-pain threshold sum increased significantly in the AE group, remaining unchanged in the C group. Increase in exercise test duration was significant in the AE group compared with the C group (P=0.0002). Heart rate recovery did not change with therapy in the groups. For short form-36, the AE group showed alterations in role limitations because of physical problems and general health perceptions; both groups showed a significant improvement in the physical function and bodily pain subscales, but mental health significantly improved only in C group. Short-term aerobic exercise along with conventional physical therapy decreased pain sensitivity and increased aerobic capacity, with significant improvements in health-related quality of life.

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

    Sutton, Blair C.; Opp, Mark R.

    2014-01-01

    Study Objectives: Musculoskeletal pain in humans is often associated with poor sleep quality. We used a model in which mechanical hypersensitivity was induced by injection of acidified saline into muscle to study the impact of musculoskeletal sensitization on sleep of mice. Design: A one month pre-clinical study was designed to determine the impact of musculoskeletal sensitization on sleep of C57BL/6J mice. Methods: We instrumented mice with telemeters to record the electroencephalogram (EEG) and body temperature. We used an established model of musculoskeletal sensitization in which mechanical hypersensitivity was induced using two unilateral injections of acidified saline (pH 4.0). The injections were given into the gastrocnemius muscle and spaced five days apart. EEG and body temperature recordings started prior to injections (baseline) and continued for three weeks after musculoskeletal sensitization was induced by the second injection. Mechanical hypersensitivity was assessed using von Frey filaments at baseline (before any injections) and on days 1, 3, 7, 14, and 21 after the second injection. Results: Mice injected with acidified saline developed bilateral mechanical hypersensitivity at the hind paws as measured by von Frey testing and as compared to control mice and baseline data. Sleep during the light period was fragmented in experimental mice injected with acidified saline, and EEG spectra altered. Musculoskeletal sensitization did not alter the duration of time spent in wakefulness, non-rapid eye movement sleep, or rapid eye movement sleep. Conclusions: Musculoskeletal sensitization in this model results in a distinct sleep phenotype in which sleep is fragmented during the light period, but the overall duration of sleep is not changed. This study suggests the consequences of musculoskeletal pain include sleep disruption, an observation that has been made in the clinical literature but has yet to be studied using preclinical models. Citation: Sutton BC

  7. Temporomandibular disorder and optimism: relationships to ischemic pain sensitivity and interleukin-6.

    PubMed

    Costello, Nancy L; Bragdon, Edith E; Light, Kathleen C; Sigurdsson, Asgeir; Bunting, Shelley; Grewen, Karen; Maixner, William

    2002-11-01

    The current study examined patients with temporomandibular disorders (TMD) (n=20) and pain-free controls (n=28) under stress and relaxation conditions. Interleukin-6 (IL-6), norepinephrine and epinephrine (NE and E) were measured both before and during each of two conditions: a non-stressful relaxation period and a speech stressor. Ischemic pain sensitivity was also assessed after each of these conditions. Optimism (Life Orientation Test (LOT)), which has been associated with better outcomes in relationship to health and disease, was also evaluated in relationship to ischemic pain tolerance and unpleasantness ratings as well as to IL-6 levels under the two conditions. Regression analysis determined the unique contribution of each predictor and the interaction between Optimism and Group (TMD versus controls) after controlling for gender and blood pressure. During stress, IL-6 levels appeared to parallel NE with only controls displaying significant increases. After controlling for depressed mood, TMD patients as a whole showed a significantly blunted response in IL-6 levels produced during stress as compared to controls (beta=0.31*). Although TMD subjects as a whole did not show the expected greater pain sensitivity to the ischemic task, those displaying a less optimistic style did exhibit lower pain tolerance times (beta=-0.61*) and higher pain unpleasantness ratings (beta=0.48*), compared with low optimism controls and high optimism TMD patients. Less optimistic TMD patients also had higher NE and IL-6 levels during stress than other TMD patients, while optimism was unrelated to responses in controls (*P<0.05).

  8. Women with Chronic and Episodic Migraine Exhibit Similar Widespread Pressure Pain Sensitivity.

    PubMed

    Palacios-Ceña, María; Lima Florencio, Lidiane; Natália Ferracini, Gabriela; Barón, Johanna; Guerrero, Ángel L; Ordás-Bandera, Carlos; Arendt-Nielsen, Lars; Fernández-de-Las-Peñas, César

    2016-11-01

    To investigate widespread pressure hyperalgesia in the trigemino-cervical and extra-trigeminal (distant pain-free) regions in women with episodic and chronic migraine. Fifty-one women with episodic migraine, 52 women with chronic migraine, and 52 healthy women without headache history were recruited. Pressure pain thresholds (PPT) were bilaterally assessed over the trigeminal area (i.e., temporalis muscle), cervical area (i.e., C5/C6 zygapophyseal joint), and two extra-trigeminal areas (i.e., second metacarpal, tibialis anterior muscle) in a blinded design. Clinical features of migraine and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were also assessed. The multivariate analysis of covariance (ANCOVA) revealed that PPTs were significantly decreased bilaterally over trigeminal and extra-trigeminal points in migraine patients compared to healthy women (all sites, P < 0.001). No differences between episodic and chronic migraine were observed (all, P > 0.919). The presence of neck pain (all, P > 0.282), anxiety (P > 0.425) or depression (all, P > 0.316) did not influence the results. The intensity of migraine pain was negatively associated with widespread pressure pain sensitivity: The greater the intensity of migraine attacks, the lower the widespread PPT levels, i.e., the greater the widespread sensitization. This study found similar widespread pressure hypersensitivity in women with episodic or chronic migraine suggesting that central manifestations are involved both in episodic and chronic migraine. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2009-06-01

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

  10. Pain sensitivity is normalized after a repeated bout of eccentric exercise.

    PubMed

    Hosseinzadeh, Mahdi; Andersen, Ole K; Arendt-Nielsen, Lars; Madeleine, Pascal

    2013-10-01

    The purpose of this study was to investigate the effect of repeated bouts of eccentric exercise on the nociceptive withdrawal reflex (NWR) threshold, a measure of sensitivity in the spinal nociceptive system. Sixteen healthy students (age 25.7 ± 0.6 years, BMI 24.8 ± 1 kg m(-2)) participated in this randomized, controlled, crossover study. Two identical bouts of high-intensity eccentric exercises were performed on the tibialis anterior muscle 7 days apart. Control sessions involving no exercise were performed 4 weeks apart the exercise sessions. Pressure pain thresholds (PPT) and the NWR threshold were recorded before, immediately after, and 1 day after both bouts of exercise. Pressure pain thresholds decreased significantly at two of the muscle belly sites on the day after initial bout compared with baseline. NWR threshold decreased by 25 ± 4 % immediately after initial bout and by 30 ± 5 % the next day (p < 0.05) as an indication of generalized pain hypersensitivity. On the contrary, no changes were found in both pain thresholds after second bout of eccentric exercise indicating that both localized and generalized pain sensitivity were normalized. In conclusion, this study for the first time documented that an initial bout of unaccustomed high-intensity eccentric exercise, which results in muscle soreness can induce central sensitization. A repeated bout of exercise, however, facilitates inherent protective spinal mechanisms against the development of muscle soreness.

  11. Monitoring Sensitive Bat Species at Los Alamos National Laboratory

    SciTech Connect

    Schoenberg, Kari M.

    2014-01-15

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

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

    PubMed Central

    Rossi, Heather L.; Neubert, John K.

    2008-01-01

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

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

    SciTech Connect

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

    1990-01-01

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

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

    PubMed Central

    2009-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2008-01-01

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

  17. Central pain sensitization, COMT Val158Met polymorphism, and emotional factors in fibromyalgia.

    PubMed

    Desmeules, Jules; Chabert, Jocelyne; Rebsamen, Michela; Rapiti, Elisabetta; Piguet, Valerie; Besson, Marie; Dayer, Pierre; Cedraschi, Christine

    2014-02-01

    Neurobiological evidence points to altered central nervous system processing of nociceptive stimuli in fibromyalgia. Enzymes like catechol-O-methyl-transferase (COMT) are involved in the elimination of catecholamines playing a possible role in central sensitization and pain. We used quantitative sensory testing to evidence central sensitization in fibromyalgia patients and test whether COMTVal158Met polymorphism, associated with a reduction in enzyme activity, plays a role in sensitized patients. Pain evaluation and quantitative sensory testing were performed including the spinal nociceptive flexion reflex, a physiologic correlate for the evaluation of central nociceptive pathways. Quality of life and distress questionnaires were used. A total of 137 fibromyalgia patients were assessed and compared to 99 matched controls. Central sensitization (nociceptive flexion reflex <27 mA) was present in 95/134 (71%) patients. Among them, COMT p.Val158Met polymorphism displayed a significant linear "genotype effect" (P = .033), with the Met/Met (mean = 17.8 ± 4.8 mA) and Val/Val (mean = 21.4 ± 4.6 mA) subgroups at the opposite ends of the nociceptive flexion reflex threshold (Met/Met vs Val/Val P = .015) and the Val/Met subgroup (mean = 19 ± 4.9 mA) in between (Val/Met vs Val/Val P = .041). Spontaneous moderate to severe pain was more likely to be associated with COMT Met/Met genotype. Patients showed important emotional distress compared to controls. In sensitized patients, the COMT Met/Met subgroup showed systematically-though not significantly-worse scores for all psychological variables. The association between COMT p.Val158Met polymorphism and central sensitization in fibromyalgia is essential as it refers to the severity of central sensitization and may be a risk factor for treatment outcome. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Estrous cycle influences excitatory amino acid transport and visceral pain sensitivity in the rat: effects of early-life stress.

    PubMed

    Moloney, Rachel D; Sajjad, Jahangir; Foley, Tara; Felice, Valeria D; Dinan, Timothy G; Cryan, John F; O'Mahony, Siobhain M

    2016-01-01

    Early-life stress (ELS) is a recognized risk factor for chronic pain disorders, and females appear to be more sensitive to the negative effects of stress. Moreover, estrous cycle-related fluctuations in estrogen levels have been linked with alternating pain sensitivity. Aberrant central circuitry involving both the anterior cingulate cortex (ACC) and the lumbosacral spinal cord has also been implicated in the modulation of visceral pain in clinical and preclinical studies. Here we further investigate changes in visceral pain sensitivity and central glutamatergic systems in rats with respect to estrous cycle and ELS. We investigated visceral sensitivity in adult female Sprague-Dawley rats, which had undergone maternal separation (MS) in early life or remained non-separated (NS), by performing colorectal distension (CRD). We also assessed excitatory amino acid uptake through excitatory amino acid transporters (EAATs) in the lumbosacral spinal cord and ACC. NS animals in proestrus and estrus exhibited reduced EAAT uptake and decreased threshold to CRD. Moreover, total pain behaviors were increased in these stages. MS rats exhibited lower pain thresholds and higher total pain behaviors to CRD across all stages of the estrous cycle. Interestingly, cortical EAAT function in MS rats was inhibited in the low estrogen state-an effect completely opposite to that seen in NS rats. This data confirms that estrous cycle and ELS are significant factors in visceral sensitivity and fluctuations in EAAT function may be a perpetuating factor mediating central sensitization.

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

    PubMed

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

    2009-10-01

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

  20. Estradiol Sensitizes the Transient Receptor Potential Vanilloid 1 Receptor in Pain Responses.

    PubMed

    Payrits, Maja; Sághy, Éva; Cseko, Kata; Pohóczky, Krisztina; Bölcskei, Kata; Ernszt, Dávid; Barabás, Klaudia; Szolcsányi, János; Ábrahám, István M; Helyes, Zsuzsanna; Szoke, Éva

    2017-10-01

    Sex differences exist in chronic pain pathologies, and gonadal estradiol (E2) alters the pain sensation. The nocisensor transient receptor potential vanilloid 1 (TRPV1) receptor plays a critical role in triggering pain. Here we examined the impact of E2 on the function of TRPV1 receptor in mice sensory neurons in vitro and in vivo. Both mechano- and thermonociceptive thresholds of the plantar surface of the paw of female mice were significantly lower in proestrus compared with the estrus phase. These thresholds were higher in ovariectomized (OVX) mice and significantly lower in sham-operated mice in proestrus compared with the sham-operated mice in estrus phase. This difference was absent in TRPV1 receptor-deficient mice. Furthermore, E2 potentiated the TRPV1 receptor activation-induced mechanical hyperalgesia in OVX mice. Long pretreatment (14 hours) with E2 induced a significant increase in TRPV1 receptor messenger RNA expression and abolished the capsaicin-induced TRPV1 receptor desensitization in primary sensory neurons. The short E2 incubation (10 minutes) also prevented the desensitization, which reverted after coadministration of E2 and the tropomyosin-related kinase A (TrkA) receptor inhibitor. Our study provides in vivo and in vitro evidence for E2-induced TRPV1 receptor upregulation and sensitization mediated by TrkAR via E2-induced genomic and nongenomic mechanisms. The sensitization and upregulation of TRPV1 receptor by E2 in sensory neurons may explain the greater pain sensitivity in female mice. Copyright © 2017 Endocrine Society.

  1. KIMS, CEDIA, and HS-CEDIA immunoassays are inadequately sensitive for detection of benzodiazepines in urine from patients treated for chronic pain.

    PubMed

    Darragh, Alicia; Snyder, Marion L; Ptolemy, Adam S; Melanson, Stacy

    2014-01-01

    Patients treated for chronic pain may frequently undergo urine drug testing to monitor medication compliance and detect undisclosed prescribed or illicit drug use. Due to the increasing use and abuse of benzodiazepines, this class of medications is often included in drug screening panels. However, immunoassay-based methods lack the requisite sensitivity for detecting benzodiazepine use in this population primarily due to their poor cross-reactivity with several major urinary benzodiazepine metabolites. A High Sensitivity Cloned Enzyme Donor Immunoassay (HS-CEDIA), in which beta-glucuronidase is added to the reagent, has been shown to perform better than traditional assays, but its performance in patients treated for chronic pain is not well characterized. To determine the diagnostic accuracy of HS-CEDIA, as compared to the Cloned Enzyme Donor Immunoassay (CEDIA) and Kinetic Interaction of Microparticles in Solution (KIMS) screening immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS), for monitoring benzodiazepine use in patients treated for chronic pain. A study of the diagnostic accuracy of urine benzodiazepine immunoassays. The study was conducted at an academic tertiary care hospital with a clinical laboratory that performs urine drug testing for monitoring medication compliance in pain management. A total of 299 urine specimens from patients treated for chronic pain were screened for the presence of benzodiazepines using the HS-CEDIA, CEDIA, and KIMS assays. The sensitivity and specificity of the screening assays were determined using the LC-MS/MS results as the reference method. Of the 299 urine specimens tested, 141 (47%) confirmed positive for one or more of the benzodiazepines/metabolites by LC-MS/MS. All 3 screens were 100% specific with no false-positive results. The CEDIA and KIMS sensitivities were 55% (78/141) and 47% (66/141), respectively. Despite the relatively higher sensitivity of the HS-CEDIA screening assay (78%; 110

  2. Inflammation-induced hyperalgesia: effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia.

    PubMed

    Wegner, Alexander; Elsenbruch, Sigrid; Maluck, Janina; Grigoleit, Jan-Sebastian; Engler, Harald; Jäger, Marcus; Spreitzer, Ingo; Schedlowski, Manfred; Benson, Sven

    2014-10-01

    Inflammation-induced pain amplification and hypersensitivity play a role in the pathophysiology of numerous clinical conditions. Experimental endotoxemia has recently been implemented as model to analyze immune-mediated processes in human pain. In this study, we aimed to analyze dose- and time-dependent effects of lipopolysaccharide (LPS) on clinically-relevant pain models for musculoskeletal and neuropathic pain as well as the interaction among LPS-induced changes in inflammatory markers, pain sensitivity and negative affect. In this randomized, double-blind, placebo-controlled study, healthy male subjects received an intravenous injection of either a moderate dose of LPS (0.8 ng/kg Escherichiacoli), low-dose LPS (0.4 ng/kg), or saline (placebo control group). Pressure pain thresholds (PPT), mechanical pain sensitivity (MPS), and cold pain sensitivity (CP) were assessed before and 1, 3, and 6h post injection to assess time-dependent LPS effects on pain sensitivity. Plasma cytokines (TNF-α, IL-6, IL-8, IL-10) and state anxiety were repeatedly measured before, and 1, 2, 3, 4, and 6h after injection of LPS or placebo. LPS administration induced a systemic immune activation, reflected by significant increases in cytokine levels, body temperature, and negative mood with pronounced effects to the higher LPS dose. Significant decreases of PPTs were observed only 3h after injection of the moderate dose of LPS (0.8 ng/kg). MPS and CP were not affected by LPS-induced immune activation. Correlation analyses revealed that decreased PPTs were associated with peak IL-6 increases and negative mood. Our results revealed widespread increases in musculoskeletal pain sensitivity in response to a moderate dose of LPS (0.8 ng/kg), which correlate both with changes in IL-6 and negative mood. These data extend and refine existing knowledge about immune mechanisms mediating hyperalgesia with implications for the pathophysiology of chronic pain and neuropsychiatric conditions. Copyright

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1975-11-01

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

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

    PubMed

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

    2007-07-01

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

  6. 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.

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

    PubMed

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

    2017-02-04

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

  8. 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.

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

    PubMed Central

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

    2016-01-01

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

  10. Confirming the species-sensitivity distribution concept for endosulfan using laboratory, mesocosm, and field data.

    PubMed

    Hose, G C; Van den Brink, P J

    2004-11-01

    In Australia, water-quality trigger values for toxicants are derived using protective concentration values based on species-sensitivity distribution (SSD) curves. SSD curves are generally derived from laboratory data with an emphasis on using local or site-specific data. In this study, Australian and non-Australian laboratory-species based SSD curves were compared and the concept of species protection confirmed by comparison of laboratory-based SSD curves with local mesocosm experiments and field monitoring data. Acute LC50 data for the organochlorine pesticide endosulfan were used for these comparisons; SSD curves were fitted using the Burr type III distribution. SSD curves indicated that the sensitivities of Australian fish and arthropods were not significantly different from those of corresponding non-Australian taxa. Arthropod taxa in the mesocosm were less sensitive than taxa in laboratory tests, which suggests that laboratory-generated single-species data may be used to predict concentrations protective of semifield (mesocosm) systems. SSDs based on laboratory data were also protective of field populations.

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

    PubMed Central

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

    2014-01-01

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

  12. Effect of a cooling gel on pain sensitivity and healing of hot-iron cattle brands.

    PubMed

    Tucker, C B; Mintline, E M; Banuelos, J; Walker, K A; Hoar, B; Drake, D; Weary, D M

    2014-12-01

    Hot-iron branding is painful for cattle, but little is known about how long this pain lasts or effective alleviation methods. Previous work with pigs indicated that cooling burns with a gel (active ingredient: tea tree oil) improved healing compared to untreated wounds. Steers (210±21 kg) were hot-iron branded and allocated to 1 of 3 treatments: control (n=24), 1 gel application immediately after branding (1X; n=12), or 2 gel applications, 1 immediately after branding and one 1 d later (2X; n=12). Pain sensitivity was assessed by applying a known and increasing force with a von Frey anesthesiometer in 5 locations (in the center, at the top of, and 5 and 10 cm above the brand and on the equivalent location on the nonbranded side of the body) until animals showed a behavioral response. Healing was measured with a 6-point scale (1=fresh brand and 6=no scabbing and fully repigmented). Both measures, along with weight gain and surface temperature of the wound, were recorded before and 1, 2, 3, 7, 14, 21, 28, 35, 56, and 70 d after branding. The gel cooled the brand, with the most obvious differences on the day it was applied (3.7 to 4.2°C cooler than control; day×gel interaction, P=0.004). All wounds were at least partially repigmented by 70 d, but only 46% of brands were fully healed at this time. The healing process was slowed when a gel was applied twice (e.g., at 21 d, healing score of 2.5±0.1 and 2.7±0.1 vs. 2.0±0.2 for control and 1X vs. 2X, respectively; P=0.001). Brands tended to remain painful throughout the 70 d (in the center of the brand; before vs. d 1-35, P≤0.001; d 56, P=0.058; and d 70, P=0.092). Overall, gel had little effect on pain sensitivity. Weight gain was reduced on d 1 after branding compared to all other time points (P<0.001) but was not affected by gel application (P=0.277). In conclusion, applying gel did not improve outcomes after branding. In addition, by 70 d after the procedure, hot-iron brands still tended to be more painful than

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

    PubMed Central

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

    2007-01-01

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

  14. Temperature can influence gastric accommodation and sensitivity in functional dyspepsia with epigastric pain syndrome.

    PubMed

    Wang, Rui-Feng; Wang, Zhi-Feng; Ke, Mei-Yun; Fang, Xiu-Cai; Sun, Xiao-Hong; Zhu, Li-Ming; Zhang, Jing

    2013-09-01

    Functional dyspepsia-epigastric pain syndrome (FD-EPS) is characterized pathophysiologically by visceral hypersensitivity, but the effect of the temperature stimulation on gastric function has been seldom studied. The purpose of this study was to investigate the effects of liquid nutrients at different temperatures on the gastric accommodation, sensitivity, and gastric-wall compliance of healthy subjects (HS) and FD-EPS patients. Ten FD-EPS patients (Roma III criteria) and ten HS were recruited into the study. Intragastric pressure (IGP) and gastric perfusion were measured and compared following the administration of liquid nutrients at 37 °C on day 1 and at 8 °C on day 2. Seven patients developed abdominal discomfort or abdominal pain after being given cold liquid nutrient. The administration of liquid nutrient at 8 °C resulted in an increase of IGP in HS (P=0.044), a significant decrease in gastric perfusion (P<0.0001), a marked increase in IGP (P=0.015), and a dramatic reduction in gastric wall compliance (P=0.012) in patients compared to the effects of liquid nutrient at 37 °C. In addition, IGP in patients was lower than that in HS at 37 °C liquid nutrient (P=0.036), and the gastric perfusion volume in patients at maximal satiety was also significantly reduced at 8 °C liquid nutrient compared with HS (P=0.017). Cold stimulation can increase the IGP in HS and FD-EPS patients, elevate the visceral sensitivity and reduce the gastric volume of FD-EPS patients. FD-EPS patients who are sensitive to cold may develop epigastric discomfort or pain.

  15. Opioid-mediated pain sensitivity in mice bred for high voluntary wheel running.

    PubMed

    Li, Guo; Rhodes, Justin S; Girard, Isabelle; Gammie, Stephen C; Garland, Theodore

    2004-12-15

    We tested the hypothesis that thermal tail-flick latency, a common measure of pain sensitivity in rodents, would be altered in lines of mice that had been selectively bred for high voluntary wheel-running behavior. Specifically, we predicted that the selected (High-Runner) lines would show decreased pain sensitivity relative to their control (C; randombred) lines, and would respond differently to drugs that block opioid receptors. We first compared tail-flick latency between High-Runner and C female mice during the day (no wheel access) and at night (with wheel access). Second, we compared effects of the opioid antagonist naloxone (10 mg/kg, i.p.) on tail-flick latency during the day (no wheel access). Third, we compared effects of naloxone (5 and 10 mg/kg, i.p.) and naltrexone, a longer-lasting opioid antagonist (0.1, 1, 5, 10, 50, and 100 mg/kg, i.p.), on voluntary wheel running. Tail-flick latencies were longer at night (when mice were active on wheels), but mice from High-Runner and C lines did not differ during the day or night. Administration of naloxone (10 mg/kg, i.p.) decreased tail-flick latency measured during the day, equally in High-Runner and C mice. Naloxone (5 and 10 mg/kg, i.p.) and high doses of naltrexone (50 and 100 mg/kg, i.p.) decreased wheel running equally in High-Runner and C mice. Further studies will be required to determine whether other types of pain sensitivity have also failed to evolve in association with increased voluntary wheel running.

  16. Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain

    PubMed Central

    Tougas, G; Spaziani, R; Hollerbach, S; Djuric, V; Pang, C; Upton, A; Fallen, E; Kamath, M

    2001-01-01

    BACKGROUND—Acid reflux can elicit non-cardiac chest pain (NCCP), possibly through altered visceral sensory or autonomic function. The interactions between symptoms, autonomic function, and acid exposure are poorly understood.
AIM—To examine autonomic function in NCCP patients during exposure to oesophageal acid infusion.
SUBJECTS AND METHODS—Autonomic activity was assessed using power spectral analysis of heart rate variability (PSHRV), before and during oesophageal acidification (0.1 N HCl), in 28 NCCP patients (40.5 (10) years; 13 females) and in 10 matched healthy controls. Measured PSHRV indices included high frequency (HF) (0.15-0.5 Hz) and low frequency (LF) (0.06-0.15 Hz) power to assess vagal and sympathetic activity, respectively.
RESULTS—A total of 19/28 patients had angina-like symptoms elicited by acid. There were no significant manometric changes observed in either acid sensitive or insensitive patients. Acid sensitive patients had a higher baseline heart rate (82.9 (3.1) v 66.7 (3.5) beats/min; p<0.005) and lower baseline vagal activity (HF normalised area: 31.1 (1.9)% v 38.9 (2.3)%; p< 0.03) than acid insensitive patients. During acid infusion, vagal cardiac outflow increased (p<0.03) in acid sensitive but not in acid insensitive patients.
CONCLUSIONS—Patients with angina-like pain during acid infusion have decreased resting vagal activity. The symptoms elicited by perception of acid are further associated with a simultaneous increase in vagal activity in keeping with a vagally mediated pseudoaffective response.


Keywords: reflux disease; non-cardiac chest pain; acid reflux; autonomic nervous system; vagal response; sympathetic activity; heart rate variability; power spectrum analysis PMID:11600476

  17. Validation of a Symptom Provocation Test for Laboratory Studies of Abdominal Pain and Discomfort in Children and Adolescents

    PubMed Central

    Walker, Lynn S.; Williams, Sara E.; Smith, Craig A.; Garber, Judy; Van Slyke, Deborah A.; Lipani, Tricia; Greene, John W.; Mertz, Howard; Naliboff, Bruce D.

    2011-01-01

    Objective Assessed the convergent and discriminant validity of a water load symptom provocation test (WL-SPT) in creating visceral sensations similar to the naturally occurring sensations experienced by children with functional abdominal pain. Methods Participants were pediatric patients with functional abdominal pain (N = 110) and healthy school children (N = 120) between the ages of 8 and 16 years. Pain patients completed questionnaires describing gastrointestinal (GI) and nongastrointestinal (non-GI) symptoms associated with their typical abdominal pain episodes. Weeks later, the WL-SPT was administered to pain patients and well children. Before and immediately following the WL-SPT, children rated their symptoms. Results The WL-SPT produced (a) significant increases in children’s GI symptoms that were reliably predicted by the children’s naturally occurring GI symptoms, and (b) significantly greater increases in GI symptoms in pain patients than in well children. Conclusions The WL-SPT produces clinically relevant symptoms for laboratory studies of children with functional abdominal pain. PMID:16861396

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2011-09-15

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

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

    PubMed

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

    2013-01-01

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

  1. Immunoassay-Based Drug Tests Are Inadequately Sensitive for Medication Compliance Monitoring in Patients Treated for Chronic Pain.

    PubMed

    Snyder, Marion L; Fantz, Corrine R; Melanson, Stacy

    2017-02-01

    Enzyme immunoassays (EIA) have notable limitations for monitoring therapeutic compliance in pain management. Chromatography coupled with mass spectrometry provides definitive results and superior sensitivity and specificity over traditional EIA testing. To analyze and compare the sensitivity of EIA results together with known prescriptions to liquid chromatography-tandem mass spectrometry (LC-MS/MS) for monitoring drug use (and abuse) in patients treated for chronic pain. A total of 530 urine samples from patients being treated for chronic pain were studied. Pain management clinic in the United States. The samples were tested for a profile of chronic pain medications and illicit drugs with commercially available EIA kits followed by analysis with Agilent LC-MS/MS system. The EIAs exhibited poor sensitivity and high rates of false negative results in the pain management setting. For example, 21% of EIA for opiates show false negative results. Mass spectrometry methods were more sensitive, detected a broader range of drugs and metabolites, and could detect non-prescribed drug use and simulations in compliance. Patients do not always accurately report drug use information, and some drugs do not have EIA methods available for comparative purposes. Mass spectrometry is a more robust and reliable method for detection of drugs used in the pain management setting. Due to the extent of undisclosed use and abuse of medications and illicit drugs, LC-MS/MS testing is necessary for adequate and accurate drug detection. In addition, LC-MS/MS methods are superior in terms of sensitivity and number of compounds that can be screened, making this a better method for use in pain management. Key words: Pain management, enzyme immunoassays, mass spectrometry, urine drug testing, prescription status, compliance.

  2. Effect of Individually Tailored Biopsychosocial Workplace Interventions on Chronic Musculoskeletal Pain and Stress Among Laboratory Technicians: Randomized Controlled Trial.

    PubMed

    Jay, Kenneth; Brandt, Mikkel; Hansen, Klaus; Sundstrup, Emil; Jakobsen, Markus D; Schraefel, M C; Sjogaard, Gisela; Andersen, Lars L

    2015-01-01

    Chronic musculoskeletal pain is prevalent among laboratory technicians and work-related stress may aggravate the problem. This study investigated the effect of a multifaceted worksite intervention on pain and stress among laboratory technicians with chronic musculoskeletal pain using individually tailored physical and cognitive elements. This trial uses a single-blind randomized controlled design with allocation concealment in a 2-armed parallel group format among laboratory technicians. The trial "Implementation of physical exercise at the Workplace (IRMA09)--Laboratory technicians" was registered at ClinicalTrials.gov prior to participant enrolment. The study was conducted at the head division of a large private pharmaceutical company's research and development department in Denmark. The study duration was March 2014 (baseline) to July 2014 (follow-up). Participants (n = 112) were allocated to receive either physical, cognitive, and mindfulness group-based training (PCMT group) or a reference group (REF) for 10 weeks at the worksite. PCMT consisted of 4 major elements: 1) resistance training individually tailored to the pain affected area, 2) motor control training, 3) mindfulness, and 4) cognitive and behavioral therapy/education. Participants of the REF group were encouraged to follow ongoing company health initiatives. The predefined primary outcome measure was pain intensity (VAS scale 0-10) in average of the regions: neck, shoulder, lower and upper back, elbow, and hand at 10 week follow-up. The secondary outcome measure was stress assessed by Cohen´s perceived stress questionnaire. In addition, an explorative dose-response analysis was performed on the adherence to PCMT with pain and stress, respectively, as outcome measures. A significant (P < 0.0001) treatment by time interaction in pain intensity was observed with a between-group difference at follow-up of -1.0 (95%CI: -1.4 to -0.6). No significant effect on stress was observed (treatment by time P = 0

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

    PubMed

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

    2016-10-01

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

  4. The lipid kinase PIP5K1C regulates pain signaling and sensitization

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    2013-01-01

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

  12. 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

  13. Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia.

    PubMed

    Montilla-García, Ángeles; Tejada, Miguel Á; Perazzoli, Gloria; Entrena, José M; Portillo-Salido, Enrique; Fernández-Segura, Eduardo; Cañizares, Francisco J; Cobos, Enrique J

    2017-10-01

    Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80 mg/kg) induced a better recovery of grip strength than acetaminophen (40-320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or celecoxib (40-160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Libbrecht, Kenneth G.; Black, Eric D.

    2015-05-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Ji, Guangchen; Horváth, Csilla; Neugebauer, Volker

    2009-04-28

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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

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

    PubMed

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

    2010-08-06

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

  20. Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl.

    PubMed

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

    2014-12-03

    The P2X7 receptor is a member of the P2X family of adenosine 5'-triphosphate-gated cation channels. Several recent studies have demonstrated that this receptor is involved in mechanisms related to pain and inflammation. However, unknown is whether polymorphisms of the P2RX7 gene that encodes the human P2X7 receptor influence pain sensitivity and analgesic effects of opioids. The P2RX7 gene is known to be highly polymorphic. Thus, the present study examined associations between fentanyl sensitivity and polymorphisms in the P2RX7 gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery. We first conducted linkage disequilibrium (LD) analyses for 55 reported single-nucleotide polymorphisms (SNPs) in the region within and around the P2RX7 gene using genomic samples from 100 patients. In our samples, 42 SNPs were polymorphic, and a total of five LD blocks with six Tag SNPs (rs2708092, rs1180012, rs1718125, rs208293, rs1718136, and rs7132846) were observed. Thus, we further analyzed associations between genotypes/haplotypes of these Tag SNPs and clinical data using a total of 355 samples. In the genotype-based association study, only the rs1718125 G>A SNP tended to be associated with higher pain scores on a visual analog scale 24 h after surgery (VAS24). The haplotype-based association study showed that subjects with homozygous haplotype No.3 (GTAAAC; estimated frequency: 15.0%) exhibited significantly higher cold pain sensitivity and lower analgesic effects of fentanyl for acute cold pain in the cold pressor test. Conversely, subjects who carried haplotype No.1 (ACGGAC; estimated frequency: 24.5%) tended to exhibit lower cold pain sensitivity and higher analgesic effects of fentanyl. Furthermore, subjects with homozygous haplotype No.2 (GCGGAC; estimated frequency: 22.9%) exhibited significantly lower VAS24 scores. Cold pain sensitivity and analgesic effects of fentanyl were related to the SNP and haplotypes of the P2RX7 gene. The patients with the

  1. Pain.

    PubMed

    Melzack, Ronald; Katz, Joel

    2013-01-01

    Pain has many valuable functions. It often signals injury or disease, generates a wide range of adaptive behaviors, and promotes healing through rest. Despite these beneficial aspects of pain, there are negative features that challenge our understanding of the puzzle of pain, including persistent phantom limb pain after amputation or total spinal cord transection. Pain is a personal, subjective experience influenced by cultural learning, the meaning of the situation, attention, and other psychological variables. Pain processes do not begin with the stimulation of receptors. Rather, injury or disease produces neural signals that enter an active nervous system that (in the adult organism) is the substrate of past experience, culture, and a host of other environmental and personal factors. These brain processes actively participate in the selection, abstraction, and synthesis of information from the total sensory input. Pain is not simply the end product of a linear sensory transmission system; it is a dynamic process that involves continuous interactions among complex ascending and descending systems. The neuromatrix theory guides us away from the Cartesian concept of pain as a sensation produced by injury, inflammation, or other tissue pathology and toward the concept of pain as a multidimensional experience produced by multiple influences. These influences range from the existing synaptic architecture of the neuromatrix-which is determined by genetic and sensory factors-to influences from within the body and from other areas in the brain. Genetic influences on synaptic architecture may determine-or predispose toward-the development of chronic pain syndromes. WIREs Cogn Sci 2013, 4:1-15. doi: 10.1002/wcs.1201 For further resources related to this article, please visit the WIREs website.

  2. Effect of caffeine on leg-muscle pain during intense cycling exercise: possible role of anxiety sensitivity.

    PubMed

    Gliottoni, Rachael C; Motl, Robert W

    2008-04-01

    This experiment examined the effect of a moderate dose of caffeine on perceptions of leg-muscle pain during a bout of high-intensity cycling exercise and the role of anxiety sensitivity in the hypoalgesic effect of caffeine on muscle pain during exercise. Sixteen college-age women ingested caffeine (5 mg/kg body weight) or a placebo and 1 hr later completed 30 min of cycling on an ergometer at 80% of peak aerobic capacity. The conditions were completed in a counterbalanced order, and perceptions of leg-muscle pain were recorded during the bouts of exercise. Caffeine resulted in a large reduction in leg-muscle pain-intensity ratings compared with placebo (d = -0.95), and the reduction in leg-muscle pain-intensity ratings was larger in those with lower anxiety-sensitivity scores than those with higher anxiety-sensitivity scores (d = -1.28 based on a difference in difference scores). The results support that caffeine ingestion has a large effect on reducing leg-muscle pain during high-intensity exercise, and the effect is moderated by anxiety sensitivity.

  3. Bilateral pressure pain hypersensitivity over the hand as potential sign of sensitization mechanisms in individuals with thumb carpometacarpal osteoarthritis.

    PubMed

    Chiarotto, Alessandro; Fernandez-de-Las-Peñas, Cesar; Castaldo, Matteo; Villafañe, Jorge Hugo

    2013-10-01

    To investigate whether bilateral deep tissue pressure hyperalgesia exists in individuals with unilateral thumb carpometacarpal osteoarthritis (CMC OA). A total of 32 patients with CMC OA (29 females and 3 males, aged 69-90 years old) and 32 healthy matched controls (29 females and 3 males, aged 70-90 years) were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over the first CMC joint, the hamate bone and the lateral epicondyle in a blinded design. Mixed models analyses of variance were conducted to determine the differences in pressure pain sensitivity between groups and sides. The results showed that PPTs were significantly decreased over the first CMC joint (F = 6.551, P = 0.012) and the hamate bone (F = 9.783, P = 0.002) but not over the lateral epicondyle (F = 2.712, P = 0.102) in patients with thumb CMC OA as compared with healthy controls; patients with unilateral thumb CMC OA exhibited bilateral pressure pain hyperalgesia in both hands compared with healthy people. PPTs were not significantly associated to the intensity of pain (all, P > 0.05). This study revealed bilateral localized pressure pain hypersensitivity over the hand in individuals with unilateral thumb CMC OA, suggesting spinal cord sensitization mechanisms in this population. Future studies should analyze the presence of widespread pressure pain sensitivity in patients with thumb CMC OA to further determine the presence of central sensitization mechanisms. Wiley Periodicals, Inc.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. 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

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

    PubMed

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

    2016-12-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2015-04-01

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

  10. Differential sensitivity of three experimental pain models in detecting the analgesic effects of transdermal fentanyl and buprenorphine.

    PubMed

    Koltzenburg, Martin; Pokorny, Rolf; Gasser, Urs E; Richarz, Ute

    2006-12-15

    This is the first randomized controlled trial that tests the analgesic efficacy of transdermally delivered opioids in healthy volunteers and that assesses the sensitivity of different experimental pain tests to detect analgesia in this setting. Transdermal application of the full agonist fentanyl (TDF: 12.5 or 25 microg/h) and the partial agonist buprenorphine (TDB: 35 microg/h) was compared in three experimental models of acute pain (heat pain, painful electrical stimulation, cold pressor) in a double-blind, randomized, placebo-controlled, 4-arm crossover study with 20 healthy subjects (15 men, 5 women). Patches were administered for 72 h and pain levels measured at baseline and 24 and 72 h, with an 11-day wash-out. The cold pressor test was most sensitive to analgesic effects, with significant reductions in area under the pain intensity curve for all active compounds at 24 h (average reductions: 14% TDF 12.5 microg/h, 35% TDF 25 microg/h, 43% TDB 35 microg/h). There were significant increases in heat pain threshold for TDF 25 microg/h and TDB 35 microg/h. Painful electrical stimulation failed to demonstrate an analgesic effect. The magnitude of analgesia in the cold pressor model showed some correlation with TDF dosage and comparable effects for the full agonist fentanyl and the partial agonist buprenorphine. We conclude that the cold pressor test was most sensitive to analgesic effects in healthy subjects and that a transdermal dose of 12.5 microg/h fentanyl achieved significant pain reduction compared with placebo. Subjects experienced opioid-typical AEs including dizziness, nausea and vomiting. No serious AEs occurred.

  11. Mechano-sensitive nociceptors are required to detect heat pain thresholds and cowhage itch in human skin.

    PubMed

    Weinkauf, B; Dusch, M; van der Ham, J; Benrath, J; Ringkamp, M; Schmelz, M; Rukwied, R

    2016-02-01

    Mechano-sensitive and mechano-insensitive C-nociceptors in human skin differ in receptive field sizes and electrical excitation thresholds, but their distinct functional roles are yet unclear. After blocking the lateral femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin(®) 1%), we mapped the skin innervation territory being anaesthetic to mechanical pin prick but sensitive to painful transcutaneous electrical stimuli. Such 'differentially anaesthetic zones' indicated that the functional innervation with mechano-sensitive nociceptors was absent but the innervation with mechano-insensitive nociceptors remained intact. In these areas, we explored heat pain thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon reflex flare. In differentially anaesthetic skin, heat pain thresholds were above the cut-off of 50°C (non-anaesthetized skin 47 ± 0.4°C). Pain ratings to 30 μL pH 4 injections were reduced compared to non-anaesthetized skin (48 ± 9 vs. 79 ± 6 VAS; p < 0.01). The axon reflex flare area did not differ between these zones (7.8 ± 1.4 cm(2) vs. 8.3 ± 0.5 cm(2) ). Histamine iontophoresis still caused pruritus in differentially anaesthetized skin in five of eight subjects (VAS 26 ± 14), whereas itch upon cowhage spicules was absent (VAS 0 vs. 29 ± 11 in non-anaesthetized skin). We conclude that activation of mechano-insensitive nociceptors is sufficient to provoke itch by histamine- and acid-induced pain. The mechano-sensitive nociceptors are crucial for cowhage-induced itch and for the assessment of heat pain thresholds. © 2015 European Pain Federation - EFIC®

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

    PubMed

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

    2015-09-01

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

  13. Derivation and validation of a sensitive IMA cutpoint to predict cardiac events in patients with chest pain.

    PubMed

    Manini, A F; Ilgen, J; Noble, V E; Bamberg, F; Koenig, W; Bohan, J S; Hoffmann, U

    2009-11-01

    In patients with acute chest pain, we derived a cutpoint for ischaemia-modified albumin (IMA) and prospectively validated this cutpoint to predict 30-day major adverse cardiac events (MACEs). We prospectively recruited a derivation cohort (18-month period) to establish a serum IMA cutpoint targeting 80% sensitivity. This was followed by a prospective validation cohort study of emergency department patients with acute chest pain at two university hospitals over a 3-month period. A MACE was defined as myocardial infarction, revascularisation or death at 30-day follow-up. In the derivation cohort of 151 patients, the IMA cutpoint that achieved 80% sensitivity for MACEs was 75 KU/litre. The sensitivity was prospectively validated in 171 patients consecutively enrolled, of whom 106 underwent multiple-biomarker analysis (19.8% MACE rate, 81% sensitivity of IMA). Furthermore, IMA by itself (81%, p<0.01) and in combination with initial highly sensitive cardiac troponin T (hsTnT) (90%, p<0.001) had significantly higher sensitivity than initial hsTnT (29%) for prediction of MACEs. We prospectively validated the sensitive IMA cutpoint of 75 KU/litre with 80% sensitivity for MACEs in patients with acute chest pain. Our data suggest that IMA alone and in combination with initial hsTnT are more sensitive than the initial hsTnT for MACEs.

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

    PubMed Central

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

    2015-01-01

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

  15. High sensitive troponin T in individuals with chest pain of presumed ischemic origin.

    PubMed

    Cuda, Giovanni; Lentini, Margherita; Gallo, Luigia; Lucia, Fortunata G; Giacinto Carinci, Lorenzina; Mancuso, Serafina; Biondi, Rosa A; Sinopoli, Raffaella; Casadonte, Rita; Guzzi, Pietro H; Cannataro, Mario; Mongiardo, Annalisa; Iaconetti, Claudio; Bochicchio, Angela; Curcio, Antonio; Torella, Daniele; Ricci, Pietroantonio; Indolfi, Ciro; Costanzo, Francesco

    2012-06-01

    This study was aimed at assessing the bias of high sensitive cardiac troponin T vs. the standard cardiac troponin T in a selected population with chest pain of presumed cardiac origin. Serum cTnT was determined in 132 patients and in 106 apparently healthy controls by both assays. The hs-cTnT outperformed the standard generation assay by: i) allowing a larger and earlier diagnosis of AMI (74.2 percent vs. 64.3 percent patients resulted positive at the final diagnosis of AMI when tested with the hs-cTnT or the std-cTnT assay, respectively); ii) showing a better time-dependent dynamics in patients with AMI due to a higher precision at low concentrations; iii) identifying, within the controls, 6 subjects in whom a further examination revealed the presence of chronic asymptomatic cardiac ischemia. The results underscore the excellent performance of the hs-cTnT assay in our population. The use of this test can thus be strongly recommended in subjects presenting to the emergency unit with chest pain of presumed ischemic origin in order to increase the probability of earlier diagnosis of AMI, especially in non-STEMI.

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Cohort Removal Induces Changes in Body Temperature, Pain Sensitivity, and Anxiety-Like Behavior.

    PubMed

    Takao, Keizo; Shoji, Hirotaka; Hattori, Satoko; Miyakawa, Tsuyoshi

    2016-01-01

    Mouse behavior is analyzed to elucidate the effects of various experimental manipulations, including gene mutation and drug administration. When the effect of a factor of interest is assessed, other factors, such as age, sex, temperature, apparatus, and housing, are controlled in experiments by matching, counterbalancing, and/or randomizing. One such factor that has not attracted much attention is the effect of sequential removal of animals from a common cage (cohort removal). Here we evaluated the effects of cohort removal on rectal temperature, pain sensitivity, and anxiety-like behavior by analyzing the combined data of a large number of C57BL/6J mice that we collected using a comprehensive behavioral test battery. Rectal temperature increased in a stepwise manner according to the position of sequential removal from the cage, consistent with previous reports. In the hot plate test, the mice that were removed first from the cage had a significantly longer latency to show the first paw response than the mice removed later. In the elevated plus maze, the mice removed first spent significantly less time on the open arms compared to the mice removed later. The results of the present study demonstrated that cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior in mice. Cohort removal also increased the plasma corticosterone concentration in mice. Thus, the ordinal position in the sequence of removal from the cage should be carefully counterbalanced between groups when the effect of experimental manipulations, including gene manipulation and drug administration, are examined using behavioral tests.

  19. Cohort Removal Induces Changes in Body Temperature, Pain Sensitivity, and Anxiety-Like Behavior

    PubMed Central

    Takao, Keizo; Shoji, Hirotaka; Hattori, Satoko; Miyakawa, Tsuyoshi

    2016-01-01

    Mouse behavior is analyzed to elucidate the effects of various experimental manipulations, including gene mutation and drug administration. When the effect of a factor of interest is assessed, other factors, such as age, sex, temperature, apparatus, and housing, are controlled in experiments by matching, counterbalancing, and/or randomizing. One such factor that has not attracted much attention is the effect of sequential removal of animals from a common cage (cohort removal). Here we evaluated the effects of cohort removal on rectal temperature, pain sensitivity, and anxiety-like behavior by analyzing the combined data of a large number of C57BL/6J mice that we collected using a comprehensive behavioral test battery. Rectal temperature increased in a stepwise manner according to the position of sequential removal from the cage, consistent with previous reports. In the hot plate test, the mice that were removed first from the cage had a significantly longer latency to show the first paw response than the mice removed later. In the elevated plus maze, the mice removed first spent significantly less time on the open arms compared to the mice removed later. The results of the present study demonstrated that cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior in mice. Cohort removal also increased the plasma corticosterone concentration in mice. Thus, the ordinal position in the sequence of removal from the cage should be carefully counterbalanced between groups when the effect of experimental manipulations, including gene manipulation and drug administration, are examined using behavioral tests. PMID:27375443

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. 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.

  4. The efficacy of non-surgical treatment on pain and sensitization in patients with knee osteoarthritis: a pre-defined ancillary analysis from a randomized controlled trial.

    PubMed

    Skou, S T; Roos, E M; Simonsen, O; Laursen, M B; Rathleff, M S; Arendt-Nielsen, L; Rasmussen, S

    2016-01-01

    To report the efficacy of a 3-month treatment program consisting of neuromuscular exercise, education, diet, insoles and pain medication (MEDIC-treatment) compared to usual care (two leaflets with information and treatment advice) in reducing pain-related measures and sensitization in patients with knee osteoarthritis (OA) not eligible for total knee replacement (TKR). A pre-defined ancillary analysis of the results at 3 months of a randomized controlled trial (RCT) of 100 patients randomized to MEDIC-treatment or usual care. ClinicalTrials.gov (NCT01535001). Outcomes were sensitization assessed at the knee, the lower leg and forearm using a handheld algometer, peak pain intensity in the previous 24 h, pain intensity after 30 min of walking, pain location and pattern, spreading of pain (a region-divided body chart) and the usage of pain medication. The MEDIC group had larger improvements from baseline to 3 months in peak pain intensity (P = 0.02) and pain after 30 min of walking (P < 0.001) and in the number of body sites with pain (P = 0.04). There was no difference in the change in sensitization from baseline to 3 months between groups (P = 0.87), but sensitization decreased in both groups (P < 0.001). A non-surgical treatment program is more efficacious in reducing pain-related measures than usual care, while both are equally efficacious in reducing sensitization, indicating that mechanisms other than pain sensitization contribute to the perceived pain. The patients did not have severe symptomatic knee OA and hence pain sensitization may not yet have developed into a clinically relevant parameter or subgroups with less sensitization may exist. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2005-07-01

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

  6. 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

  7. Neuro Emotional Technique for the treatment of trigger point sensitivity in chronic neck pain sufferers: a controlled clinical trial.

    PubMed

    Bablis, Peter; Pollard, Henry; Bonello, Rod

    2008-05-21

    Trigger points have been shown to be active in many myofascial pain syndromes. Treatment of trigger point pain and dysfunction may be explained through the mechanisms of central and peripheral paradigms. This study aimed to investigate whether the mind/body treatment of Neuro Emotional Technique (NET) could significantly relieve pain sensitivity of trigger points presenting in a cohort of chronic neck pain sufferers. Sixty participants presenting to a private chiropractic clinic with chronic cervical pain as their primary complaint were sequentially allocated into treatment and control groups. Participants in the treatment group received a short course of Neuro Emotional Technique that consists of muscle testing, general semantics and Traditional Chinese Medicine. The control group received a sham NET protocol. Outcome measurements included pain assessment utilizing a visual analog scale and a pressure gauge algometer. Pain sensitivity was measured at four trigger point locations: suboccipital region (S); levator scapulae region (LS); sternocleidomastoid region (SCM) and temporomandibular region (TMJ). For each outcome measurement and each trigger point, we calculated the change in measurement between pre- and post- treatment. We then examined the relationships between these measurement changes and six independent variables (i.e. treatment group and the above five additional participant variables) using forward stepwise General Linear Model. The visual analog scale (0 to 10) had an improvement of 7.6 at S, 7.2 at LS, 7.5 at SCM and 7.1 at the TMJ in the treatment group compared with no improvement of at S, and an improvement of 0.04 at LS, 0.1 at SCM and 0.1 at the TMJ point in the control group, (P < 0.001). After a short course of NET treatment, measurements of visual analog scale and pressure algometer recordings of four trigger point locations in a cohort of chronic neck pain sufferers were significantly improved when compared to a control group which received

  8. Neuro Emotional Technique for the treatment of trigger point sensitivity in chronic neck pain sufferers: A controlled clinical trial

    PubMed Central

    Bablis, Peter; Pollard, Henry; Bonello, Rod

    2008-01-01

    Background Trigger points have been shown to be active in many myofascial pain syndromes. Treatment of trigger point pain and dysfunction may be explained through the mechanisms of central and peripheral paradigms. This study aimed to investigate whether the mind/body treatment of Neuro Emotional Technique (NET) could significantly relieve pain sensitivity of trigger points presenting in a cohort of chronic neck pain sufferers. Methods Sixty participants presenting to a private chiropractic clinic with chronic cervical pain as their primary complaint were sequentially allocated into treatment and control groups. Participants in the treatment group received a short course of Neuro Emotional Technique that consists of muscle testing, general semantics and Traditional Chinese Medicine. The control group received a sham NET protocol. Outcome measurements included pain assessment utilizing a visual analog scale and a pressure gauge algometer. Pain sensitivity was measured at four trigger point locations: suboccipital region (S); levator scapulae region (LS); sternocleidomastoid region (SCM) and temporomandibular region (TMJ). For each outcome measurement and each trigger point, we calculated the change in measurement between pre- and post- treatment. We then examined the relationships between these measurement changes and six independent variables (i.e. treatment group and the above five additional participant variables) using forward stepwise General Linear Model. Results The visual analog scale (0 to 10) had an improvement of 7.6 at S, 7.2 at LS, 7.5 at SCM and 7.1 at the TMJ in the treatment group compared with no improvement of at S, and an improvement of 0.04 at LS, 0.1 at SCM and 0.1 at the TMJ point in the control group, (P < 0.001). Conclusion After a short course of NET treatment, measurements of visual analog scale and pressure algometer recordings of four trigger point locations in a cohort of chronic neck pain sufferers were significantly improved when

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  11. Evaluation of patients presenting with knee pain: Part I. History, physical examination, radiographs, and laboratory tests.

    PubMed

    Calmbach, Walter L; Hutchens, Mark

    2003-09-01

    Family physicians frequently encounter patients with knee pain. Accurate diagnosis requires a knowledge of knee anatomy, common pain patterns in knee injuries, and features of frequently encountered causes of knee pain, as well as specific physical examination skills. The history should include characteristics of the patient's pain, mechanical symptoms (locking, popping, giving way), joint effusion (timing, amount, recurrence), and mechanism of injury. The physical examination should include careful inspection of the knee, palpation for point tenderness, assessment of joint effusion, range-of-motion testing, evaluation of ligaments for injury or laxity, and assessment of the menisci. Radiographs should be obtained in patients with isolated patellar tenderness or tenderness at the head of the fibula, inability to bear weight or flex the knee to 90 degrees, or age greater than 55 years.

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

    PubMed Central

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

    2014-01-01

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

  13. 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.

  14. Temporal Summation Of Second Pain And Its Maintenance Are Useful For Characterizing Widespread Central Sensitization Of Fibromyalgia Patients

    PubMed Central

    Staud, Roland; Robinson, Michael E.; Price, Donald D.

    2007-01-01

    Temporal summation of second pain (TSSP) results from repetitive stimulation of peripheral C-fibers (> 0.33 Hz) and is thought to reflect summation mechanisms of dorsal horn neurons (i.e., windup). Both TSSP and windup result in short term enhancement of C fiber-evoked responses that decay rapidly after the end of stimulation. However, very low stimulus frequencies (0.17-0.08 Hz) can maintain this enhancement after TSSP and windup have occurred. This maintained enhancement is termed TSSP-maintenance (TSSP-M) and is indicative of central sensitization. TSSP-M may be especially relevant for chronic pain conditions such as fibromyalgia (FM) and may play an important role in its pathogenesis. Whereas TSSP-M of heat induced pain is well characterized in human subjects at spinal cord levels related to the upper body, TSSP-M at spinal levels related to the lower body has not been previously studied. The present study was designed to evoke TSSP-M at the upper and lower extremities of normal controls (NC) and FM patients and thus characterize their spatial distribution of central sensitization. Twenty-three NC and twenty-six FM patients were enrolled in this study. TSSP-M testing consisted of repetitive heat pain stimulation at the thenar eminences of the hands or feet. The subjects rated the pain intensity of repetitive heat stimuli as well as 15 sec and 30 sec pain aftersensations. The experiments demonstrated significant TSSP-M for both NC and FM patients. In contrast to NC, TSSP-M ratings of heat stimuli were increased in FM patients and their TSSP-aftersensations were prolonged. There was, however, no statistical difference between TSSP-M ratings or TSSP-aftersensations at the hands or feet in either NC or FM patients. These findings demonstrate that central sensitization of FM patients is widespread and similar along the spinal neuroaxis. Perspective The pain of FM seems to be accompanied by generalized central sensitization, involving the length of the spinal

  15. Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients.

    PubMed

    Staud, Roland; Robinson, Michael E; Price, Donald D

    2007-11-01

    Temporal summation of second pain (TSSP) results from repetitive stimulation of peripheral C-fibers (>0.33 Hz) and is thought to reflect summation mechanisms of dorsal horn neurons (ie, windup). Both TSSP and windup result in short term enhancement of C fiber-evoked responses that decay rapidly after the end of stimulation. However, very low stimulus frequencies (0.17 to 0.08 Hz) can maintain this enhancement after TSSP and windup have occurred. This maintained enhancement is termed TSSP-maintenance (TSSP-M) and is indicative of central sensitization. TSSP-M may be especially relevant for chronic pain conditions such as fibromyalgia (FM) and may play an important role in its pathogenesis. Whereas TSSP-M of heat induced pain is well-characterized in human subjects at spinal cord levels related to the upper body, TSSP-M at spinal levels related to the lower body has not been previously studied. The present study was designed to evoke TSSP-M at the upper and lower extremities of normal controls (NC) and FM patients and thus characterize their spatial distribution of central sensitization. Twenty-three NC and 26 FM patients were enrolled in this study. TSSP-M testing consisted of repetitive heat pain stimulation at the thenar eminences of the hands or feet. The subjects rated the pain intensity of repetitive heat stimuli as well as 15- and 30-second pain aftersensations. The experiments demonstrated significant TSSP-M for both NC and FM patients. In contrast to NC, TSSP-M ratings of heat stimuli were increased in FM patients and their TSSP-aftersensations (TSSP-AS) were prolonged. There was, however, no statistical difference between TSSP-M ratings or TSSP-AS at the hands or feet in either NC or FM patients. These findings demonstrate that central sensitization of FM patients is widespread and similar along the spinal neuroaxis. The pain of FM seems to be accompanied by generalized central sensitization, involving the length of the spinal neuroaxis. Thus, widespread

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2011-10-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2009-09-01

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

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

    PubMed

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

    2009-03-01

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

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

    PubMed

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

    2015-09-01

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

  2. Quantitative meta-analytic approaches for the systematic synthesis of data and hazard identification: A case study of decreased pain sensitivity due to trimethylbenzene exposure.

    PubMed

    Davis, J Allen; Kraft, Andrew

    2017-10-01

    Traditionally, human health risk assessments have relied on qualitative approaches for hazard identification, which involves weight of evidence determinations that integrate evidence across multiple studies. Recently, the National Research Council has recommended the development of quantitative approaches for evidence integration, including the application of meta-analyses, to help summarize and evaluate the results of a systematic review. In the meta-analytic approach, a pooled effect size is calculated after consideration of multiple potential confounding factors in order to determine whether the entire database under consideration indicates a chemical is a hazard. The following case-study applies qualitative and quantitative approaches to determine whether trimethylbenzene (TMB) isomers represent a neurotoxic hazard, specifically focusing on pain sensitivity. Following a thorough literature search, the only pain sensitivity studies available for TMBs initially seem discordant in their results: effects on pain sensitivity are seen immediately after termination of exposure, appear to resolve 24h after exposure, and then reappear 50 days later following foot-shock. Qualitative consideration of toxicological and toxicokinetic characteristics of the TMB isomers suggests that the observed differences between studies are likely due to testing time and the application of external stressors. Meta-analyses and -regressions support this conclusion: when all studies are included and possible confounders (isomer, testing time, laboratory, etc.) are accounted for, the pooled effect sizes are statistically significant, thus supporting that TMBs are a possible neurotoxic hazard to human health. Ultimately, this case study demonstrates how qualitative and quantitative methods can be combined to provide a robust hazard identification analysis by incorporating more of the available information. Published by Elsevier Inc.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2007-06-14

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

  5. 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.

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

    PubMed

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

    2014-03-20

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2011-12-01

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

  9. Evidence of central sensitisation in those with dry eye symptoms and neuropathic-like ocular pain complaints: incomplete response to topical anaesthesia and generalised heightened sensitivity to evoked pain.

    PubMed

    Crane, Ashley M; Feuer, William; Felix, Elizabeth R; Levitt, Roy C; McClellan, Allison L; Sarantopoulos, Konstantinos D; Galor, Anat

    2017-09-01

    To evaluate how closely neuropathic-like ocular pain (NOP) symptoms align with a metric of central sensitisation (ie, the presence of persistent ocular pain after topical anaesthetic placement) in individuals with dry eye (DE) symptoms. Cross-sectional study of 224 individuals with DE symptoms seen in the Miami Veterans Affairs eye clinic. An evaluation was performed consisting of questionnaires regarding DE symptoms, NOP descriptors and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Subsequent analyses were performed to examine for differences between those with and without ocular pain after topical anaesthetic placement. The mean age was 62 years with 91% being men. DE symptoms and NOP symptoms were higher in subjects with persistent ocular pain after anaesthesia. Most DE signs were not related to persistent pain, with the exception of meibum quality. Individuals with persistent ocular pain also demonstrated greater sensitivity to evoked pain at testing sites on the forehead and forearm. When examining receiver operator characteristic curves considering persistent pain as a gold standard for central sensitisation within the corneal pathway, intensity of ocular pain ratings, Ocular Surface Disease Index scores and sensitivity to light provided the most robust relationships, each with an area under the curve of 0.72. Individuals with DE symptoms and persistent ocular pain after topical proparacaine (a marker of central sensitisation to pain) more frequently report NOP-like symptoms and demonstrate increased sensitivity to evoked pain. 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/.

  10. 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.

  11. The Development of a Culturally Sensitive Pediatric Pain Management Intervention for African American Adolescents With Sickle Cell Disease

    PubMed Central

    Schwartz, Lisa A.; Radcliffe, Jerilynn; Barakat, Lamia P.

    2009-01-01

    This article describes a cognitive-behavioral pain management intervention for adolescents with sickle cell disease with particular emphasis on description of components that enhance its cultural sensitivity. To date, 25 participants have been randomized to the pain management intervention. Treatment expectation ratings at baseline and midpoint (after Session 2) and participant feedback regarding interest in, enjoyment of, and helpfulness of the intervention are presented. Preliminary data indicate that most of the participants have been engaged in and have responded well to the intervention. Challenges of the intervention are discussed. PMID:19718272

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

    PubMed

    Miller, A L; Leach, M C

    2015-04-01

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

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

    PubMed

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

    2014-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed

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

    2013-09-01

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

  16. Differences in Topographical Pressure Pain Sensitivity Maps of the Scalp Between Patients With Migraine and Healthy Controls.

    PubMed

    Barón, Johanna; Ruiz, Marina; Palacios-Ceña, María; Madeleine, Pascal; Guerrero, Ángel L; Arendt-Nielsen, Lars; Fernández-de-Las-Peñas, César

    2017-02-01

    To investigate differences in topographical pressure pain sensitivity maps of the scalp between patients with migraine and healthy controls considering the chronicity (episodic/chronic) and side (strictly unilateral/bilateral) of the symptoms. It seems that the trigeminal area is sensitized in migraine. No study has investigated topographical pressure sensitivity maps of the scalp in patients with migraine. Pressure pain thresholds (PPTs) were assessed from 21 points distributed over the scalp in 86 patients with episodic migraine, 76 with chronic migraine, and 42 healthy age and matched healthy controls in a blinded design. Topographical pressure pain sensitivity maps based on interpolation of the PPTs were constructed. Clinical features of migraine, anxiety, and depression (Hospital Anxiety and Depression Scale, HADS) were collected. The multivariate ANCOVA revealed significant differences in PPT between points (F = 55.674; P < .001) and groups (F = 5.316; P = .006), but not sides (F = 0.880; P = .417). No significant effect of gender (F = 0.897; P = .656), depression (F = 1.109; P = .220), or anxiety (F = 0.981; F = 0.569) was found. Post hoc comparisons revealed: (1) lower PPTs in both migraine groups than in healthy controls in all points (P < .001); (2) no significant differences between chronic or episodic migraine (P > .335) except for Fp1 (P = .045) and Fp2 (P = .017) points where subjects with chronic migraine had lower PPTs than those with episodic migraine; (3) no differences between bilateral/unilateral migraine (P > .417). An anterior to posterior gradient was found, with the lowest PPTs located in frontal regions and the highest PPTs in occipital areas (all groups, P < .001). We found that patients with migraine exhibited generalized pressure pain hypersensitivity in the head as compared to healthy controls and that hypersensitivity was similar between episodic/chronic and

  17. 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.

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

    PubMed

    Becker, Susanne; Kleinböhl, Dieter; Hölzl, Rupert

    2012-09-01

    Regarding awareness as a consistent concept has contributed to the controversy about implicit learning. The present study emphasized the importance of distinguishing aspects of awareness in order to determine whether learning is implicit. By decomposing awareness into awareness of contingencies, of the procedure being a learning task, and of the reinforcing stimuli, it was demonstrated that implicit operant learning modulated pain sensitivity. All of these aspects of awareness were demonstrated to not be necessary for learning. Additionally, discrimination of contingencies was not necessary on different levels of processing as demonstrated by a verbal and a behavioral method. It was demonstrated that explicit cognitive processes about one's own behavior, impaired learning, even though these cognitions were not immediately related to the learning process. The results of this study are of special interest in the context of pain, since implicit operant learning can explain the gradual development of hypersensitivity in chronic pain. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

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

    PubMed

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

    2017-08-01

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

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

    PubMed

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

    2011-04-01

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

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

    PubMed Central

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

    2011-01-01

    There is considerable interest in Gray’s reinforcement sensitivity theory. However, few measures of the behavioral approach (BAS) and inhibition systems (BIS) exist for children. Moreover, the theory was substantially revised a decade ago and measurement instruments are still largely based on the old theory. Our aim was to revise questionnaire and laboratory assessments of BIS and BAS for children. Performance on the Point Scoring Reaction Time Task for Children Revised (PSRTT-CR) conformed to theoretical expectations. Caregiver reports of BIS and BAS were associated with corresponding PSRTT-CR indices, suggesting cross-method convergent and discriminant validity. There was convergence with physiological correlates of BAS, but not physiological correlates of BIS. Overall, our revised measures represent promising instruments of children’s BIS and BAS. PMID:21603055

  6. Peripheral Calcitonin Gene-Related Peptide Receptor Activation and Mechanical Sensitization of the Joint in Rat Models of Osteoarthritis Pain

    PubMed Central

    Bullock, Craig M; Wookey, Peter; Bennett, Andrew; Mobasheri, Ali; Dickerson, Ian; Kelly, Sara

    2014-01-01

    Objective To investigate the role of the sensory neuropeptide calcitonin gene-related peptide (CGRP) in peripheral sensitization in experimental models of osteoarthritis (OA) pain. Methods Experimental knee OA was induced in rats by intraarticular injection of monosodium iodoacetate (MIA) or by transection of the medial meniscus (MMT). Single-unit recordings of joint-innervating nociceptors were obtained in MIA- and saline-treated rats following administration of CGRP or the CGRP receptor antagonist CGRP 8–37. Effects of CGRP 8–37 were also examined in rats that underwent MMT and sham operations. Protein and messenger RNA (mRNA) levels of CGRP receptor components in the L3–L4 dorsal root ganglion (DRG) were investigated following MIA treatment. Results In both the MIA and MMT groups, the mechanical sensitivity of joint nociceptors was enhanced compared to that in the control groups. Exogenous CGRP increased mechanical sensitivity in a greater proportion of joint nociceptors in the MIA-treated rats than in the saline-treated rats. Local blockade of endogenous CGRP by CGRP 8–37 reversed both the MIA- and MMT-induced enhancement of joint nociceptor responses. Joint afferent cell bodies coexpressed the receptor for CGRP, called the calcitonin-like receptor (CLR), and the intracellular accessory CGRP receptor component protein. MIA treatment increased the levels of mRNA for CLR in the L3–L4 DRG and the levels of CLR protein in medium and large joint afferent neurons. Conclusion Our findings provide new and compelling evidence implicating a role of CGRP in peripheral sensitization in experimental OA. Our novel finding of CGRP-mediated control of joint nociceptor mechanosensitivity suggests that the CGRP receptor system may be an important target for the modulation of pain during OA. CGRP receptor antagonists recently developed for migraine pain should be investigated for their efficacy against pain in OA. PMID:24719311

  7. Post-operative orofacial pain, temporomandibular dysfunction and trigeminal sensitivity after recent pterional craniotomy: preliminary study.

    PubMed

    Brazoloto, Thiago Medina; de Siqueira, Silvia Regina Dowgan Tesseroli; Rocha-Filho, Pedro Augusto Sampaio; Figueiredo, Eberval Gadelha; Teixeira, Manoel Jacobsen; de Siqueira, José Tadeu Tesseroli

    2017-05-01

    Surgical trauma at the temporalis muscle is a potential cause of post-craniotomy headache and temporomandibular disorders (TMD). The aim of this study was to evaluate the prevalence of pain, masticatory dysfunction and trigeminal somatosensory abnormalities in patients who acquired aneurysms following pterional craniotomy. Fifteen patients were evaluated before and after the surgical procedure by a trained dentist. The evaluation consisted of the (1) research diagnostic criteria for TMD, (2) a standardized orofacial pain questionnaire and (3) a systematic protocol for quantitative sensory testing (QST) for the trigeminal nerve. After pterional craniotomy, 80% of the subjects, 12 patients, developed orofacial pain triggered by mandibular function. The pain intensity was measured by using the visual analog scale (VAS), and the mean pain intensity was 3.7. The prevalence of masticatory dysfunction was 86.7%, and there was a significant reduction of the maximum mouth opening. The sensory evaluation showed tactile and thermal hypoesthesia in the area of pterional access in all patients. There was a high frequency of temporomandibular dysfunction, postoperative orofacial pain and trigeminal sensory abnormalities. These findings can help to understand several abnormalities that can contribute to postoperative headache or orofacial pain complaints after pterional surgeries.

  8. The validity of temperature-sensitive ingestible capsules for measuring core body temperature in laboratory protocols.

    PubMed

    Darwent, David; Zhou, Xuan; van den Heuvel, Cameron; Sargent, Charli; Roach, Greg D

    2011-10-01

    The human core body temperature (CBT) rhythm is tightly coupled to an endogenous circadian pacemaker located in the suprachiasmatic nucleus of the anterior hypothalamus. The standard method for assessing the status of this pacemaker is by continuous sampling of CBT using rectal thermometry. This research sought to validate the use of ingestible, temperature-sensitive capsules to measure CBT as an alternative to rectal thermometry. Participants were 11 young adult males who had volunteered to complete a laboratory protocol that extended across 12 consecutive days. A total of 87 functional capsules were ingested and eliminated by participants during the laboratory internment. Core body temperature samples were collected in 1-min epochs and compared to paired samples collected concurrently via rectal thermistors. Agreement between samples that were collected using ingestible sensors and rectal thermistors was assessed using the gold-standard limits of agreement method. Across all valid paired samples collected during the study (n = 120,126), the mean difference was 0.06°C, whereas the 95% CI (confidence interval) for differences was less than ±0.35°C. Despite the overall acceptable limits of agreement, systematic measurement bias was noted across the initial 5 h of sensor-transit periods and attributed to temperature gradations across the alimentary canal.

  9. Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents.

    PubMed

    Okun, Alec; DeFelice, Milena; Eyde, Nathan; Ren, Jiyang; Mercado, Ramon; King, Tamara; Porreca, Frank

    2011-01-10

    Tissue injury elicits both hypersensitivity to evoked stimuli and ongoing, stimulus-independent pain. We previously demonstrated that pain relief elicits reward in nerve-injured rats. This approach was used to evaluate the temporal and mechanistic features of inflammation-induced ongoing pain. Intraplantar Complete Freund's Adjuvant (CFA) produced thermal hyperalgesia and guarding behavior that was reliably observed within 24 hrs and maintained, albeit diminished, 4 days post-administration. Spinal clonidine produced robust conditioned place preference (CPP) in CFA treated rats 1 day, but not 4 days following CFA administration. However, spinal clonidine blocked CFA-induced thermal hyperalgesia at both post-CFA days 1 and 4, indicating different time-courses of ongoing and evoked pain. Peripheral nerve block by lidocaine administration into the popliteal fossa 1 day following intraplantar CFA produced a robust preference for the lidocaine paired chamber, indicating that injury-induced ongoing pain is driven by afferent fibers innervating the site of injury. Pretreatment with resiniferatoxin (RTX), an ultrapotent capsaicin analogue known to produce long-lasting desensitization of TRPV1 positive afferents, fully blocked CFA-induced thermal hypersensitivity and abolished the CPP elicited by administration of popliteal fossa lidocaine 24 hrs post-CFA. In addition, RTX pretreatment blocked guarding behavior observed 1 day following intraplantar CFA. In contrast, administration of the selective TRPV1 receptor antagonist, AMG9810, at a dose that reversed CFA-induced thermal hyperalgesia failed to reduce CFA-induced ongoing pain or guarding behavior. These data demonstrate that inflammation induces both ongoing pain and evoked hypersensitivity that can be differentiated on the basis of time course. Ongoing pain (a) is transient, (b) driven by peripheral input resulting from the injury, (c) dependent on TRPV1 positive fibers and (d) not blocked by TRPV1 receptor antagonism

  10. Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target?

    PubMed

    Nijs, Jo; Meeus, Mira; Versijpt, Jan; Moens, Maarten; Bos, Inge; Knaepen, Kristel; Meeusen, Romain

    2015-04-01

    Central sensitization is a form of maladaptive neuroplasticity underlying many chronic pain disorders, including neuropathic pain, fibromyalgia, whiplash, headache, chronic pelvic pain syndrome and some forms of osteoarthritis, low back pain, epicondylitis, shoulder pain and cancer pain. Brain-derived neurotrophic factor (BDNF) is a driving force behind neuroplasticity, and it is therefore crucial for neural maintenance and repair. However, BDNF also contributes to sensitization of pain pathways, making it an interesting novel therapeutic target. An overview of BDNF's sensitizing capacity at every level of the pain pathways is presented, including the peripheral nociceptors, dorsal root ganglia, spinal dorsal horn neurons, and brain descending inhibitory and facilitatory pathways. This is followed by the presentation of several potential therapeutic options, ranging from indirect influencing of BDNF levels (using exercise therapy, anti-inflammatory drugs, melatonin, repetitive transcranial magnetic stimulation) to more specific targeting of BDNF's receptors and signaling pathways (blocking the proteinase-activated receptors 2-NK-κβ signaling pathway, administration of phencyclidine for antagonizing NMDA receptors, or blockade of the adenosine A2A receptor). This section focuses on combining pharmacotherapy with multimodal rehabilitation for balancing the deleterious and therapeutic effects of BNDF treatment in chronic pain patients, as well as accounting for the complex and biopsychosocial nature of chronic pain.

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

    PubMed

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

    2016-10-11

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

  12. Giardiasis: an update review on sensitivity and specificity of methods for laboratorial diagnosis.

    PubMed

    Soares, Renata; Tasca, Tiana

    2016-10-01

    Giardiasis is a major cause of diarrhoea transmitted by ingestion of contaminated water and food with cysts, and it has been spread among people with poor oral hygiene. The traditional diagnosis is performed by identifying trophozoites and cysts of Giardia duodenalis through microscopy of faecal samples. In addition to microscopy, different methods have been validated for giardiasis diagnosis which are based on immunologic and molecular analyses. The aim of this study was to conduct a review of the main methods applied in clinical laboratory for diagnosis of giardiasis, in the last 10years, regarding the specificity and sensitivity criteria. It was observed high variability in the performance of the same methodology across studies; however, several techniques have been considered better than microscopy. The later, although gold standard, presents low sensitivity in cases of low number of cysts in the sample, and the experience of the microscopist must also be considered. We conclude that microscopy should still be held and complementary technique is recommended, in order to provide a reliable diagnosis and a proper treatment of the patient. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed Central

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

    2009-01-01

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

  19. 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

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

    PubMed

    Hoffman, Donna

    2015-01-01

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

  1. Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents

    PubMed Central

    2011-01-01

    Background Tissue injury elicits both hypersensitivity to evoked stimuli and ongoing, stimulus-independent pain. We previously demonstrated that pain relief elicits reward in nerve-injured rats. This approach was used to evaluate the temporal and mechanistic features of inflammation-induced ongoing pain. Results Intraplantar Complete Freund's Adjuvant (CFA) produced thermal hyperalgesia and guarding behavior that was reliably observed within 24 hrs and maintained, albeit diminished, 4 days post-administration. Spinal clonidine produced robust conditioned place preference (CPP) in CFA treated rats 1 day, but not 4 days following CFA administration. However, spinal clonidine blocked CFA-induced thermal hyperalgesia at both post-CFA days 1 and 4, indicating different time-courses of ongoing and evoked pain. Peripheral nerve block by lidocaine administration into the popliteal fossa 1 day following intraplantar CFA produced a robust preference for the lidocaine paired chamber, indicating that injury-induced ongoing pain is driven by afferent fibers innervating the site of injury. Pretreatment with resiniferatoxin (RTX), an ultrapotent capsaicin analogue known to produce long-lasting desensitization of TRPV1 positive afferents, fully blocked CFA-induced thermal hypersensitivity and abolished the CPP elicited by administration of popliteal fossa lidocaine 24 hrs post-CFA. In addition, RTX pretreatment blocked guarding behavior observed 1 day following intraplantar CFA. In contrast, administration of the selective TRPV1 receptor antagonist, AMG9810, at a dose that reversed CFA-induced thermal hyperalgesia failed to reduce CFA-induced ongoing pain or guarding behavior. Conclusions These data demonstrate that inflammation induces both ongoing pain and evoked hypersensitivity that can be differentiated on the basis of time course. Ongoing pain (a) is transient, (b) driven by peripheral input resulting from the injury, (c) dependent on TRPV1 positive fibers and (d) not

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

    PubMed

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

    2011-07-15

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

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

    PubMed

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

    2003-09-01

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

  4. 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 ...

  5. 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.

  6. 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

  7. Immediate effects of spinal manipulation on thermal pain sensitivity: an experimental study.

    PubMed

    George, Steven Z; Bishop, Mark D; Bialosky, Joel E; Zeppieri, Giorgio; Robinson, Michael E

    2006-08-15

    The underlying causes of spinal manipulation hypoalgesia are largely unknown. The beneficial clinical effects were originally theorized to be due to biomechanical changes, but recent research has suggested spinal manipulation may have a direct neurophysiological effect on pain perception through dorsal horn inhibition. This study added to this literature by investigating whether spinal manipulation hypoalgesia was: a) local to anatomical areas innervated by the lumbar spine; b) correlated with psychological variables; c) greater than hypoalgesia from physical activity; and d) different for A-delta and C-fiber mediated pain perception. Asymptomatic subjects (n = 60) completed baseline psychological questionnaires and underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception. Subjects were then randomized to ride a stationary bicycle, perform lumbar extension exercise, or receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes after the intervention period. Data were analyzed with repeated measures ANOVA and post-hoc testing was performed with Bonferroni correction, as appropriate. Subjects in the three intervention groups did not differ on baseline characteristics. Hypoalgesia from spinal manipulation was observed in lumbar innervated areas, but not control (cervical innervated) areas. Hypoalgesic response was not strongly correlated with psychological variables. Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ from stationary bicycle and lumbar extension (p > 0.05). Spinal manipulation hypoalgesia for C-fiber mediated pain perception was greater than stationary bicycle riding (p = 0.040), but not for lumbar extension (p = 0.105). Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic mechanism of spinal manipulation for asymptomatic subjects, but further study is required to replicate this finding in subjects with low back pain.

  8. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    1999-01-01

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

  11. Diffraction-based sensitivity analysis for an external occulter laboratory demonstration.

    PubMed

    Sirbu, Dan; Kim, Yunjong; Jeremy Kasdin, N; Vanderbei, Robert J

    2016-08-01

    An external flower-shaped occulter flying in formation with a space telescope can theoretically provide sufficient starlight suppression to enable direct imaging of an Earth-like planet. Occulter shapes are scaled to enable experimental validation of their performance at laboratory dimensions. Previous experimental results have shown promising performance but have not realized the full theoretical potential of occulter designs. Here, we develop a two-dimensional diffraction model for optical propagations for occulters incorporating experimental errors. We perform a sensitivity analysis, and comparison with experimental results from a scaled-occulter testbed validates the optical model to the 10-10 contrast level. The manufacturing accuracy along the edge of the occulter shape is identified as the limiting factor to achieving the theoretical potential of the occulter design. This hypothesis is experimentally validated using a second occulter mask manufactured with increased edge feature accuracy and resulting in a measured contrast level approaching the 10-12 level-a better than one order of magnitude improvement in performance.

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

    PubMed Central

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

    2017-01-01

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

  13. Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization? A study of healthy volunteers - design and detailed plan of analysis.

    PubMed

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

    2016-05-31

    Several factors are believed to influence the development and experience of pain. Human clinical pain models are central tools, in the investigation of basic physiologic pain responses, and can be applied in patients as well as in healthy volunteers. Each clinical pain model investigates different aspects of the human pain response. Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated with the size of the area of secondary hyperalgesia induced by the clinical heat pain model: Brief thermal sensitization. We aim to include 120 healthy participants. The participants will be tested on two separate study days with the following procedures: i) Brief thermal sensitization, ii) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires. We conducted statistical simulations based on data from our previous study, to estimate an empirical power of 99.9 % with α of 0.05. We define that an R(2) < 0.25 and predictive intervals larger than +/-150 cm(2) are indications of a weak association. The area of secondary hyperalgesia may serve as a quantitative measure of the central sensitization induced by cutaneous heat stimulation, and thus may be a biomarker of an individual's pain sensitivity. The number of studies investigating secondary hyperalgesia is growing; however basic knowledge of the physiologic aspects of secondary hyperalgesia in

  14. Validity, reliability, and assessment sensitivity of the Japanese version of the short-form McGill pain questionnaire 2 in Japanese patients with neuropathic and non-neuropathic pain.

    PubMed

    Maruo, Tomoyuki; Nakae, Aya; Maeda, Lynn; Shi, Kenrin; Takahashi, Kayoko; Morris, Shayne; Hosomi, Koichi; Kanatani, Hiroshi; Matsuzaki, Taiga; Saitoh, Youichi

    2014-11-01

    The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2-J). This is a cross-sectional study. The original SF-MPQ-2 was translated into Japanese to create the SF-MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF-MPQ-2-J was assessed using internal consistency, reliability coefficients (Cronbach's α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis (CFA) was also performed to test the theoretical structure of the SF-MPQ-2-J. The internal consistencies calculated included continuous pain, α=0.893; intermittent pain, α=0.875; predominantly neuropathic pain, α=0.917; affective descriptors, α=0.857; and total score, α=0.907. The reproducibility coefficients calculated included continuous pain, ρ=0.81; intermittent pain, ρ=0.78; predominantly neuropathic pain, ρ=0.85; affective descriptors, ρ=0.75; and total score, ρ=0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. These findings suggest that the reliability and validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross-cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain. Wiley Periodicals, Inc.

  15. Nociceptive Sensitizers Are Regulated in Damaged Joint Tissues, Including Articular Cartilage, When Osteoarthritic Mice Display Pain Behavior

    PubMed Central

    Driscoll, Clare; Chanalaris, Anastasios; Knights, Chancie; Ismail, Heba; Sacitharan, Pradeep K.; Gentry, Clive; Bevan, Stuart

    2016-01-01

    Objective Pain is the most common symptom of osteoarthritis (OA), yet where it originates in the joint and how it is driven are unknown. The aim of this study was to identify pain‐sensitizing molecules that are regulated in the joint when mice subjected to surgical joint destabilization develop OA‐related pain behavior, the tissues in which these molecules are being regulated, and the factors that control their regulation. Methods Ten‐week‐old mice underwent sham surgery, partial meniscectomy, or surgical destabilization of the medial meniscus (DMM). Pain‐related behavior as determined by a variety of methods (testing of responses to von Frey filaments, cold plate testing for cold sensitivity, analgesiometry, incapacitance testing, and forced flexion testing) was assessed weekly. Once pain‐related behavior was established, RNA was extracted from either whole joints or microdissected tissue samples (articular cartilage, meniscus, and bone). Reverse transcription–polymerase chain reaction analysis was performed to analyze the expression of 54 genes known to regulate pain sensitization. Cartilage injury assays were performed using avulsed immature hips from wild‐type or genetically modified mice or by explanting articular cartilage from porcine joints preinjected with pharmacologic inhibitors. Levels of nerve growth factor (NGF) protein were measured by enzyme‐linked immunosorbent assay. Results Mice developed pain‐related behavior 8 weeks after undergoing partial meniscectomy or 12 weeks after undergoing DMM. NGF, bradykinin receptors B1 and B2, tachykinin, and tachykinin receptor 1 were significantly regulated in the joints of mice displaying pain‐related behavior. Little regulation of inflammatory cytokines, leukocyte activation markers, or chemokines was observed. When tissue samples from articular cartilage, meniscus, and bone were analyzed separately, NGF was consistently regulated in the articular cartilage. The other pain sensitizers were

  16. 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

  17. Immediate changes in pressure pain sensitivity after thoracic spinal manipulative therapy in patients with subacromial impingement syndrome: A randomized controlled study.

    PubMed

    Kardouni, Joseph R; Shaffer, Scott W; Pidcoe, Peter E; Finucane, Sheryl D; Cheatham, Seth A; Michener, Lori A

    2015-08-01

    Thoracic SMT can improve symptoms in patients with subacromial impingement syndrome. However, at this time the mechanisms of SMT are not well established. It is possible that changes in pain sensitivity may occur following SMT. To assess the immediate pain response in patients with shoulder pain following thoracic spinal manipulative therapy (SMT) using pressure pain threshold (PPT), and to assess the relationship of change in pain sensitivity to patient-rated outcomes of pain and function following treatment. Randomized Controlled Study. Subjects with unilateral subacromial impingement syndrome (n = 45) were randomly assigned to receive treatment with thoracic SMT or sham thoracic SMT. PPT was measured at the painful shoulder (deltoid) and unaffected regions (contralateral deltoid and bilateral lower trapezius areas) immediately pre- and post-treatment. Patient-rated outcomes were pain (numeric pain rating scale - NPRS), function (Pennsylvania Shoulder Score - Penn), and global rating of change (GROC). There were no significant differences between groups in pre-to post-treatment changes in PPT (p ≥ 0.583) nor were there significant changes in PPT within either group (p ≥ 0.372) following treatment. NPRS, Penn and GROC improved across both groups (p < 0.001), but there were no differences between the groups (p ≥ 0.574). There were no differences in pressure pain sensitivity between participants receiving thoracic SMT versus sham thoracic SMT. Both groups had improved patient-rated pain and function within 24-48 h of treatment, but there was no difference in outcomes between the groups. Published by Elsevier Ltd.

  18. Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study.

    PubMed

    Nielsen, Lecia Møller; Olesen, Anne Estrup; Sato, Hiroe; Christrup, Lona Louring; Drewes, Asbjørn Mohr

    2016-10-01

    The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental pain model in 40 healthy participants aged 20-65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non-carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. 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.

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

    PubMed

    Matak, Ivica; Rossetto, Ornella; Lacković, Zdravko

    2014-08-01

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

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

    PubMed

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

    2008-05-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

  6. An improvement of mechanical pain sensitivity measurement method: the smaller sized probes may detect heterogeneous sensory threshold in healthy male subjects.

    PubMed

    Duan, Guangyou; Xiang, Guifang; Zhang, Xianwei; Guo, Shanna; Zhang, Yuhao

    2014-02-01

    On the basis of our experience in the application of the mechanical algometer and a number of pilot experiments, we speculated that 0.1- and 0.01-cm(2) probes might improve the measurement of mechanical pain sensitivity relative to the conventional 1-cm(2) probe. Here, we examined the accuracy, feasibility, and applicability of these probes in detecting the mechanical pain sensitivity. Mechanical pain threshold and tolerance tests were performed on subjects using the three probes of 1, 0.1, and 0.01 cm(2) in random order. We compared the application of these probes. The study was set at the Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Fifty healthy male Han Chinese subjects were recruited. We compared the qualities of stimulus-evoked pain, test stability, the measuring time, the subjects' acceptance level of the procedure, the validity of pain measurement, and the arduousness of the task for the investigator among the three different size probes. Compared with the conventional 1-cm(2) probe, the 0.01- and 0.1-cm(2) probes resulted in the subjects responding to stimulus-evoked pain more quickly, accurately, and consistently, and also made the measurement more comfortable for investigators. Up to 80% of the subjects reported the pain quality as a pricking sensation when the 0.01-cm(2) probe was used. The use of the 0.1-cm(2) probe might be more suitable as an optimized method for the detection of pressure pain sensitivity in clinical studies. In addition, the 0.01-cm(2) probe could potentially serve as an alternative to the weighted needle pinprick, providing continuous quantizing detection for pricking pain sensitivity. Wiley Periodicals, Inc.

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

    PubMed

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

    2015-03-01

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

  8. The Effect of Preoperative Intra-Articular Methylprednisolone on Pain After TKA: A Randomized Double-Blinded Placebo Controlled Trial in Patients With High-Pain Knee Osteoarthritis and Sensitization.

    PubMed

    Luna, Iben E; Kehlet, Henrik; Jensen, Claus M; Christiansen, Thorbjørn G; Lind, Thomas; Stephensen, Snorre L; Aasvang, Eske K

    2017-08-24

    In a randomized, double-blind, placebo controlled trial, we investigated the postoperative analgesic effect of a single intra-articular injection of 40 mg methylprednisolone acetate (MP) administered 1 week before total knee arthroplasty (TKA). Forty-eight patients with high pain osteoarthritis (≥5 on a numeric rating scale during walk) and sensitization (pressure pain threshold <250 kPa), aged 50 to 80 years and scheduled for primary unilateral TKA under spinal anaesthesia were included. The primary outcome was the proportion of patients with moderate/severe pain during a 5-m walk test 24 hours postoperatively. Secondary outcomes included pain at 48 hours, during the first 14 days, sensitization (quantitative sensory testing with pressure pain threshold and wind-up from temporal summation), and inflammatory changes (systemic C-reactive protein, intra-articular interleukin [IL]-6). No difference in the proportion of patients with moderate/severe pain was found between MP/placebo groups at 24 hours (67% and 74%, χ(2) = .2, P = .63, odds ratio = .7, 95% confidence interval = .2-2.8) or at 48 hours (57% and 68%, χ(2) = .5, P = .46, odds ratio = .6, 95% confidence interval = .2-2.3), and no difference between groups in postoperative sensitization was found (P > .4) despite reduced preoperative intra-articular inflammation (IL-6) in the MP group versus placebo (median change in IL-6 = -70 pg/mL, interquartile range = -466 to 0 vs. 32 pg/mL, interquartile range = -26 to 75, P = .029). Alternative central or peripheral analgesic interventions in this high-risk group are required. Peripherally driven inflammatory pain and nociceptive changes before TKA has been suggested to be a cause for increased acute postoperative pain. However, preoperative intra-articular MP in patients with high pain osteoarthritis and sensitization did not reduce acute post-TKA pain or sensitization despite a preoperative reduction of intra-articular inflammatory

  9. Utility and sensitivity of the sore throat pain model: results of a randomized controlled trial on the COX-2 selective inhibitor valdecoxib.

    PubMed

    Schachtel, Bernard P; Pan, Sharon; Kohles, Joseph D; Sanner, Kathleen M; Schachtel, Emily P; Bey, Mary

    2007-07-01

    The sore throat pain model was employed in this randomized, placebo-controlled trial to examine the sensitivity of the model in testing the efficacy of valdecoxib as an acute analgesic drug. Changes were made to the study design by employing a different diagnostic index for tonsillo-pharyngitis, a different rating scale (derived from Lasagna's pain thermometer), and alternative analyses, individual responder rates. Under double-blind conditions, 197 patients with painful pharyngitis were randomly allocated to valdecoxib 20 mg bid (n = 65), valdecoxib 40 mg qd (n = 66), or placebo (n = 66) for 24 hours. The expanded Tonsillo-Pharyngitis Assessment and the Lasagna Pain Scale were validated as sensitive study instruments. Both dosage regimens provided significantly greater pain relief compared with placebo on standard efficacy measures over the 24-hour study (all P < .05). Tests for individual response (eg, percentage of patients with at least moderate relief) confirmed these results, and other response rates identified the high sensitivity of the model itself (eg, only 5% of placebo-treated patients achieved >or=50% of maximum total pain relief over 6 hours). These findings indicate that sore throat is a sensitive model to assess analgesic efficacy.

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

    PubMed

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

    2012-06-01

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

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

    PubMed

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

    2014-12-18

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

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

    PubMed

    Etherton, Joseph L; Tapscott, Brian E

    2015-01-01

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

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

    PubMed

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

    2014-04-01

    Recent findings suggest that certain individuals with musculoskeletal pain conditions have increased sensitivity to physical activity (SPA) and respond to activities of stable intensity with increasingly severe pain. This study aimed to determine the degree to which individuals with knee osteoarthritis (OA) show heightened SPA in response to a standardized walking task and whether SPA cross-sectionally predicts psychological factors, responses to quantitative sensory testing (QST), and different OA-related outcomes. One hundred seven adults with chronic knee OA completed self-report measures of pain, function, and psychological factors, underwent QST, and performed a 6-min walk test. Participants rated their discomfort levels throughout the walking task; an index of SPA was created by subtracting first ratings from peak ratings. Repeated-measure analysis of variance revealed that levels of discomfort significantly increased throughout the walking task. A series of hierarchical regression analyses determined that after controlling for significant covariates, psychological factors, and measures of mechanical pain sensitivity, individual variance in SPA predicted self-report pain and function and performance on the walking task. Analyses also revealed that both pain catastrophizing and the temporal summation of mechanical pain were significant predictors of SPA and that SPA mediated the relationship between catastrophizing and self-reported pain and physical function. The discussion addresses the potential processes contributing to SPA and the role it may play in predicting responses to different interventions for musculoskeletal pain conditions. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2005-07-19

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed

    Yarushkina, N I; Filaretova, L P

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2010-09-17

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

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

    PubMed

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

    2010-09-17

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