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Sample records for laboratory pain sensitivity

  1. Relationships among Anxious Symptomatology, Anxiety Sensitivity and Laboratory Pain Responsivity in Children

    PubMed Central

    Tsao, Jennie C. I.; Lu, Qian; Kim, Su C.; Zeltzer, Lonnie K.

    2006-01-01

    Existing laboratory-based research in adult samples has suggested that anxiety sensitivity (AS) increases an individual’s propensity to experience pain-related anxiety which in turn enhances pain responsivity. Such relationships have not been examined in younger populations. Thus, the present study used structural equation modeling (SEM) to test a conceptual model in which AS would evidence an indirect relationship with pain intensity via its contribution to state-specific anticipatory anxiety in relation to a variety of laboratory pain tasks (cold pressor, thermal heat, and pressure pain) in 234 healthy children (116 girls; mean age = 12.6 years, range = 8–18 years). The model further hypothesized that existing anxious symptomatology would demonstrate a direct relationship with pain intensity. Results of the SEM supported the proposed conceptual model with the total indirect effect of AS accounting for 29% of the variance in laboratory pain intensity via its effects on pain-related anticipatory anxiety. AS did not however, evidence a direct relationship with pain intensity. Anxious symptomatology on the other hand, demonstrated a significant direct effect on pain intensity, accounting for 15% of variance. The combined effects of AS, anxiety symptoms, and anticipatory anxiety together explained 62% of the variance in pain intensity. These relationships did not differ for boys and girls indicating no moderating effect of sex in the proposed model. The present results support the potential benefit of assessing both AS and anxiety symptoms in children prior to undergoing painful stimulation. PMID:17189238

  2. Anxiety Sensitivity and Pain-related Anxiety in the Prediction of Fear Responding to Bodily Sensations: A Laboratory Test

    PubMed Central

    Gonzalez, Adam; Zvolensky, Michael J.; Hogan, Julianna; McLeish, Alison C.; Weibust, Kristin S.

    2010-01-01

    Objective The present investigation sought to examine the simultaneous effects of anxiety sensitivity and pain-related anxiety on fear and anxious responding to a 10% carbon dioxide enriched air challenge. Methods Participants included 247 adults (53% women; age M = 21.91 years, SD = 8.41) recruited from the community. At the laboratory, participants were administered a structured clinical interview, completed a battery of self-report measures, and underwent a 10% carbon dioxide enriched air challenge. Results Both anxiety sensitivity and pain-related anxiety were significantly and uniquely predictive of post-challenge panic attacks, total post-challenge panic attack symptoms, and intensity of cognitive panic attack symptoms. Anxiety sensitivity, but not pain-related anxiety, also was predictive of post-challenge physical panic symptoms. The observed significant effects for both anxiety sensitivity and pain-related anxiety were evident above and beyond the variance accounted for by gender, age, current level of non-specific bodily pain, and negative affectivity. Neither anxiety sensitivity nor pain-related anxiety was significantly predictive of change in anxiety focused on bodily sensations or heart rate. Conclusion Results suggest that anxiety sensitivity and pain-related anxiety, although related to one another, may be independently important variables underlying fear reactivity to bodily sensations. PMID:21334497

  3. Nociceptor sensitization in pain pathogenesis

    PubMed Central

    Gold, Michael S; Gebhart, Gerald F

    2016-01-01

    The incidence of chronic pain is estimated to be 20–25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of the heterogeneity of mechanisms that contribute to the transition from acute tissue insult to chronic pain and to pain conditions for which the underlying pathology is not apparent. An intact central nervous system (CNS) is required for the conscious perception of pain, and changes in the CNS are clearly evident in chronic pain states. However, the blockage of nociceptive input into the CNS can effectively relieve or markedly attenuate discomfort and pain, revealing the importance of ongoing peripheral input to the maintenance of chronic pain. Accordingly, we focus here on nociceptors: their excitability, their heterogeneity and their role in initiating and maintaining pain. PMID:20948530

  4. Sleep and pain sensitivity in adults.

    PubMed

    Sivertsen, Børge; Lallukka, Tea; Petrie, Keith J; Steingrímsdóttir, Ólöf Anna; Stubhaug, Audun; Nielsen, Christopher Sivert

    2015-08-01

    Sleep problems and pain are major public health concerns, but the nature of the association between the 2 conditions is inadequately studied. The aim of this study was to determine whether a range of sleep measures is associated with experimental increased pain sensitivity. A cross-sectional large population-based study from 2007 to 2008, the Tromsø 6 study, provided data from 10,412 participants (age: mean [SD], 58 [13] years; 54% women). Self-reported sleep measures provided information on sleep duration, sleep onset latency (SOL), and sleep efficiency, as well as frequency and severity of insomnia. The main outcome measure was pain sensitivity tests, including assessment of cold-pressor pain tolerance. We found that all sleep parameters, except sleep duration, were significantly associated with reduced pain tolerance. Both the frequency and severity of insomnia, in addition to SOL and sleep efficiency, were associated with pain sensitivity in a dose-response manner. Adjusting for demographics and psychological distress reduced the strengths of the hazard ratios, but most associations remained significant in the fully adjusted models. There was also a synergistic interaction effect on pain tolerance when combining insomnia and chronic pain. We conclude that sleep problems significantly increase the risk for reduced pain tolerance. Because comorbid sleep problems and pain have been linked to elevated disability, the need to improve sleep among patients with chronic pain, and vice versa, should be an important agenda for future research. PMID:25915149

  5. Pain hypervigilance is associated with greater clinical pain severity and enhanced experimental pain sensitivity among adults with symptomatic knee osteoarthritis

    PubMed Central

    Herbert, Matthew S.; Goodin, Burel R.; Pero, Samuel T.; Schmidt, Jessica K.; Sotolongo, Adriana; Bulls, Hailey W.; Glover, Toni L.; King, Christopher D.; Sibille, Kimberly T.; Cruz-Almeida, Yenisel; Staud, Roland; Fessler, Barri J.; Bradley, Laurence A.; Fillingim, Roger B.

    2014-01-01

    Background Pain hypervigilance is an important aspect of the fear-avoidance model of pain that may help explain individual differences in pain sensitivity among persons with knee osteoarthritis (OA). Purpose The purpose of this study was to examine the contribution of pain hypervigilance to clinical pain severity and experimental pain sensitivity in persons with symptomatic knee OA. Methods We analyzed cross-sectional data from 168 adults with symptomatic knee OA. Quantitative sensory testing was used to measure sensitivity to heat pain, pressure pain, and cold pain, as well as temporal summation of heat pain, a marker of central sensitization. Results Pain hypervigilance was associated with greater clinical pain severity, as well as greater pressure pain. Pain hypervigilance was also a significant predictor of temporal summation of heat pain. Conclusions Pain hypervigilance may be an important contributor to pain reports and experimental pain sensitivity among persons with knee OA. PMID:24352850

  6. The effect of culture on pain sensitivity.

    PubMed

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

    2016-02-01

    Cross-cultural differences in pain sensitivity have been identified in pain-free subjects as well as in chronic pain patients. The aim was to assess the impact of culture on psychophysical measures using mechanical and electrical stimuli in patients with temporomandibular disorder (TMD) pain and pain-free matched controls in three cultures. This case-control study compared 122 female cases of chronic TMD pain (39 Saudis, 41 Swedes and 42 Italians) with equal numbers of age- and gender-matched TMD-free controls. Pressure pain threshold (PPT) and tolerance (PPTo) were measured over one hand and two masticatory muscles. Electrical perception threshold and electrical pain threshold (EPT) and tolerance (EPTo) were recorded between the thumb and index fingers. Italian females reported significantly lower PPT in the masseter muscle than other cultures (P < 0.001) and in the temporalis muscle than Saudis (P = 0.003). Swedes reported significantly higher PPT in the thenar muscle than other cultures (P = 0.017). Italians reported significantly lower PPTo in all muscles than Swedes (P ≤ 0.006) and in the masseter muscle than Saudis (P < 0.001). Italians reported significantly lower EPTo than other cultures (P = 0.01). Temporomandibular disorder cases, compared to TMD-free controls, reported lower PPT and PPTo in all the three muscles (P < 0.001). This study found cultural differences between groups in the PPT, PPTo and EPTo. Overall, Italian females reported the highest sensitivity to both mechanical and electrical stimulation, while Swedes reported the lowest sensitivity. Mechanical pain thresholds differed more across cultures than did electrical pain thresholds. Cultural factors may influence response to type of pain test. PMID:26371794

  7. 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…

  8. Pain Sensitivity and Recovery From Mild Chronic Sleep Loss

    PubMed Central

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

    2012-01-01

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

  9. 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. PMID:27152688

  10. 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. PMID:26262827

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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

  14. Modality and sex differences in pain sensitivity during human endotoxemia.

    PubMed

    Karshikoff, B; Lekander, M; Soop, A; Lindstedt, F; Ingvar, M; Kosek, E; Olgart Höglund, C; Axelsson, J

    2015-05-01

    Systemic inflammation can induce pain hypersensitivity in animal and human experimental models, and has been proposed to be central in clinical pain conditions. Women are overrepresented in many chronic pain conditions, but experimental studies on sex differences in pain regulation during systemic inflammation are still scarce. In two randomized and double blind placebo controlled experiments, we used low doses of lipopolysaccharide (LPS) as an experimental model of systemic inflammation. The first study employed 0.8ng/kg LPS in a within-subject design of 8 individuals (1 woman), and the second study 0.6ng/kg LPS in a between-subject design of 52 participants (29 women). We investigated the effect on (a) pressure, heat, and cold pain thresholds, (b) suprathreshold noxious heat and cold sensitivity, and (c) conditioned pain modulation (CPM), and differences between men and women. LPS induced significantly lower pressure pain thresholds as compared to placebo (mean change with the 0.8ng/kg dose being -64±30kPa P=.04; with the 0.6ng/kg dose -58±55kPa, P<.01, compared to before injection), whereas heat and cold pain thresholds remained unaffected (P's>.70). Suprathreshold noxious pain was not affected by LPS in men (P's⩾.15). However, LPS made women rated suprathreshold noxious heat stimuli as more painful (P=.01), and showed a tendency to rate noxious cold pain as more painful (P=.06) as compared to placebo. Furthermore, LPS impaired conditioned pain modulation, a measure of endogenous pain inhibition, but this effect was also restricted to women (P<.01, for men P=.27). Pain sensitivity correlated positively with plasma IL-6 and IL-8 levels. The results show that inflammation more strongly affects deep pain, rather than cutaneous pain, and suggest that women's pain perception and modulation is more sensitive to immune activation than men's. PMID:25486090

  15. Differential methylation of the TRPA1 promoter in pain sensitivity.

    PubMed

    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; 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

  16. 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

  17. Salivary Cortisol and Cold Pain Sensitivity in Female Twins

    PubMed Central

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

    2013-01-01

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

  18. Repression-sensitization, stress, and perception of pain in others.

    PubMed

    Von Baeyer, C

    1982-08-01

    To assess the influence of individuals' defensive style on perception of pain in others, 60 undergraduate women rated the amount of pain expressed in slides of people displaying high or low pain. Subjects were categorized as high or low on Byrne's Repression-Sensitization Scale, and their level of stress was varied by presentation of an anxiety-provoking film (stress condition) or a neutral film (control condition) prior to the rating task. A significant interaction between Repression-Sensitization and slide category (high versus low pain) indicated that sensitizers assigned higher ratings of pain than repressers to slides that were relatively low in rated expressiveness of pain. Individual differences in readiness to recognize potentially threatening stimuli seem most evident when the stimuli are relatively ambiguous. The manipulation of stress produced no significant effects on ratings of pain. PMID:7133920

  19. 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. PMID:21067864

  20. 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

  1. Are Indians and females less tolerant to pain? An observational study using a laboratory pain model.

    PubMed

    Das Gupta, E; Zailinawati, A H; Lim, A W; Chan, J B; Yap, S H; Hla, Y Y; Kamil, M A; Teng, C L

    2009-06-01

    In Malaysia, it is a common belief among health care workers that females and Indians have lower pain threshold. This experience, although based on anecdotal experience in the healthcare setting, does not allow differentiation between pain tolerance, and pain expression. To determine whether there is a difference in the tolerance to pain between the three main ethnic groups, namely the Malays, Chinese and Indians as well as between males and females. This was a prospective study, using a laboratory pain model (ischaemic pain tolerance) to determine the pain tolerance of 152 IMU medical students. The mean age of the students was 21.8 years (range 18-29 years). All of them were unmarried. The median of ischaemic pain tolerance for Malays, Chinese and Indians were 639s, 695s and 613s respectively (p = 0.779). However, statistically significant difference in ischaemic pain tolerance for males and females Indian students were observed. Possible ethnic difference in pain tolerance in casual observation is not verified by this laboratory pain model. Difference in pain tolerance between genders is shown only for Indians. PMID:20058568

  2. 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

  3. 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

  4. Elevated Pain Sensitivity in Chronic Pain Patients at Risk for Opioid Misuse

    PubMed Central

    Edwards, Robert R.; Wasan, Ajay D.; Michna, Ed; Greenbaum, Seth; Ross, Ed; Jamison, Robert N.

    2011-01-01

    This study employed quantitative sensory testing (QST) to evaluate pain responses in chronic spinal pain patients at low risk and high risk for opioid misuse, with risk classification based on scores on the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Patients were further sub-grouped according to current use of prescription opioids. Of the 276 chronic pain patients tested, approximately 65% were taking opioids; a median split was used to further categorize these patients as being on lower or higher doses of opioids. The highrisk group (n= 161) reported higher levels of clinical pain, had lower pressure and thermal pain thresholds at multiple body sites, had lower heat pain tolerance, and rated repetitive mechanical stimuli as more painful relative to the low-risk group (n= 115; p’s< .01). In contrast, QST measures did not differ across opioid groups. Multiple linear regression analysis suggested that indices of pain-related distress (i.e., anxiety and catastrophizing about pain) were also predictive of hyperalgesia, particularly in patients taking opioids. Collectively, regardless of opioid status, the high-risk group was hyperalgesic relative to the low-risk group; future opioid treatment studies may benefit from the classification of opioid risk, and the examination of pain sensitivity and other factors that differentiate high- and low-risk groups. PMID:21680252

  5. 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

  6. Pain sensitivity and opioid analgesia: a pharmacogenomic twin study.

    PubMed

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

    2012-07-01

    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 μ-opioid 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

  7. Pain sensitivity following loss of cholinergic basal forebrain (CBF) neurons in the rat.

    PubMed

    Vierck, C J; Yezierski, R P; Wiley, R G

    2016-04-01

    Flexion/withdrawal reflexes are attenuated by spinal, intracerebroventricular (ICV) and systemic delivery of cholinergic agonists. In contrast, some affective reactions to pain are suppressed by systemic cholinergic antagonism. Attention to aversive stimulation can be impaired, as is classical conditioning of fear and anxiety to aversive stimuli and psychological activation of stress reactions that exacerbate pain. Thus, in contrast to the suppressive effects of cholinergic agonism on reflexes, pain sensitivity and affective reactions to pain could be attenuated by reduced cerebral cholinergic activation. This possibility was evaluated in the present study, using an operant test of escape from nociceptive thermal stimulation (10 °C and 44.5 °C) before and after destruction of basal forebrain cholinergic neurons. ICV injection of 192 IgG-saporin produced widespread loss of basal forebrain cholinergic innervation of the cerebral cortex and hippocampus. Post-injection, escape from thermal stimulation was decreased with no indication of recovery for upto 19 weeks. Also, the normal hyperalgesic effect of sound stress was absent after ICV 192-sap. Effects of cerebral cholinergic denervation or stress on nociceptive licking and guarding reflexes were not consistent with the effects on operant escape, highlighting the importance of evaluating pain sensitivity of laboratory animals with an operant behavioral test. These results reveal that basal forebrain cholinergic transmission participates in the cerebral processing of pain, which may be relevant to the pain sensitivity of patients with Alzheimer's disease who have prominent degeneration of basal forebrain cholinergic neurons. PMID:26812034

  8. 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

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

    PubMed Central

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

    2014-01-01

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

  10. 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. PMID:26021808

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

    PubMed

    Dowman, Robert

    2014-06-01

    Pain typically signals damage to the body, and as such can be perceived as threatening and can elicit a strong emotional response. This ecological significance undoubtedly underlies pain's well-known ability to demand attention. However, the neural mechanisms underlying this ability are poorly understood. Previous work from the author's laboratory has reported behavioral evidence suggesting that participants disengage their attention from an incorrectly cued visual target stimulus and reorient it toward a somatic target more rapidly when the somatic target is painful than when it is nonpainful. Furthermore, electrophysiological data suggest that this effect is mediated by a stimulus-driven process, in which somatic threat detectors located in the dorsal posterior insula activate the medial and lateral prefrontal cortex areas involved in reorienting attention toward the painful target. In these previous studies, the painful and nonpainful somatic targets were given in separate experiments involving different participants. Here, the nonpainful and painful somatic targets were presented in random order within the same block of trials. Unlike in the previous studies, both the nonpainful and painful somatic targets activated the somatic threat detectors, and the times taken to disengage and reorient attention were the same for both. These electrophysiological and behavioral data suggest that somatic threat detectors can become sensitized to nonpainful somatic stimuli that are presented in a context that includes painful stimuli. PMID:24366657

  12. Integrative Approach to Pain Genetics Identifies Pain Sensitivity Loci across Diseases

    PubMed Central

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

    2012-01-01

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

  13. 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

  14. 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

  15. 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

  16. 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. PMID:21291919

  17. Xenon-induced changes in CNS sensitization to pain.

    PubMed

    Adolph, Oliver; Köster, Sarah; Georgieff, Michael; Bäder, Stefan; Föhr, Karl J; Kammer, Thomas; Herrnberger, Bärbel; Grön, Georg

    2010-01-01

    Electrophysiological investigations of the spinal cord in animals have shown that pain sensitizes the central nervous system via glutamate receptor dependent long-term potentiation (LTP) related to an enhancement of pain perception. To expand these findings, we used functional magnetic resonance (fMRI), blood oxygen level dependent (BOLD) and perfusion imaging in combination with repeated electrical stimulation in humans. Specifically we monitored modulation of somatosensory processing during inhibition of excitatory transmission by ocular application of the glutamate receptor antagonist xenon. BOLD responses upon secondary stimulation increased in mid insular and in primary/secondary sensory cortices under placebo and decreased under xenon treatments. Xenon-induced decreases in regional perfusion were confined to stimulation responsive brain regions and correlated with time courses of xenon concentrations in the cranial blood. Moreover, effects of xenon on behavioral, fMRI and perfusion data scaled with stimulus intensity. The dependence of pain sensitization on sufficient pre-activation reflects a multistage process which is characteristic for glutamate receptor related processes of LTP. This study demonstrates how LTP related processes known from the cellular level can be investigated at the brain systems level. PMID:19703572

  18. Mechanical pain sensitivity and the severity of chronic neck pain and disability are not modulated across the menstrual cycle

    PubMed Central

    Balter, JE; Molner, JL; Kohrt, WM; Maluf, KS

    2013-01-01

    Despite the high prevalence of neck pain among women, menstrual effects on regional pain outcomes have not been investigated in this clinical population. This study evaluated menstrual effects on mechanical pain sensitivity (Pressure Pain Threshold; PPT), neck pain intensity (Numeric Pain Rating Scale; NPRS) and neck-related disability (Neck Disability Index; NDI) in 22 normally menstruating (NM) and 17 hormonal contraceptive (HC) users with chronic neck pain. Sex hormones, PPT, and NDI were measured during the early follicular (F1), late follicular (F2), and luteal (L) menstrual phases. Daily NPRS scores were recorded in an online symptom diary and averaged within each phase. Estradiol and progesterone increased only for NM women in F2 and L, respectively. Phase effects on PPT (η2=0.003), NDI (η2=0.003), and NPRS (η2=0.016) for NM women were small, and did not differ from the HC group (p≥0.386). Averaged across the menstrual cycle, PPT scores explained 29% of the variance in NPRS scores for NM women, but were not associated with NDI scores in either group. Results indicate that that magnitude of menstrual effects on mechanical pain sensitivity, and the severity of neck pain and disability do not exceed thresholds of clinically detectable change in women with chronic neck pain. PERSPECTIVE Fluctuations in evoked and clinical pain outcomes across the menstrual cycle do not appear to be of sufficient magnitude to impact clinical decision-making for women with chronic neck pain. PMID:24021578

  19. The dynamics of pain: Evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain

    PubMed Central

    Jepma, Marieke; Jones, Matt; Wager, Tor D.

    2014-01-01

    Repeated exposure to noxious stimuli changes their painfulness, due to multiple adaptive processes in the peripheral and central nervous system. Somewhat paradoxically, repeated stimulation can produce an increase (sensitization) or a decrease (habituation) in pain. Adaptation processes may also be body-site-specific or operate across body sites, and considering this distinction may help explain the conditions under which habituation vs. sensitization occurs. To dissociate the effects of site-specific and site-nonspecific adaptation processes, we examined reported pain in 100 participants during counterbalanced sequences of noxious thermal stimulation on multiple skin sites. Analysis of pain ratings revealed two opposing sequential effects: repeated stimulations of the same skin site produced temperature-dependent habituation, whereas repeated stimulations across different sites produced sensitization. Stimulation trials were separated by ~20 seconds and sensitization was unrelated to the distance between successively stimulated sites, suggesting that neither temporal nor spatial summation occurred. To explain these effects, we propose a dynamic model with two adaptation processes, one site-specific and one site-nonspecific. The model explains 93% of the variance in the group-mean pain ratings after controlling for current stimulation temperature, with its estimated parameters showing evidence for habituation for the site-specific process and sensitization for the site-nonspecific process. The two pain-adaptation processes revealed in this study, and the ability to disentangle them, may hold keys to understanding multiple pain-regulatory mechanisms and their disturbance in chronic-pain syndromes. Perspective This article presents novel evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain, which can be disentangled (and the direction and strength of each process estimated) by a dynamic model. The dissociation of site

  20. 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. PMID:23563122

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

    PubMed

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

    2015-10-01

    Pain is common in patients after orthopedic surgery. The 11-face Faces Pain Scale has not been validated for use in adult patients with postoperative pain. To assess the validity of the 11-face Faces Pain Scale and its ability to detect responses to pain medications, and to determine whether the sensitivity of the 11-face Faces Pain Scale for detecting changes in pain intensity over time is associated with gender differences in adult postorthopedic surgery patients. The 11-face Faces Pain Scale was translated into Vietnamese using forward and back translation. Postoperative pain was assessed using an 11-point numerical rating scale and the 11-face Faces Pain Scale on the day of surgery, and before (Time 1) and every 30 minutes after (Times 2-5) the patients had taken pain medications on the first postoperative day. The 11-face Faces Pain Scale highly correlated with the numerical rating scale (r = 0.78, p < .001). When the scores from each follow-up test (Times 2-5) were compared with those from the baseline test (Time 1), the effect sizes were -0.70, -1.05, -1.20, and -1.31, and the standardized response means were -1.17, -1.59, -1.66, and -1.82, respectively. The mean change in pain intensity, but not gender-time interaction effect, over the five time points was significant (F = 182.03, p < .001). Our results support that the 11-face Faces Pain Scale is appropriate for measuring acute postoperative pain in adults. PMID:25962544

  2. Assessment of Functional and Behavioral Changes Sensitive to Painful Disc Degeneration

    PubMed Central

    Lai, Alon; Moon, Andrew; Purmessur, Devina; Skovrlj, Branko; Winkelstein, Beth A.; Cho, Samuel K.; Hecht, Andrew C.; Iatridis, James C.

    2015-01-01

    The development of an in vivo rodent discogenic pain model can provide insight into mechanisms for painful disc degeneration. Painful disc degeneration in rodents can be inferred by examining responses to external stimuli, observing pain-related behaviors, and measuring functional performance. This study compared the sensitivity of multiple pain and functional assessment methods to disc disruption for identifying the parameters sensitive to painful disc degeneration in rats. Disc degeneration was induced in rats by annular injury with saline injection. The severity of disc degeneration, pain sensitivity, and functional performance were compared to sham and näve control rats. Saline injection induced disc degeneration with decreased disc height and MRI signal intensity as well as more fibrous nucleus pulposus, disorganized annular lamellae and decreased proteoglycan. Rats also demonstrated increased painful behaviors including decreased hindpaw mechanical and thermal sensitivities, increased grooming, and altered gait patterns with hindpaw mechanical hyperalgesia and duration of grooming tests being most sensitive. This is the first study to compare sensitivities of different pain assessment methods in an in vivo rat model of disc degeneration. Hindpaw mechanical sensitivity and duration of grooming were the most sensitive parameters to surgically induced degenerative changes and overall results were suggestive of disc degeneration associated pain. PMID:25731955

  3. Beyond PAINs: Chemotype Sensitivity of Protein Methyltransferases in Screens.

    PubMed

    Gao, Cen; Margolis, Brandon J; Strelow, John M; Vidler, Lewis R; Mader, Mary M

    2016-02-11

    Screening of the relatively new target class, the lysine and arginine methyltransferases (MTases), presents unique challenges in the identification and confirmation of active chemical matter. Examination of high throughput screening data generated using Scintillation Proximity Assay (SPA) format for a number of protein MTase targets reveals sensitivity to both the known pan assay interference compounds (PAINS) and also other scaffolds not currently precedented as assay interferers. We find that, in general, true actives show significant selectivity within the MTase family. With the exception of slight modifications of SAM-like compounds, scaffolds that are observed frequently in multiple MTase assays should be viewed with caution and should be carefully validated before following up. PMID:26985291

  4. 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. PMID:26963852

  5. 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

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

    PubMed

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

    2016-01-01

    The aim of this study was to investigate the hypothesis that chronic widespread pain, (CWP) drawn by patients on a body diagram, could be used as a screening tool for increased pain sensitization, psycho-social load, and utilization of pain management strategies. The triage questionnaires of 144 adults attending a chronic pain outpatients' clinic were audited and the percentage pain surface area (PPSA) drawn on their body diagrams was calculated using the "rule of nines" (RON) method for burns area assessment. Outcomes were measured using the painDETECT Questionnaire (PD-Q) and other indices and compared using a nonrandomized, case-control method. It was found that significantly more subjects with CWP (defined as a PPSA ≥ 20%) reported high (≥ 19) PD-Q scores (suggesting pain "sensitization" or neuropathic pain) (P = 0.0002), "severe" or "extremely severe" anxiety scores on the Depression, Anxiety and Stress Scale-21 Items Questionnaire (P = 0.0270), ≥ 5 psycho-social stressors (P = 0.0022), ≥ 5 significant life events (P = 0.0098), and used ≥ 7 pain management strategies (PMS) (P < 00001), compared to control subjects with a lower PPSA. A Widespread Pain Index score ≥ 7 (OR = 11.36), PD-Q score ≥ 19 (OR = 4.46) and use of ≥ 7 PMS (OR = 5.49) were independently associated with CWP. This study demonstrates that calculating PPSA on a body diagram (using the RON method) is a valid and convenient "snapshot" screening tool to identify patients with an increased likelihood of pain sensitization, psycho-social load, and utilizing pain management resources. PMID:25469881

  7. Assessment of musculoskeletal pain sensitivity and temporal summation by cuff pressure algometry: a reliability study.

    PubMed

    Graven-Nielsen, Thomas; Vaegter, Henrik Bjarke; Finocchietti, Sara; Handberg, Gitte; Arendt-Nielsen, Lars

    2015-11-01

    Chronic musculoskeletal pain is linked with sensitization, and standardized methods for assessment are needed. This study investigated (1) the test-retest reliability of computer-controlled cuff-pressure algometry (pain thresholds and temporal pain summation) on the arm and leg and (2) conditioned pain modulation (CPM) assessed by cuff algometry. The influences of age and gender were evaluated. On 2 different days, cuff pain threshold (cPPT), cuff pain tolerance (cPTT), and temporal summation of pain (TSP) by visual analog scale scores to 10 repeated cuff stimulations at cPTT intensity, as well as pressure pain threshold with handheld pressure algometry, were assessed in 136 healthy subjects. In one session, cuff pain sensitivity was also assessed before and after cold pressor-induced CPM. Good-to-excellent intraclass correlations (0.60-0.90) were demonstrated for manual and cuff algometry, and no systematic bias between sessions was found for cPPT, cPTT, and TSP on the leg and for cPTT and TSP on the arm. Cuff pressure pain threshold and cPTT were higher in men compared with women (P < 0.05). Middle-aged subjects had higher pressure pain threshold, but lower cPPT and cPTT, compared with younger subjects (P < 0.05). Temporal summation of pain was increased in women compared with men (P < 0.05). Cuff algometry was sensitive to CPM demonstrated as increased cPPT and cPTT and reduced TSP (P < 0.05). Reliability and sensitivity of computer-controlled cuff algometry for pain assessment is comparable with manual pressure algometry and constitutes a user-independent method for assessment of pain. Difference in age-related pain sensitivity between manual and cuff algometry should be further investigated. PMID:26172551

  8. Use of the painDETECT tool in rheumatoid arthritis suggests neuropathic and sensitization components in pain reporting

    PubMed Central

    Ahmed, Saqa; Magan, Tejal; Vargas, Mario; Harrison, Abiola; Sofat, Nidhi

    2014-01-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune condition typified by systemic inflammation targeted toward synovial joints. Inhibition of proinflammatory networks by disease-modifying antirheumatic drugs, eg, methotrexate and biologic therapies, including tumor necrosis factor-α inhibitors, often leads to suppression of disease activity observed at the clinical level. However, despite the era of widespread use of disease-modifying treatments, there remain significant groups of patients who continue to experience pain. Our study formulated a pain assessment tool in the arthritis clinic to assess feasibility of measurements including the visual analog scale (VAS) and painDETECT to assess multimodal features of pain in people with established RA (n=100). Clinical measures of disease activity (Disease Activity Score in 28 Joints [DAS28]) were also recorded. Our data showed that despite the majority of subjects on at least one disease-modifying agent, the majority of patients reported severe pain (54%) by VAS, despite well-controlled clinical disease, with mean DAS28 2.07±0.9. Using the painDETECT questionnaire, 67% of patients had unlikely neuropathic pain. A significant proportion of subjects (28%) had possible neuropathic pain and 5% had features of likely neuropathic pain by painDETECT scoring. We found a positive correlation between VAS and painDETECT (R2=0.757). Of note, the group who had likely or probable neuropathic pain also showed significantly increased pain reporting by VAS (P<0.01). Subjects who were clinically obese (body mass index >30) also had statistically higher proportions of pain reporting (VAS 89.0±0.7 mm) compared with subjects who had a normal body mass index (VAS 45.2±21.8 mm), P<0.05. Our findings suggest that multimodal features of pain perception exist in RA, including neuropathic and sensitization elements, perhaps explaining why a subgroup of people with RA continue to experience ongoing pain, despite their apparent

  9. A meta-analysis on pain sensitivity in self-injury.

    PubMed

    Koenig, J; Thayer, J F; Kaess, M

    2016-06-01

    Individuals engaging in self-injurious behavior (SIB) frequently report absence of pain during acts of SIB. While altered pain sensitivity is discussed as a risk factor for the engagement in SIB, results have been mixed with considerable variance across reported effect sizes, in particular with respect to the effect of co-morbid psychopathology. The present meta-analysis aimed to summarize the current evidence on pain sensitivity in individuals engaging in SIB and to identify covariates of altered pain processing. Three databases were searched without restrictions. Additionally a hand search was performed and reference lists of included studies were checked for potential studies eligible for inclusion. Thirty-two studies were identified after screening 720 abstracts by two independent reviewers. Studies were included if they reported (i) an empirical investigation, in (ii) humans, including a sample of individuals engaging in (iii) SIB and a group of (iv) healthy controls, (v) receiving painful stimulation. Random-effects meta-analysis was performed on three pain-related outcomes (pain threshold, pain tolerance, pain intensity) and several population- and study-level covariates (i.e. age, sex, clinical etiology) were subjected to meta-regression. Meta-analysis revealed significant main effects associated with medium to large effect sizes for all included outcomes. Individuals engaging in SIB show greater pain threshold and tolerance and report less pain intensity compared to healthy controls. Clinical etiology and age are significant covariates of pain sensitivity in individuals engaging in SIB, such that pain threshold is further increased in borderline personality disorder compared to non-suicidal self-injury. Mechanisms underlying altered pain sensitivity are discussed. PMID:26964517

  10. 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

  11. Catastrophizing and anxiety sensitivity mediate the relationship between persistent pain and emotional eating.

    PubMed

    Janke, E Amy; Jones, Elizabeth; Hopkins, Christina M; Ruggieri, Madelyn; Hruska, Alesha

    2016-08-01

    Stress-induced or "emotional eating" contributes to increased caloric intake and weight gain, yet models examining psychosocial factors that promote and sustain this behavior are incomplete. There is a need to identify explicit, clinically-relevant mechanisms of emotional eating behavior. Pain is a common stressor associated with increased weight and, potentially, altered eating behaviors. The present study applies the Fear Avoidance Model (FAM) of pain to examine processes that may explain the relationship between pain and increased weight while also providing the opportunity to examine specific mechanisms that may encourage eating during a variety of stressors. Our aim is to better understand the impact of pain on eating behavior and the potential for the FAM to improve our understanding of the psychological mechanisms that promote eating during times of duress. A survey of 312 adults explored the link between pain experience and stress-induced eating, further examining the mediating effects of the psychological aspects of the FAM (e.g., anxiety sensitivity, catastrophizing, and pain-related fear). 24% of respondents reported persistent pain, and had significantly higher BMIs than their pain-free peers. All three FAM components were positively correlated with measures of emotional, external, and restrained eating. Anxiety sensitivity and catastrophizing significantly mediated the relationship between persistent pain and emotional eating behavior, while anxiety sensitivity alone mediated the relationship between persistent pain and external eating. Findings suggest pain may be associated with increased likelihood for emotional eating and that characteristics from FAM, in particular anxiety sensitivity and catastrophizing, may mediate the relationship between the presence of persistent pain and emotional eating behavior. Evidence-based treatments targeting anxiety sensitivity and catastrophizing could be useful to address emotional eating in individuals struggling

  12. 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

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

    PubMed Central

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

    2014-01-01

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

  14. Sequelae of prenatal serotonin depletion and stress on pain sensitivity in rats.

    PubMed

    Butkevich, I P; Mikhailenko, V A; Leont'eva, M N

    2005-11-01

    The effects of interrupted synthesis of serotonin (5-HT) and immobilization stress applied to pregnant Wistar rats on behavioral measures of pain sensitivity in the formalin test were studied in their offspring at age 90 days. Prenatal 5-HT depletion decreased pain sensitivity in one third of rats and produced no significant change in the remainder. However, the latter showed a clear tendency to an increase in the interphase interval in females and a decrease in males. Prenatal stress increased pain sensitivity in 50% of rats with prenatal 5-HT deficiency and decreased pain sensitivity in the remainder. Increases in pain sensitivity were also seen in control rats (with prenatal injections of physiological saline), though to a significantly lesser extent than in animals with prenatal 5-HT depletion. The latter showed gender differences in the effects of prenatal stress on pain sensitivity. The present data provide evidence that prenatal 5-HT depletion has long-term effects on the functional activity of the nociceptive system and the important role of 5-HT in mediating the effects of prenatal stress on pain sensitivity in the formalin test. PMID:16270174

  15. 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. PMID:24223836

  16. The Effect of Pressure Pain Sensitivity and Patient Factors on Self-Reported Pain-Disability in Patients with Chronic Neck Pain

    PubMed Central

    Uddin, Zakir; MacDermid, Joy C.; Woodhouse, Linda J.; Triano, John J.; Galea, Victoria; Gross, Anita R.

    2014-01-01

    The study was conducted to estimate the extent to which pressure pain sensitivity (PPS) and patient factors predict pain-related disability in patients with neck pain (NP), and to determine if PPS differs by gender. Forty-four participants with a moderate level of chronic NP were recruited for this cross sectional study. All participants were asked to complete self-reported assessments of pain, disability and comorbidity and then underwent PPS testing at 4-selected body locations. Pearson`s r w was computed to explore relationships between the PPS measures and the self-reported assessments. Regression models were built to identify predictors of pain and disability. An independent sample t-test was done to identify gender-related differences in PPS, pain-disability and comorbidity. In this study, greater PPS (threshold and tolerance) was significantly correlated to lower pain-disability (r = -.30 to -.53, p≤0.05). Age was not correlated with pain or disability but comorbidity was (r= 0.42-.43, p≤0.01). PPS at the 4-selected body locations was able to explain neck disability (R2=25-28%). Comorbidity was the strongest predictor of neck disability (R2 =30%) and pain (R2=25%). Significant mean differences for gender were found in PPS, disability and comorbidity, but not in pain intensity or rating. This study suggests that PPS may play a role in outcome measures of pain and disability but between-subject comparisons should consider gender and comorbidity issues. PMID:25320651

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

    PubMed Central

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

    2012-01-01

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

  18. Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

    PubMed Central

    Latremoliere, Alban; Woolf, Clifford J.

    2009-01-01

    Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. Perspective In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors. PMID:19712899

  19. MicroRNAs downregulated in neuropathic pain regulate MeCP2 and BDNF related to pain sensitivity.

    PubMed

    Manners, Melissa T; Tian, Yuzhen; Zhou, Zhaolan; Ajit, Seena K

    2015-01-01

    Nerve injury induces chronic pain and dysregulation of microRNAs in dorsal root ganglia (DRG). Several downregulated microRNAs are predicted to target Mecp2. MECP2 mutations cause Rett syndrome and these patients report decreased pain perception. We confirmed MeCP2 upregulation in DRG following nerve injury and repression of MeCP2 by miRNAs in vitro. MeCP2 regulates brain-derived neurotrophic factor (BDNF) and downregulation of MeCP2 by microRNAs decreased Bdnf in vitro. MeCP2 T158A mice exhibited reduced mechanical sensitivity and Mecp2-null and MeCP2 T158A mice have decreased Bdnf in DRG. MeCP2-mediated regulation of Bdnf in the DRG could contribute to altered pain sensitivity. PMID:26448907

  20. Composite Pain Index (CPI): Reliability, Validity, and Sensitivity of a Patient-Reported Outcome for Research

    PubMed Central

    Wilkie, Diana J.; Molokie, Robert E.; Suarez, Marie L.; Ezenwa, Miriam O.; Wang, Zaijie J.

    2015-01-01

    Objective A single score that represents the multidimensionality of pain would be an innovation for patient-reported outcomes. Our aim was to determine the reliability, validity, and sensitivity of the Composite Pain Index. Design Methodological analysis of data from a randomized controlled, pretest/posttest education-based intervention study. Setting The study was conducted in outpatient oncology clinics. Subjects The 176 subjects had pain, were 52 ± 12.5 years on average, 63% were female, and 46% had stage IV cancers. Methods We generated the Composite Pain Index from pain location, intensity, quality, and pattern scores measured with an electronic version of Melzack’s McGill Pain Questionnaire. Results The internal consistency values for the individual scores comprising the Composite Pain Index were adequate (.71 baseline, .69 posttest). Principal components analysis extracted one factor with an eigenvalue of 2.17 with explained variance of 54% at baseline and replicated the one factor with an eigenvalue of 2.11 at posttest. The factor loadings for location, intensity, quality, and pattern were .65, .71, .85, and .71 respectively (baseline) and .59, .81, .84, and .63 respectively (posttest). The Composite Pain Index was sensitive to an education intervention effect. Conclusions Findings support the Composite Pain Index as a score that integrates the multidimensional pain experience in people with cancer. It could be used as a patient-reported outcome measure to quantify the complexity of pain in clinical research and population studies of cancer pain and studied for relevance in other pain populations. PMID:25712169

  1. 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

  2. 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

  3. 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. PMID:26058036

  4. Pain

    MedlinePlus

    ... realize you have a medical problem that needs treatment. Once you take care of the problem, pain ... Fortunately, there are many ways to treat pain. Treatment varies depending on the cause of pain. Pain ...

  5. 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. PMID:25054394

  6. Reduction of Pain Sensitivity After Somatosensory Therapy in Adults with Cerebral Palsy

    PubMed Central

    Riquelme, Inmaculada; Zamorano, Anna; Montoya, Pedro

    2013-01-01

    Objective: Pain and deficits in somatosensory processing seem to play a relevant role in cerebral palsy (CP). Rehabilitation techniques based on neuroplasticity mechanisms may induce powerful changes in the organization of the primary somatosensory cortex and have been proved to reduce levels of pain and discomfort in neurological pathologies. However, little is known about the efficacy of such interventions for pain sensitivity in CP individuals. Methods: Adults with CP participated in the study and were randomly assigned to the intervention (n = 17) or the control group (n = 20). The intervention group received a somatosensory therapy including four types of exercises (touch, proprioception, vibration, and stereognosis). All participants were asked to continue their standardized motor therapy during the study period. Several somatosensory (pain and touch thresholds, stereognosis, proprioception, texture recognition) and motor parameters (fine motor skills) were assessed before, immediately after and 3 months after the therapy (follow-up). Results: Participants of the intervention group showed a significant reduction on pain sensitivity after treatment and at follow-up after 3 months, whereas participants in the control group displayed increasing pain sensitivity over time. No improvements were found on touch sensitivity, proprioception, texture recognition, or fine motor skills. Conclusion: Data suggest the possibility that somatosensory therapy was effective in eliciting changes in central somatosensory processing. This hypothesis may have implications for future neuromodulatory treatment of pain complaints in children and adults with CP. PMID:23805086

  7. Interhemispheric Dorsolateral Prefrontal Cortex Connectivity is Associated with Individual Differences in Pain Sensitivity in Healthy Controls.

    PubMed

    Sevel, Landrew S; Letzen, Janelle E; Staud, Roland; Robinson, Michael E

    2016-06-01

    The dorsolateral prefrontal cortex (DLPFC) is implicated in pain modulation through multiple psychological processes. Recent noninvasive brain stimulation studies suggest that interhemispheric DLPFC connectivity influences pain tolerance and discomfort by altering interhemispheric inhibition. The structure and role of interhemispheric DLPFC connectivity in pain processing have not been investigated. The present study used dynamic causal modeling (DCM) for fMRI to investigate transcallosal DLPFC connectivity during painful stimulation in healthy volunteers. DCM parameters were used to predict individual differences in sensitivity to noxious heat stimuli. Bayesian model selection results indicated that influences among the right DLPFC (rDLPFC) and left DLPFC (lDLPFC) are modulated during painful stimuli. Regression analyses revealed that greater rDLPFC→lDLPFC couplings were associated with higher suprathreshold pain temperatures. These results highlight the role of interhemispheric connectivity in pain modulation and support the preferential role of the right hemisphere in pain processing. Knowledge of these mechanisms may improve understanding of abnormal pain modulation in chronic pain populations. PMID:26916416

  8. Thrombospondin-4 and excitatory synaptogenesis promote spinal sensitization after painful mechanical joint injury.

    PubMed

    Crosby, Nathan D; Zaucke, Frank; Kras, Jeffrey V; Dong, Ling; Luo, Z David; Winkelstein, Beth A

    2015-02-01

    Facet joint injury induces persistent pain that may be maintained by structural plasticity in the spinal cord. Astrocyte-derived thrombospondins, especially thrombospondin-4 (TSP4), have been implicated in synaptogenesis and spinal sensitization in neuropathic pain, but the TSP4 response and its relationship to synaptic changes in the spinal cord have not been investigated for painful joint injury. This study investigates the role of TSP4 in the development and maintenance of persistent pain following injurious facet joint distraction in rats and tests the hypothesis that excitatory synaptogenesis contributes to such pain. Painful facet joint loading induces dorsal horn excitatory synaptogenesis along with decreased TSP4 in the DRG and increased astrocytic release of TSP4 in the spinal cord, all of which parallel the time course of sustained tactile allodynia. Blocking injury-induced spinal TSP4 expression with antisense oligonucleotides or reducing TSP4 activity at its neuronal receptor in the spinal cord with gabapentin treatment both attenuate the allodynia and dorsal horn synaptogenesis that develop after painful facet joint loading. Increased spinal TSP4 also facilitates the development of allodynia and spinal hyperexcitability, even after non-painful physiological loading of the facet joint. These results suggest that spinal TSP4 plays an important role in the development and maintenance of persistent joint-mediated pain by inducing excitatory synaptogenesis and facilitating the transduction of mechanical loading of the facet joint that leads to spinal hyperexcitability. PMID:25483397

  9. The evolution of the painful sensitivity in acute and chronic stress.

    PubMed

    Cristea, A; Ciobanu, A; Stoenescu, M; Rusei, I

    1994-01-01

    The clinical research was made on two groups of young volunteer students. We considered stress consisting in chronic informational overexposure during the examination session and the acute stress from their emotions before a hard examination. The painful sensitivity was analysed by measuring the retraction time of the finger from water at 55 degrees C. The experimental research was made on a group of 100 male mice. The acute stress was performed by subjecting each mouse to swim (behavioral despair test). Painful sensitivity was determined by the test of the hot plate heated at 50 degrees C. Individuals with hyper (H) and hypo (h) painful sensitivity were selected for the tests. In chronic stress, the results proved increased painful sensitivity (hyperalgia) more important at "h" compared to "H" (p < 0.05). In acute stress decreased painful sensitivity (stress analgesia) was noticed more significant at "H" compared to h" (p < 0.05). All these results suggested that the extreme "H" and "h" are two different stress behaviors with opposite mechanisms involved in stress analgesia. This hypothesis is related with studies which demonstrate the involvement in stress analgesia of non-opioid monoaminergic mechanisms together with the opioid mechanisms (Lewis, 1980). PMID:8640371

  10. [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. PMID:26701631

  11. [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. PMID:26571803

  12. 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

  13. Age and race effects on pain sensitivity and modulation among middle-aged and older adults

    PubMed Central

    Riley, Joseph L.; Cruz-Almeida, Yenisel; Glover, Toni L.; King, Christopher D.; Goodin, Burel R.; Sibille, Kimberly T.; Bartley, Emily J.; Herbert, Matthew S.; Sotolongo, Adriana; Fessler, Barri J.; Redden, David T.; Staud, Roland; Bradley, Laurence A.; Fillingim, Roger B

    2014-01-01

    This study tested the effects of aging and race on responses to noxious stimuli using a wide range of stimulus modalities. The participants were 53 non-Hispanic Blacks and 138 non-Hispanic White adults, ages 45 to 76. The participants completed a single 3-hour sensory testing session where responses to thermal, mechanical, and cold stimuli were assessed. The results suggest that there are selected age differences, with the older group less sensitive to warm and painful heat stimuli than middle-aged participants, particularly at the knee. This site effect supports the hypothesis that the greatest decrement in pain sensitivity associated with aging occurs in the lower extremities. In addition, there were several instances where age and race effects were compounded, resulting in greater race differences in pain sensitivity among the older participants. Overall, the data suggest that previously reported race differences in pain sensitivity emerged in our older samples, and this study contributes new findings in that these differences may increase with age in non-Hispanic Blacks for temporal summation and both heat and cold immersion tolerance. We have added to the aging and pain literature by reporting several small to moderate differences in responses to heat stimuli between middle and older age adults. PMID:24239561

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Association between genetic polymorphisms of the β1-adrenergic receptor and sensitivity to pain and fentanyl in patients undergoing painful cosmetic surgery.

    PubMed

    Moriyama, Ayako; Nishizawa, Daisuke; Kasai, Shinya; Hasegawa, Junko; Fukuda, Ken-ichi; Nagashima, Makoto; Katoh, Ryoji; Ikeda, Kazutaka

    2013-01-01

    Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, can hamper effective pain treatment. The adrenergic system is reportedly involved in the mechanisms of pain and analgesia. Here, we focused on one of the adrenergic receptor genes, ADRB1, and analyzed the influence of single-nucleotide polymorphisms (SNPs) in the ADRB1 gene on individual differences in pain and analgesic sensitivity. We examined associations between pain and fentanyl sensitivity and the two SNPs, A145G and G1165C, in the human ADRB1 gene in 216 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. The patients who carried the A-allele of the A145G SNP were more sensitive to cold pressor- induced pain than those who did not carry this allele, especially in male patients. The analgesic effect was significantly less in females who carried the G-allele of the G1165C SNP than the females who did not carry the G-allele. The haplotype analysis revealed a significant decrease in 24-h postoperative fentanyl use in female 145A/1165C haplotype carriers. These results suggest that SNPs in the ADRB1 gene are associated with individual differences in pain and analgesic sensitivity, and analyzing these SNPs may promote personalized pain treatment in the future. PMID:23257656

  19. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization.

    PubMed

    Ford, Anthony P

    2012-02-01

    Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers

  20. 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. PMID:26004314

  1. 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

  2. The Associations between Pain Sensitivity and Knee Muscle Strength in Healthy Volunteers: A Cross-Sectional Study

    PubMed Central

    Graven-Nielsen, Thomas; Bliddal, Henning

    2013-01-01

    Objectives. To investigate associations between muscle strength and pain sensitivity among healthy volunteers and associations between different pain sensitivity measures. Methods. Twenty-eight healthy volunteers (21 females) participated. Pressure pain thresholds (PPTs) were obtained from 1) computer-controlled pressure algometry on the vastus lateralis and deltoid muscles and on the infrapatellar fat pad and 2) computerized cuff pressure algometry applied on the lower leg. Deep-tissue pain sensitivity (intensity and duration) was assessed by hypertonic saline injections into the vastus lateralis, deltoid, and infrapatellar fat pad. Quadriceps and hamstring muscle strength was assessed isometrically at 60-degree knee flexion using a dynamometer. Associations between pain sensitivity and muscle strength were investigated using multiple regressions including age, gender, and body mass index as covariates. Results. Knee extension strength was associated with computer-controlled PPT on the vastus lateralis muscle. Computer-controlled PPTs were significantly correlated between sites (r > 0.72) and with cuff PPT (r > 0.4). Saline induced pain intensity and duration were correlated between sites (r > 0.39) and with all PPTs (r < −0.41). Conclusions. Pressure pain thresholds at the vastus lateralis are positively associated with knee extensor muscle strength. Different pain sensitivity assessment methods are generally correlated. The cuff PPT and evoked infrapatellar pain seem to reflect the general pain sensitivity. This trial is registered with ClinicalTrials.gov: NCT01351558. PMID:24167727

  3. 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

  4. 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

  5. Catechol-O-methyltransferase Inhibition Increases Pain Sensitivity through Activation of Both β2 and β3 Adrenergic Receptors

    PubMed Central

    Nackley-Neely, Andrea Gail; Tan, Kai Soo; Fecho, Karamarie; Flood, Patrick; Diatchenko, Luda; Maixner, William

    2007-01-01

    Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Our group demonstrated that human genetic variants of COMT are predictive for the development of Temporomandibular Joint Disorder (TMJD) and are associated with heightened experimental pain sensitivity (Diatchenko et al. 2005). Variants associated with heightened pain sensitivity produce lower COMT activity. Here we report the mechanisms underlying COMT-dependent pain sensitivity. To characterize the means whereby elevated catecholamine levels, resulting from reduced COMT activity, modulate heightened pain sensitivity, we administered a COMT inhibitor to rats and measured behavioral responsiveness to mechanical and thermal stimuli. We show that depressed COMT activity results in enhanced mechanical and thermal pain sensitivity. This phenomenon is completely blocked by the nonselective β-adrenergic antagonist propranolol or by the combined administration of selective β2- and β3-adrenergic antagonists, while administration of β1-adrenergic, α-adrenergic, or dopaminergic receptor antagonists fail to alter COMT-dependent pain sensitivity. These data provide the first direct evidence that low COMT activity leads to increased pain sensitivity via a β2/3-adrenergic mechanism. These findings are of considerable clinical importance, suggesting that pain conditions resulting from low COMT activity and/or elevated catecholamine levels can be treated with pharmacological agents that block both β2- and β3-adrenergic receptors. PMID:17084978

  6. Experiential avoidance and anxiety sensitivity as dispositional variables and their relationship to the adjustment to chronic pain.

    PubMed

    Esteve, R; Ramírez-Maestre, C; López-Martínez, A E

    2012-05-01

    Anxiety sensitivity has been included in the fear-avoidance model as a vulnerability factor to explain individual differences in fear of pain. Several studies have suggested that the relationship between anxiety sensitivity and some psychopathological disorders is mediated by experiential avoidance, an affect-related regulatory process that involves unwillingness to endure private experiences. The role of these constructs as vulnerability variables has not been investigated in chronic pain patients. The aim of this study was to investigate the role of anxiety sensitivity and experiential avoidance as dispositional variables in pain fear-avoidance. Two alternative hypothetical models were tested: one in which anxiety sensitivity and experiential avoidance would be independently associated with pain fear-avoidance; and second, one in which experiential avoidance would mediate the relationship between anxiety sensitivity and pain fear-avoidance. The sample was composed of 299 patients with chronic back pain. The postulated relationships were tested using LISREL 8.20 software (Scientific Software International, Chicago, IL, USA) and the generally weighted least squares. The structural equation modelling analyses showed that experiential avoidance and anxiety sensitivity were independently associated with pain fear-avoidance and that anxiety sensitivity had a stronger association with pain fear-avoidance than experiential avoidance. The alternative model, in which experiential avoidance mediates the relationship between anxiety sensitivity and pain fear-avoidance, gave a much worse fit. These results highlight the importance of both anxiety sensitivity and experiential avoidance as variables which could explain individual differences in pain fear-avoidance. Thus, in terms of prevention, it should be a priority to identify patients with increased anxiety sensitivity and experiential avoidance during the first stages of the development of chronic pain conditions. PMID

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

    PubMed

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

    2014-11-01

    The purpose of this study was to translate pain sensitivity questionnaires (PSQ) into the Korean language, perform a cross-cultural adaption of the PSQ, and validate the Korean version of PSQ in patients with degenerative spinal disease. The PSQ was translated forward and backward, cross-culturally adapted by 2 independent translators, and approved by an expert committee. The final Korean version of the PSQ was tested on 72 patients with degenerative spinal disease. Test-retest reliability was evaluated for 60 patients (83%) who completed the second assessment in an interval of 4 weeks. The mean PSQ-minor, PSQ-moderate, and PSQ-total (standard deviation [SD]) were 5.40 (2.02), 6.46 (1.98), and 5.93 (1.93), respectively. The PSQ-total, PSQ-minor, and PSQ-moderate of the Korean version showed very good internal consistencies determined by the Cronbach's α of 0.926, 0.869, and 0.877, respectively. For convergent validity, the PSQ scores of the Korean version showed significant correlations with pain catastrophizing scale (PCS) (r = 0.377, P = 0.002; r = 0.365, P = 0.003; r = 0.362, P = 0.003 for PSQ-total, PSQ-minor, and PSQ-moderate of the Korean version, respectively). For test-retest reliability, the intraclass correlation coefficients were 0.782 for PSQ-total, 0.752 for PSQ-minor, and 0.793 for PSQ-moderate. In conclusion, the validated Korean version of PSQ is a transculturally equivalent, reliable, and valid tool to assess individual pain sensitivity. PMID:24131768

  8. Variation in surgical trauma and baseline pain intensity: effects on assay sensitivity of an analgesic trial.

    PubMed

    Breivik, E K; Björnsson, G A

    1998-08-01

    The aims of this study were to test the hypotheses that the type of 3rd molar removal determines baseline pain and that baseline pain influences analgesic assay sensitivity. Three groups of patients were studied: (i) 100 patients that had one fully erupted maxillary 3rd molar extracted; (ii) 95 patients that had one lower impacted 3rd molar surgically removed; and (iii) 98 patients that had two ipsilateral impacted 3rd molars surgically removed. In a randomized, double-blind fashion, the patients received (every third hour, three times) either: (i) paracetamol 1g; (ii) paracetamol 1g plus codeine 60 mg; or (iii) placebo. Baseline pain intensity (100 mm Visual Analogue Scale) was significantly lower after extraction (8 mm (2-20)) (=median (25th -75th percentile) than after surgical removal of one 3rd molar (35 mm (15-57)), which was significantly lower than pain intensity after surgical removal of two 3rd molars (49 mm (24-82)). Analgesic effects of the active test drugs were superior to placebo. Paracetamol with and without codeine could be distinguished in patients after surgical removal of one 3rd molar. In conclusion, baseline pain was related to the degree of surgical trauma, but large inter-individual variation in baseline pain intensity reduced the ability to distinguish between paracetamol with and without codeine. PMID:9708687

  9. Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits

    PubMed Central

    Kanazawa, Motoyori; Palsson, Olafur S; Thiwan, Syed IM; Turner, Marsha J; van Tilburg, Miranda AL; Gangarosa, Lisa M; Chitkara, Denesh K; Fukudo, Shin; Drossman, Douglas A; Whitehead, William E

    2013-01-01

    Objectives Irritable bowel syndrome (IBS) patients show pain hypersensitivity and hypercontractility in response to colonic or rectal distention. Aims were to determine whether predominant bowel habits and IBS symptom severity are related to pain sensitivity, colon motility, or smooth muscle tone. Methods 129 patients classified as IBS with diarrhea (IBS-D, n=44), IBS with constipation (IBS-C, n=29), mixed IBS (IBS-M, n=45) and unspecified IBS (IBS-U, n=11) based on stool consistency, and 30 healthy controls (HC) were studied. A manometric catheter containing a 600-ml capacity plastic bag was positioned in the descending colon. Pain threshold was assessed using a barostat. Motility was assessed for 10 min with the bag minimally inflated (individual operating pressure or IOP), 10 min at 20 mmHg above the IOP, and for 15-min recovery following bag inflation. Motility was also recorded for 30 min following an 810-kcal meal. Results Compared to HC, IBS patients had lower pain thresholds (medians: 30 vs. 40 mmHg, p<0.01), but IBS subtypes were not different. IBS symptom severity was correlated with pain thresholds (rho=-0.36, p<0.001). During distention, the motility index (MI) was significantly higher in IBS compared to HC (909±73 vs. 563±78, p<0.01). Average barostat bag volume at baseline was higher (muscle tone lower) in HC compared to IBS-D and IBS-M but not compared to IBS-C. The baseline MI and bag volume differed between IBS-D and IBS-C and correlated with symptoms of abdominal distention and dissatisfaction with bowel movements. Pain thresholds and MI during distention were uncorrelated. Conclusions Pain sensitivity and colon motility are independent factors contributing to IBS symptoms. Treatment may need to address both and to be specific to predominant bowel habit. PMID:18684175

  10. The association between spinal cord trauma-sensitive miRNAs and pain sensitivity, and their regulation by morphine

    PubMed Central

    Strickland, Eric R.; Woller, Sarah A.; Hook, Michelle A.; Grau, James W.; Miranda, Rajesh C.

    2014-01-01

    Increased pain sensitivity is a common sequela to spinal cord injury (SCI). Moreover, drugs like morphine, though critical for pain management, elicit pro-inflammatory effects that exacerbate chronic pain symptoms. Previous reports showed that SCI results in the induction and suppression of several microRNAs (miRNAs), both at the site of injury, as well as in segments of the spinal cord distal to the injury site. We hypothesized that morphine would modulate the expression of these miRNAs, and that expression of these SCI-sensitive miRNAs may predict adaptation of distal nociceptive circuitry following SCI. To determine whether morphine treatment further dysregulates SCI-sensitive miRNAs, their expression was examined by qRT-PCR in sham controls and in response to vehicle and morphine treatment following contusion in rats, at either 2 or 15 days post-SCI. Our data indicated that expression of miR1, miR124, and miR129-2 at the injury site predicted the nociceptive response mediated by spinal regions distal to the lesion site, suggesting a molecular mechanism for the interaction of SCI with adaptation of functionally intact distal sensorimotor circuitry. Moreover, the SCI-induced miRNA, miR21 was induced by subsequent morphine administration, representing an alternate, and hitherto unidentified, maladaptive response to morphine exposure. Contrary to predictions, mRNA for the pro-inflammatory interleukin-6 receptor (IL6R), an identified target of SCI-sensitive miRNAs, was also induced following SCI, indicating dissociation between miRNA and target gene expression. Moreover, IL6R mRNA expression was inversely correlated with locomotor function suggesting that inflammation is a predictor of decreased spinal cord function. Collectively, our data indicate that miR21 and other SCI-sensitive miRNAs may constitute therapeutic targets, not only for improving functional recovery following SCI, but also for attenuating the effects of SCI on pain sensitivity. PMID:24867772

  11. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs.

    PubMed

    Woolf, C J; Doubell, T P

    1994-08-01

    Chronic pain is characterized by abnormal sensitivity, which is due to the generation of pain in response to the activation of the low-threshold mechanoreceptive A beta fibres that normally generate innocuous sensations. Three different processes in the spinal cord can account for this dramatic alteration in sensory processing in the somatosensory system: increased excitability, decreased inhibition and structural reorganization. All have been shown to occur and each may contribute separately or together to the wide range of chronic inflammatory and neuropathic pain disorders. The unravelling of the cellular mechanisms involved both offers the potential for developing novel therapeutic strategies, which reduce functional synaptic plasticity and prevent central atrophic and regenerative responses in injured neurones, and illustrates the capacity of the adult nervous system for maladaptive modification. PMID:7812141

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

    PubMed Central

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

    2015-01-01

    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. PMID:25907744

  13. Outcome Measure of Pain in Patients with Lumbar Disc Herniation: Validation Study of the Iranian version of Pain Sensitivity Questionnaire

    PubMed Central

    Azhari, Shirzad; Shahzadi, Sohrab; Nayeb Aghaei, Hossain; Mohammadi, Hassan Reza; Montazeri, Ali

    2016-01-01

    Study Design Cross-sectional. Purpose To translate and culturally adapt an Iranian version of the Pain Sensitivity Questionnaire (PSQ) in Iran. Overview of Literature Instruments measuring patient reported outcomes should satisfy certain psychometric properties. Methods The PSQ was translated following cross-cultural adaptation guidelines. A total of 101 patients with lumbar disc herniation (LDH), and 39 healthy cases were included in the study. All participants completed the PSQ and the Pain Catastrophizing Scale (PCS). The internal consistency, test-retest reliability, known group comparison, criterion validity and item-scale correlations were assessed. Results The mean age of participants was 51.7 years. Reliability, validity and correlation of PSQ and PCS showed satisfactory results. Cronbach's alpha coefficients were 0.81 for PSQ-total, 0.82 for PSQ-minor, and 0.82 for PSQ-moderate. The intraclass correlation coefficients value was 0.84 (0.616–0.932) indicating an excellent test-retest reliability. The instrument discriminated well between sub-groups of patients who differed in a standard predictive measure of LDH surgery (the Finneson–Cooper score). Total PSQ were also significantly correlated with the total scores of the PCS, lending support to its good convergent validity. Additionally, the correlation of each item with its hypothesized domain on the PSQ indicated acceptable results, suggesting that the items had a substantial relationship with their own domains. Conclusions The adapted Iranian PSQ is a valid and reliable questionnaire for the assessment of pain in patients with LDH. PMID:27340527

  14. Central Sensitization and MAPKs are Involved in Occlusal Interference-Induced Facial Pain in Rats

    PubMed Central

    Cao, Ye; Li, Kai; Fu, Kai-Yuan; Xie, Qiu-Fei; Chiang, Chen-Yu; Sessle, Barry J.

    2013-01-01

    We previously developed a rat dental occlusal interference model of facial pain that was produced by bonding a crown onto the right maxillary first molar and was reflected in sustained facial hypersensitivity that was suggestive of the involvement of central sensitization mechanisms. The aim of the present study was to investigate potential central mechanisms involved in the occlusal interference-induced facial hypersensitivity. A combination of behavioral, immunohistochemical, Western blot and electrophysiological recording procedures was used in 98 male adult Sprague-Dawley rats that either received the occlusal interference or were sham-operated or naive rats. Immunohistochemically labeled astrocytes and microglia in trigeminal subnucleus caudalis (Vc) showed morphological changes indicative of astrocyte and microglial activation after the occlusal interference. Prolonged upregulation of p38 MAPK and ERK was also documented in Vc after placement of the occlusal interference, and was expressed in both neurons and glial cells at time points when rats showed peak mechanical facial hypersensitivity. The i.t. administration of the p38 MAPK inhibitor SB203580 to the medulla significantly inhibited the occlusal interference-induced hypersensitivity, and the ERK inhibitor PD98059 produced an even stronger effect. Central sensitization of functionally identified Vc nociceptive neurons following placement of the occlusal interference was also documented by extracellular electrophysiological recordings, and i.t. administration of PD98059 could reverse the neuronal central sensitization. These novel findings suggest that central mechanisms including central sensitization of trigeminal nociceptive neurons and non-neuronal processes involving MAPKs play significant roles in the production of occlusal interference-induced facial pain. Perspective Central mechanisms including trigeminal nociceptive neuronal sensitization, non-neuronal processes involving glial activation and

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review.

    PubMed

    Lluch, E; Torres, R; Nijs, J; Van Oosterwijck, J

    2014-11-01

    Hyperexcitability of the central nervous system (CNS) has been suggested to play an important role in the chronic pain experienced by osteoarthritis (OA) patients. A systematic review following PRISMA guidelines was performed to evaluate the existing evidence from the literature related to the presence of central sensitization (CS) in patients with OA.Electronic databases PubMed and Web of Science were searched to identify relevant articles using pre-defined keywords regarding CS and OA. Full-text clinical reports addressing studies of CS in human adults with chronic complaints due to osteoarthritis were included and screened for methodological quality by two independent reviewers. From the 40 articles that were initially eligible for methodological quality assessment, 36 articles achieved sufficient scores and therefore were discussed. The majority of these studies were case-control studies and addressed OA of the knee joint. Different subjective and objective parameters considered manifestations of CS, which have been previously reported in other chronic pain conditions such as whiplash or rheumatoid arthritis, were established in subjects with OA pain. Overall results suggest that, although peripheral mechanisms are involved in OA pain, hypersensitivity of the CNS plays a significant role in a subgroup of subjects within this population. Although the majority of the literature provides evidence for the presence of CS in chronic OA pain, clinical identification and treatment of CS in OA is still in its infancy, and future studies with good methodological quality are necessary. PMID:24700605

  18. The alteration of pain sensitivity at disease-specific acupuncture points in premenstrual syndrome.

    PubMed

    Chae, Younbyoung; Kim, Hee-Young; Lee, Hwa-Jin; Park, Hi-Joon; Hahm, Dae-Hyun; An, Kyungeh; Lee, Hyejung

    2007-04-01

    Acupuncture points (APs) are well known to be small regions of local or referred pain that are more sensitive than surrounding tissue. Based on bibliographical and clinical data, specific conditions are commonly believed to change the pain sensitivity at corresponding APs. The aim of the present study was to investigate whether the pressure pain threshold (PPT) of specific APs is associated with the severity of premenstrual syndrome. The 46 participants were female students attending a middle school. Premenstrual syndrome (PMS) was measured using a structured questionnaire, the menstruation distress questionnaire (MDQ). High PMS (HP) and low PMS (LP) groups were divided based on their MDQ scores. The PPTs at sites in the leg (the APs SP6, GB39, and LR3 and a non-AP 2-cm anterior to SP6) and in the arm (the APs PC6, TE5, and LI4 and a non-AP 2-cm proximal to PC6) were measured using an algometer. The PPT of the HP group at SP6 was significantly lower than that of the LP group (13.50 +/- 0.73 vs. 16.30 +/- 0.66 kilopascals, P < 0.05), but not at other APs or at non-APs. The findings of our study support the hypothesis that the alteration of pain threshold at specific APs is associated with the severity of corresponding diseases. Further studies are needed to determine whether an observation of pain sensitivity at the APs could be used as an adjunctive tool for the diagnosis of a clinical problem. PMID:17378970

  19. 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

  20. Updating postoperative pain management: from multimodal to context-sensitive treatment.

    PubMed

    Fanelli, G; Berti, M; Baciarello, M

    2008-09-01

    Although a wealth of evidence exists on effective postoperative pain (POP) treatment, surgical patients still suffer from inadequate analgesic regimens, and outcomes have been shown to improve only within the context of tightly controlled, randomized trials. The pathophysiology of pain seems to suggest that analgesic regimens aimed at inhibition of neurotransmission and neuroplastic phenomena should be instituted immediately before the painful stimuli are applied. Several protocols have been proposed, but the final choice should be made according to patients' needs, surgical indications, and institutional resources. Optimal POP management may succeed in improving outcomes only when combined with hospital-wide protocols for early rehabilitation and recovery; in the absence of adequate monitoring, equipment, motivation and coordination, even state-of-the-art techniques may fail to show results in terms of returning to daily life. Analgesic efficacy should always be balanced against safety and the ability to monitor patients in order to reduce complications that may actually impair recovery. A ''context-sensitive'' approach to POP, therefore, is suggested. Context-sensitive analgesia should be instituted as early as deemed necessary to avoid persistent pain, and it should be continued, with different modalities, until full recovery from surgery. In this way, it should constitute a ''bridge'' therapy from surgery to full healing. The use of neuroprotective agents to reduce the risk of postoperative hyperalgesia and other sensory disturbances should be considered in the context of specific surgical interventions. PMID:18762755

  1. Botulinum toxin-A treatment reduces human mechanical pain sensitivity and mechanotransduction.

    PubMed

    Paterson, Kathryn; Lolignier, Stéphane; Wood, John N; McMahon, Stephen B; Bennett, David L H

    2014-04-01

    The mechanisms underlying the analgesic effects of botulinum toxin serotype A (BoNT-A) are not well understood. We have tested the hypothesis that BoNT-A can block nociceptor transduction. Intradermal administration of BoNT-A to healthy volunteers produced a marked and specific decrease in noxious mechanical pain sensitivity, whereas sensitivity to low-threshold mechanical and thermal stimuli was unchanged. BoNT-A did not affect cutaneous innervation. In cultured rodent primary sensory neurons, BoNT-A decreased the proportion of neurons expressing slowly adapting mechanically gated currents linked to mechanical pain transduction. Inhibition of mechanotransduction provides a novel locus of action of BoNT-A, further understanding of which may extend its use as an analgesic agent. PMID:24550077

  2. 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.

  3. 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

  4. 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

    2015-12-01

    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

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

    PubMed

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

    2015-11-01

    Study Design Systematic review. Objectives To elucidate if there is sensitization of the nervous system in those with persistent rotator cuff (shoulder), lateral elbow, patellar, and Achilles tendinopathies. Background Tendinopathy can be difficult to treat, and persistent intractable pain and dysfunction are frequent. It is hypothesized that induction or maintenance of persistent pain in tendinopathy may be, at least in part, based on changes in the nervous system. Methods The PRISMA guidelines were followed. Relevant articles were identified through a computerized search in Embase, PubMed, and Web of Science, followed by a manual search of reference lists of retained articles. To be eligible, studies had to include quantitative sensory testing and evaluate individuals diagnosed with a persistent tendinopathy of the rotator cuff (shoulder), lateral elbow, patella, or Achilles tendon. Methodological quality assessment was evaluated with the Newcastle-Ottawa Scale. Results In total, 16 full-text articles met the criteria for inclusion, of which the majority were case-control studies with heterogeneous methodological quality. No studies on Achilles tendinopathy were found. Mechanical algometry was the predominant quantitative sensory testing used. Lowered pressure pain threshold was observed across different tendinopathies at the site of tendinopathy, as well as at other sites, the latter being suggestive of central sensitization. Conclusion Although more research on sensory abnormalities is warranted, it appears likely that there is an association between persistent tendon pain and sensitization of the nervous system. This evidence is primarily from studies of upper-limb tendinopathy, and caution should be exercised with inference to lower-limb tendinopathy. J Orthop Sports Phys Ther 2015;45(11):864-875. Epub 21 Sep 2015. doi:10.2519/jospt.2015.5895. PMID:26390275

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

    PubMed Central

    Sundstrup, Emil; Jakobsen, Markus D.; Brandt, Mikkel; Jay, Kenneth; Persson, Roger; Andersen, Lars L.

    2015-01-01

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

  7. 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

  8. 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

  9. 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. PMID:25963754

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Autoimmunity contributes to nociceptive sensitization in a mouse model of complex regional pain syndrome.

    PubMed

    Li, Wen-Wu; Guo, Tian-Zhi; Shi, Xiaoyou; Czirr, Eva; Stan, Trisha; Sahbaie, Peyman; Wyss-Coray, Tony; Kingery, Wade S; Clark, J David

    2014-11-01

    Complex regional pain syndrome (CRPS) is a painful, disabling, chronic condition whose etiology remains poorly understood. The recent suggestion that immunological mechanisms may underlie CRPS provides an entirely novel framework in which to study the condition and consider new approaches to treatment. Using a murine fracture/cast model of CRPS, we studied the effects of B-cell depletion using anti-CD20 antibodies or by performing experiments in genetically B-cell-deficient (μMT) mice. We observed that mice treated with anti-CD20 developed attenuated vascular and nociceptive CRPS-like changes after tibial fracture and 3 weeks of cast immobilization. In mice with established CRPS-like changes, the depletion of CD-20+ cells slowly reversed nociceptive sensitization. Correspondingly, μMT mice, deficient in producing immunoglobulin M (IgM), failed to fully develop CRPS-like changes after fracture and casting. Depletion of CD20+ cells had no detectable effects on nociceptive sensitization in a model of postoperative incisional pain, however. Immunohistochemical experiments showed that CD20+ cells accumulate near the healing fracture but few such cells collect in skin or sciatic nerves. On the other hand, IgM-containing immune complexes were deposited in skin and sciatic nerve after fracture in wild-type, but not in μMT fracture/cast, mice. Additional experiments demonstrated that complement system activation and deposition of membrane attack complexes were partially blocked by anti-CD20+ treatment. Collectively, our results suggest that CD20-positive B cells produce antibodies that ultimately support the CRPS-like changes in the murine fracture/cast model. Therapies directed at reducing B-cell activity may be of use in treating patients with CRPS. PMID:25218828

  17. Autoimmunity contributes to nociceptive sensitization in a mouse model of complex regional pain syndrome

    PubMed Central

    Li, Wen-Wu; Guo, Tian-Zhi; Shi, Xiaoyou; Czirr, Eva; Stan, Trisha; Sahbaie, Peyman; Wyss-Coray, Tony; Kingery, Wade S.; Clark, J. David

    2014-01-01

    Complex regional pain syndrome (CRPS) is a painful, disabling, chronic condition whose etiology remains poorly understood. The recent suggestion that immunological mechanisms may underlie CRPS provides an entirely novel framework in which to study the condition and consider new approaches to treatment. Using a murine fracture/cast model of CRPS, we studied the effects of B-cell depletion using anti-CD20 antibodies or by performing experiments in genetically B-cell-deficient (µMT) mice. We observed that mice treated with anti-CD20 developed attenuated vascular and nociceptive CRPS-like changes after tibial fracture and 3 weeks of cast immobilization. In mice with established CRPS-like changes, the depletion of CD-20+ cells slowly reversed nociceptive sensitization. Correspondingly, µMT mice, deficient in producing immunoglobulin M (IgM), failed to fully develop CRPS-like changes after fracture and casting. Depletion of CD20+ cells had no detectable effects on nociceptive sensitization in a model of postoperative incisional pain, however. Immunohistochemical experiments showed that CD20+ cells accumulate near the healing fracture but few such cells collect in skin or sciatic nerves. On the other hand, IgM-containing immune complexes were deposited in skin and sciatic nerve after fracture in wild-type, but not in µMT fracture/cast, mice. Additional experiments demonstrated that complement system activation and deposition of membrane attack complexes were partially blocked by anti-CD20+ treatment. Collectively, our results suggest that CD20-positive B cells produce antibodies that ultimately support the CRPS-like changes in the murine fracture/cast model. Therapies directed at reducing B-cell activity may be of use in treating patients with CRPS. PMID:25218828

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

    PubMed Central

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

    2014-01-01

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

  19. Association between the variable number of tandem repeat polymorphism in the third exon of the dopamine D4 receptor gene and sensitivity to analgesics and pain in patients undergoing painful cosmetic surgery.

    PubMed

    Aoki, Yoshinori; Nishizawa, Daisuke; Kasai, Shinya; Fukuda, Ken-Ichi; Ichinohe, Tatsuya; Yamashita, Shuichiro; Ikeda, Kazutaka

    2013-05-10

    To elucidate the mechanisms of individual differences in pain and analgesic sensitivity, we analyzed the variable number of tandem repeat polymorphism in the third exon of the dopamine D4 receptor gene. Alleles that were less than four repeats long and four or more repeats long were considered Short and Long, respectively. We found that the Short/Short genotype group was significantly more sensitive to pain and less sensitive to analgesics than the Short/Long+Long/Long genotype group. Our data suggest that this polymorphism may predict individual differences in pain and analgesic sensitivity and help achieve adequate pain control in the future. PMID:23458670

  20. 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

  1. Mechanical pain sensitivity of deep tissues in children - possible development of myofascial trigger points in children

    PubMed Central

    2012-01-01

    Background It is still unclear when latent myofascial trigger points (MTrPs) develop during early life. This study is designed to investigate the mechanical pain sensitivity of deep tissues in children in order to see the possible timing of the development of latent MTrPs and attachment trigger points (A-TrPs) in school children. Methods Five hundreds and five healthy school children (age 4- 11 years) were investigated. A pressure algometer was used to measure the pressure pain threshold (PPT) at three different sites in the brachioradialis muscle: the lateral epicondyle at elbow (site A, assumed to be the A-TrP site), the mid-point of the muscle belly (site B, assumed to be the MTrP site), and the muscle-tendon junction as a control site (site C). Results The results showed that, for all children in this study, the mean PPT values was significantly lower (p < 0.05) at the assumed A-TrP site (site A) than at the other two sites, and was significantly lower (p < 0.05) at the assumed MTrP site (site B) than at the control site (site C). These findings are consistent if the data is analyzed for different genders, different dominant sides, and different activity levels. Conclusions It is concluded that a child had increased sensitivity at the tendon attachment site and the muscle belly (endplate zone) after age of 4 years. Therefore, it is likely that a child may develop an A-Trp and a latent MTrP at the brachioradialis muscle after the age of 4 years. The changes in sensitivity, or the development for these trigger points, may not be related to the activity level of children aged 7-11 years. Further investigation is still required to indentify the exact timing of the initial occurrence of a-Trps and latent MTrPs. PMID:22316064

  2. Secreted herpes simplex virus-2 glycoprotein G alters thermal pain sensitivity by modifying NGF effects on TRPV1.

    PubMed

    Cabrera, Jorge Rubén; Viejo-Borbolla, Abel; Alcamí, Antonio; Wandosell, Francisco

    2016-01-01

    Genital herpes is a painful disease frequently caused by the neurotropic pathogen herpes simplex virus type 2 (HSV-2). We have recently shown that HSV-2-secreted glycoprotein G (SgG2) interacts with and modulates the activity of the neurotrophin nerve growth factor (NGF). This interaction modifies the response of the NGF receptor TrkA, increasing NGF-dependent axonal growth. NGF is not only an axonal growth modulator but also an important mediator of pain and inflammation regulating the amount, localization, and activation of the thermal pain receptor transient receptor potential vanilloid 1 (TRPV1). In this work, we addressed whether SgG2 could contribute to HSV-2-induced pain. Injection of SgG2 in the mouse hindpaw produced a rapid and transient increase in thermal pain sensitivity. At the molecular level, this acute increase in thermal pain induced by SgG2 injection was dependent on differential NGF-induced phosphorylation and in changes in the amount of TrkA and TRPV1 in the dermis. These results suggest that SgG2 alters thermal pain sensitivity by modulating TRPV1 receptor. PMID:27576911

  3. Catechol-O-methyltransferase genotype (Val158met) modulates cancer-related fatigue and pain sensitivity in breast cancer survivors.

    PubMed

    Fernández-de-las-Peñas, César; Fernández-Lao, Carolina; Cantarero-Villanueva, Irene; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; del Moral-Avila, Rosario; Arroyo-Morales, Manuel

    2012-06-01

    Cancer-related fatigue and pain after surgery are the most frequent and most incapacitating cancer-related symptoms after breast cancer treatment. Genetic influence of cancer-related fatigue and pain has not been previously investigated. Our aim was to examine the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on cancer-related fatigue, post-mastectomy pain, and pressure pain hypersensitivity in breast cancer survivors. One-hundred and twenty-eight (n = 128) breast cancer survivors who were treated with radiotherapy and chemotherapy participated in this study. After amplifying Val158Met polymorphisms by polymerase chain reaction, COMT genotype was divided into Val/Val, valine/methionine (Val/Met), or Met/Met. The Piper fatigue scale (PFS) was used to assess cancer-related fatigue. Neck and shoulder/axillary pain intensity was assessed with a numerical pain rate scale (0-10). Finally, pressure pain thresholds (PPT) were assessed bilaterally over the C5-C6 zygapophyseal joints, deltoid muscles, second metacarpal, and tibialis anterior muscles. Breast cancer survivors carrying the Met/Met genotype reported higher levels of fatigue (all subscales, P < 0.001), higher neck pain intensity, and lower PPT over C5-C6 joints and deltoid muscles (all, P < 0.001) relative to those with Val/Met or Val/Val genotypes. The results suggest that breast cancer survivors carrying the Met/Met genotype exhibit higher fatigue, neck pain, and pressure pain hypersensitivity over the neck and shoulder area. This study is important because it strives to understand the factors that predispose some breast cancer survivors to more cancer-related fatigue and increased pain sensitivity. PMID:21898113

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

    PubMed Central

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

    2016-01-01

    Objectives 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). Methods 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. Results 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. Conclusions 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. PMID:19850803

  5. 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

  6. 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. PMID:26270592

  7. 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. PMID:26606866

  8. 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

  9. 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. PMID:27375443

  10. 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

  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. Association between KCNJ6 (GIRK2) gene polymorphism rs2835859 and post-operative analgesia, pain sensitivity, and nicotine dependence.

    PubMed

    Nishizawa, Daisuke; Fukuda, Ken-ichi; Kasai, Shinya; Ogai, Yasukazu; Hasegawa, Junko; Sato, Naomi; Yamada, Hidetaka; Tanioka, Fumihiko; Sugimura, Haruhiko; Hayashida, Masakazu; Ikeda, Kazutaka

    2014-01-01

    G-protein-activated inwardly rectifying potassium (GIRK) channels are expressed in many tissues and activated by several Gi/o protein-coupled receptors, such as opioid and dopamine receptors, and thus are known to be involved in the modulation of opioid-induced analgesia, pain, and reward. We focused on a GIRK-channel subunit that plays a pivotal role in the brain, GIRK2, and investigated the contribution of genetic variations of the GIRK2 (KCNJ6) gene to individual differences in the sensitivity to opioid analgesia. In our initial linkage disequilibrium analysis, a total of 27 single-nucleotide polymorphisms (SNPs) were selected within and around the regions of the KCNJ6 gene. Among them, the rs2835859 SNP, for which associations with analgesia and pain have not been previously reported, was selected in the exploratory study as a potent candidate SNP associated with opioid analgesic sensitivity. The results were corroborated in further confirmatory study. Interestingly, this SNP was also found to be associated with sensitivity to both cold and mechanical pain, susceptibility to nicotine dependence, and successful smoking cessation. The results indicate that this SNP could serve as a marker that predicts sensitivity to analgesic and pain and susceptibility to nicotine dependence. PMID:25346042

  13. 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

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

    PubMed Central

    2011-01-01

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

  15. Spinal Manipulative Therapy Has an Immediate Effect on Thermal Pain Sensitivity in People With Low Back Pain: A Randomized Controlled Trial

    PubMed Central

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

    2009-01-01

    Background Current evidence suggests that spinal manipulative therapy (SMT) is effective in the treatment of people with low back pain (LBP); however, the corresponding mechanisms are unknown. Hypoalgesia is associated with SMT and is suggestive of specific mechanisms. Objective The primary purpose of this study was to assess the immediate effects of SMT on thermal pain perception in people with LBP. A secondary purpose was to determine whether the resulting hypoalgesia was a local effect and whether psychological influences were associated with changes in pain perception. Design This study was a randomized controlled trial. Setting A sample of convenience was recruited from community and outpatient clinics. Participants Thirty-six people (10 men, 26 women) currently experiencing LBP participated in the study. The average age of the participants was 32.39 (SD=12.63) years, and the average duration of LBP was 221.79 (SD=365.37) weeks. Intervention and Measurements Baseline demographic and psychological measurements were obtained, followed by quantitative sensory testing to assess temporal summation and Aδ fiber–mediated pain perception. Next, participants were randomly assigned to ride a stationary bicycle, perform low back extension exercises, or receive SMT. Finally, the same quantitative sensory testing protocol was reassessed to determine the immediate effects of each intervention on thermal pain sensitivity. Results Hypoalgesia to Aδ fiber–mediated pain perception was not observed. Group-dependent hypoalgesia of temporal summation specific to the lumbar innervated region was observed. Pair-wise comparisons indicated significant hypoalgesia in participants who received SMT, but not in those who rode a stationary bicycle or performed low back extension exercises. Psychological factors did not significantly correlate with changes in temporal summation in participants who received SMT. Limitations Only immediate effects of SMT were measured, so the authors

  16. Serum Levels of Proinflammatory Cytokines in Painful Knee Osteoarthritis and Sensitization

    PubMed Central

    Imamura, Marta; Ezquerro, Fernando; Marcon Alfieri, Fábio; Vilas Boas, Lucy; Tozetto-Mendoza, Tania Regina; Chen, Janini; Özçakar, Levent; Arendt-Nielsen, Lars

    2015-01-01

    Osteoarthritis (OA) is the most common joint disorder in the world. Among the mechanisms involved in osteoarthritis, biomarkers (cytokines profile) may be related to pain and pain intensity, functional capacity, and pressure pain thresholds (PPT). Thus, the study of these relationships may offer useful information about pathophysiology and associated mechanisms involved in osteoarthritis. Therefore, the objective of this study was to investigate the seric concentration of pro (IL-6, IL-8, and TNF-α) and anti-inflammatory (IL-10) cytokines in patients with painful knee osteoarthritis and to correlate the levels of these biomarkers with the patients' functional capacity and pressure pain threshold (PPT) values. PMID:25821631

  17. 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. PMID:23707281

  18. 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. PMID:21764354

  19. Increased Sensitivity to Inflammatory Pain Induced by Subcutaneous Formalin Injection in Serine Racemase Knock-Out Mice

    PubMed Central

    Tabata-Imai, Ayako; Inoue, Ran; Mori, Hisashi

    2014-01-01

    D-Serine, an endogenous coagonist of the N-methyl-D-aspartate receptor (NMDAR), is widely distributed in the central nervous system and is synthesized from L-serine by serine racemase (SR). NMDAR plays an important role in pain processing including central sensitization that eventually causes hyperalgesia. To elucidate the roles of D-serine and SR in pain transmission, we evaluated the behavioral changes and spinal nociceptive processing induced by formalin using SR knock-out (KO) mice. We found that SR is mainly distributed in lamina II of the dorsal horn of the spinal cord in wild-type (WT) mice. Although the formalin injected subcutaneously induced the biphasic pain response of licking in SR-KO and WT mice, the time spent on licking was significantly longer in the SR-KO mice during the second phase of the formalin test. The number of neurons immunopositive for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK), which are molecular pain markers, in laminae I-II of the ipsilateral dorsal horn was significantly larger in the SR-KO mice. Immunohistochemical staining revealed that the distribution of SR changed from being broad to being concentrated in cell bodies after the formalin injection. On the other hand, the expression level of the cytosolic SR in the ipsilateral dorsal horn significantly decreased. Oral administration of 10 mM D-serine in drinking water for one week cancelled the difference in pain behaviors between WT and SR-KO mice in phase 2 of the formalin test. These findings demonstrate that the SR-KO mice showed increased sensitivity to inflammatory pain and the WT mice showed translocation of SR and decreased SR expression levels after the formalin injection, which suggest a novel antinociceptive mechanism via SR indicating an important role of D-serine in pain transmission. PMID:25133605

  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. 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

  2. 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 ...

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

    PubMed Central

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

    2014-01-01

    In cats, osteoarthritis causes significant chronic pain. Chronicity of pain is associated with changes in the central nervous system related to central sensitization, which have to be quantified. Our objectives were 1) to develop a quantitative sensory testing device in cats for applying repetitive mechanical stimuli that would evoke temporal summation; 2) to determine the sensitivity of this test to osteoarthritis-associated pain, and 3) to examine the possible correlation between the quantitative sensory testing and assessment using other pain evaluation methods. We hypothesized that mechanical sub-threshold repetitive stimuli would evoke temporal summation, and that cats with osteoarthritis would show a faster response. A blinded longitudinal study was performed in 4 non-osteoarthritis cats and 10 cats with naturally occurring osteoarthritis. Quantification of chronic osteoarthritis pain-related disability was performed over a two week period using peak vertical force kinetic measurement, motor activity intensity assessment and von Frey anesthesiometer-induced paw withdrawal threshold testing. The cats afflicted with osteoarthritis demonstrated characteristic findings consistent with osteoarthritis-associated chronic pain. After a 14-day acclimation period, repetitive mechanical sub-threshold stimuli were applied using a purpose-developed device. Four stimulation profiles of predetermined intensity, duration and time interval were applied randomly four times during a four-day period. The stimulation profiles were different (P<0.001): the higher the intensity of the stimulus, the sooner it produced a consistent painful response. The cats afflicted with osteoarthritis responded more rapidly than cats osteoarthritis free (P = 0.019). There was a positive correlation between the von Frey anesthesiometer-induced paw withdrawal threshold and the response to stimulation profiles #2 (2N/0.4 Hz) and #4 (2N/0.4 Hz): Rhos = 0.64 (P = 0.01) and 0.63 (P = 0

  4. Evoked temporal summation in cats to highlight central sensitization related to osteoarthritis-associated chronic pain: a preliminary study.

    PubMed

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

    2014-01-01

    In cats, osteoarthritis causes significant chronic pain. Chronicity of pain is associated with changes in the central nervous system related to central sensitization, which have to be quantified. Our objectives were 1) to develop a quantitative sensory testing device in cats for applying repetitive mechanical stimuli that would evoke temporal summation; 2) to determine the sensitivity of this test to osteoarthritis-associated pain, and 3) to examine the possible correlation between the quantitative sensory testing and assessment using other pain evaluation methods. We hypothesized that mechanical sub-threshold repetitive stimuli would evoke temporal summation, and that cats with osteoarthritis would show a faster response. A blinded longitudinal study was performed in 4 non-osteoarthritis cats and 10 cats with naturally occurring osteoarthritis. Quantification of chronic osteoarthritis pain-related disability was performed over a two week period using peak vertical force kinetic measurement, motor activity intensity assessment and von Frey anesthesiometer-induced paw withdrawal threshold testing. The cats afflicted with osteoarthritis demonstrated characteristic findings consistent with osteoarthritis-associated chronic pain. After a 14-day acclimation period, repetitive mechanical sub-threshold stimuli were applied using a purpose-developed device. Four stimulation profiles of predetermined intensity, duration and time interval were applied randomly four times during a four-day period. The stimulation profiles were different (P<0.001): the higher the intensity of the stimulus, the sooner it produced a consistent painful response. The cats afflicted with osteoarthritis responded more rapidly than cats osteoarthritis free (P = 0.019). There was a positive correlation between the von Frey anesthesiometer-induced paw withdrawal threshold and the response to stimulation profiles #2 (2N/0.4 Hz) and #4 (2N/0.4 Hz): Rhos = 0.64 (P = 0.01) and 0.63 (P = 0

  5. Argument for the need of investigation of the relationship between body fatness and experimental pain sensitivity.

    PubMed

    Astita, Rehab A; Tashani, Osama A; Sharp, Duncan; Johnson, Mark I

    2015-01-01

    In this communication, we argue about the need for an extensive investigation of the relationship between body fatness and fat distribution and experimental pain to explore the factors that might contribute to the increased prevalence of pain conditions in obese individuals. PMID:26085491

  6. 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…

  7. 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

  8. 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. PMID:25750163

  9. The role of experiential avoidance in acute pain tolerance: a laboratory test.

    PubMed

    Feldner, Matthew T; Hekmat, Hamid; Zvolensky, Michael J; Vowles, Kevin E; Secrist, Zachary; Leen-Feldner, Ellen W

    2006-06-01

    The present investigation examined the role of experiential avoidance in terms of acute pain tolerance and subsequent recovery. Seventy nonclinical participants completed the Acceptance and Action Questionnaire and underwent a well-established cold pressor task. Results indicated that individuals reporting higher levels of experiential avoidance had lower pain endurance and tolerance and recovered more slowly from this particular type of aversive event. Consistent with theoretical prediction, these findings suggest that experiential avoidance may play a role in tolerance of acute pain. PMID:15882839

  10. 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

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

    PubMed

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

    2006-01-01

    The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated. PMID:16504836

  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. PMID:25378137

  13. Pain frequency moderates the relationship between pain catastrophizing and pain

    PubMed Central

    Kjøgx, Heidi; Zachariae, Robert; Pfeiffer-Jensen, Mogens; Kasch, Helge; Svensson, Peter; Jensen, Troels S.; Vase, Lene

    2014-01-01

    Background: Pain frequency has been shown to influence sensitization, psychological distress, and pain modulation. The present study examined if pain frequency moderates the relationship between pain catastrophizing and pain. Method: A non-clinical (247 students) and a clinical (223 pain patients) sample completed the Danish versions of the Pain Catastrophizing Scale (PCS), Beck Depression Inventory, and the State Trait Anxiety Inventory and rated pain intensity, unpleasantness and frequency. Results: In both samples, high pain frequency was found to moderate the association between pain catastrophizing and pain intensity, whereas low pain frequency did not. The psychometric properties and the factor structure of the Danish version of the PCS were confirmed. Conclusions: This is the first study to validate the Danish version of the PCS and to show that pain frequency moderates the relationship between pain catastrophizing and reported pain in both non-clinical and clinical populations. PMID:25646089

  14. The Long Term Role of Anxiety Sensitivity and Experiential Avoidance on Pain Intensity, Mood, and Disability among Individuals in a Specialist Pain Clinic.

    PubMed

    Mehta, S; Rice, D; Janzen, S; Serrato, J; Getty, H; Shapiro, A P; Morley-Forster, P; Sequeira, K; Teasell, R W

    2016-01-01

    Background. Anxiety sensitivity (AS) and experiential avoidance (EA) have been shown to have an interactive effect on the response an individual has to chronic pain (CP) potentially resulting in long term negative outcomes. Objective. The current study attempted to (1) identify distinct CP subgroups based on their level of EA and AS and (2) compare the subgroups in terms of mood and disability. Methods. Individuals with CP were recruited from an academic pain clinic. Individuals were assessed for demographic, psychosocial, and personality measures at baseline and 1-year follow-up. A cluster analysis was conducted to identify distinct subgroups of patients based on their level of EA and AS. Differences in clinical outcomes were compared using the Repeated Measures MANOVA. Results. From a total of 229 participants, five clusters were formed. Subgroups with lower levels of AS but similar high levels of EA did not differ in outcomes. Mood impairment was significantly greater among those with high levels of EA compared to lower levels (p < 0.05). Significant improvement in disability (p < 0.05) was only seen among those with lower levels of EA and AS. Conclusions. This cluster analysis demonstrated that EA had a greater influence on mood impairment, while both EA and AS levels affected disability outcomes among individuals with CP. PMID:27445621

  15. Single-Point but Not Tonic Cuff Pressure Pain Sensitivity Is Associated with Level of Physical Fitness – A Study of Non-Athletic Healthy Subjects

    PubMed Central

    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. PMID:25933412

  16. Effects of noise-disturbed sleep—A laboratory study on habituation and subjective noise sensitivity

    NASA Astrophysics Data System (ADS)

    Öhström, E.; Björkman, M.

    1988-04-01

    The effect of road traffic noise from heavy vehicles during the night was investigated in a two week laboratory experiment. Body movements, heart rate, subjective sleep quality, mood and performance was evaluated among two different groups of subjects, non-sensitive and sensitive to noise. Acute physiological effects, increased heart rate and an increased number of body movements, in connection with noise events were found and neither of these reactions decreased towards the end of the noise period. A significant effect on subjective sleep quality was found only among the sensitive subjects. No habititation was seen for the negative influence of noise on sleep quality, mood and performance.

  17. 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. They clearly…

  18. 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.

  19. Intravenous Ibandronate Rapidly Reduces Pain, Neurochemical Indices of Central Sensitization, Tumor Burden, and Skeletal Destruction in a Mouse Model of Bone Cancer

    PubMed Central

    Halvorson, Kyle G.; Sevcik, Molly A.; Ghilardi, Joseph R.; Sullivan, Lucy J.; Koewler, Nathan J.; Bauss, Frieder; Mantyh, Patrick W.

    2008-01-01

    Over half of all chronic cancer pain arises from metastases to bone and bone cancer pain is one of the most difficult of all persistent pain states to fully control. Currently, bone pain is treated primarily by opioid-based therapies, which are frequently accompanied by significant unwanted side effects. In an effort to develop non-opioid-based therapies that could rapidly attenuate tumor-induced bone pain, we examined the effect of intravenous administration of the bisphosphonate, ibandronate, in a mouse model of bone cancer pain. Following injection and confinement of green fluorescent protein-transfected murine osteolytic 2472 sarcoma cells into the marrow space of the femur of male C3H/HeJ mice, ibandronate was administered either as a single dose (300 µg/kg), at day 7 post-tumor injection, when tumor-induced bone destruction and pain were first evident, or in three consecutive doses (100 µg/kg/day) at day 7, 8 and 9 post-tumor injection. Intravenous ibandronate administered once or in three consecutive doses reduced ongoing and movement-evoked bone cancer pain-related behaviors, neurochemical markers of central sensitization, tumor burden and tumor-induced bone destruction. These results support limited clinical trials that suggest the potential of ibandronate to rapidly attenuate bone pain and illuminate the mechanisms that may be responsible for limiting pain and disease progression. PMID:18411018

  20. 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

  1. 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

  2. Laboratory and sonographic findings in dialyzed patients with bilateral chronic knee pain versus dialyzed asymptomatic patients.

    PubMed

    Barisić, Igor; Ljutić, Dragan; Vlak, Tonko; Bekavac, Josip; Janković, Stipan

    2007-06-01

    The aim of this study is to evaluate connection of plasma level of beta2-microglobulin, C-reactive protein and uric acid as well as sonographic parameters like thickness of synovial membrane, thickness of femoral condylar cartilage and presence of joint effusion and Baker's cysts with bilateral knee pain in dialyzed patients, comparing them with parameters in asymptomatic dialyzed patients. Plasma levels of beta2-microglobulin and C-reactive protein were significantly higher in symptomatic patients while uric acid level showed no difference among the groups. In symptomatic patients synovial membrane was thicker and in those patients there were more knee effusions and Baker's cysts. Thickness of femoral condylar cartilage showed no difference between groups. That suggests that inflammatory mechanisms developing from beta2-microglobulin accumulation could be important factor in bilateral knee pain in dialyzed patients even in shorter duration dialysis. PMID:17847928

  3. Gabapentin reverses central pain sensitization following a collagenase-induced intrathalamic hemorrhage in rats

    PubMed Central

    Castel, Aude; Vachon, Pascal

    2014-01-01

    Purpose The treatment of central neuropathic pain remains amongst the biggest challenges for pain specialists. The main objective of this study was to assess gabapentin (GBP), amitriptyline (AMI), and carbamazepine (CARBA) for the treatment of a rodent central neuropathic pain model. Methods Male Sprague Dawley rats were trained on the rotarod, Hargreaves, Von Frey and acetone behavioral tests, and baseline values were obtained prior to surgery. A stereotaxic injection of either a collagenase solution or saline was made in the right ventral posterolateral thalamic nucleus. The rats were tested on days 2, 4, 8, and 11 postsurgery. They were retested at regular intervals from day 15 to day 25 postsurgery, after oral administration of either the vehicle (n=7 and n=8 rats with intracerebral injections of collagenase and saline, respectively) or the different drugs (GBP [60 mg/kg], AMI [10 mg/kg], CARBA [100 mg/kg]; n=8 rats/drug). Results A significant decrease in the mechanical thresholds and no change in heat threshold were observed in both hind limbs in the collagenase group, as we had previously shown elsewhere. Reversal of the mechanical hypersensitivity was achieved only with GBP (P<0.05). AMI and CARBA, at the dosages used, failed to show any effect on mechanical thresholds. Transient cold allodynia was observed in some collagenase-injected rats but failed to be statistically significant. Conclusion Intrathalamic hemorrhaging in the ventrolateral thalamic nucleus induced a bilateral mechanical allodynia, which was reversed by GBP but not AMI or CARBA. PMID:24368890

  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. Evaluation of sensitivity, motor and pain thresholds across the menstrual cycle through medium-frequency transcutaneous electrical nerve stimulation

    PubMed Central

    de Brito Barbosa, Mariana; de Oliveira Guirro, Elaine Caldeira; Nunes, Fabiana Roberta

    2013-01-01

    OBJECTIVES: The aim of this study was to identify variations in nervous thresholds in different phases of the menstrual cycle in eumenorrheic women and users of oral contraceptives. METHOD: An observational study was performed including 56 volunteers, consisting of 30 eumenorrheic women who were non-users of oral contraceptives and 26 users of oral contraceptives. An electrical stimulator was employed to assess their nervous thresholds, with pulses applied at a fixed frequency of 2,500 Hz, modulated at 50 Hz, with phase variances of 20 μs, 50 μs and 100 μs. Sensitivity, motor and pain thresholds were evaluated during five menstrual cycle phases: phase 1 - menstrual, phase 2 - follicular, phase 3 - ovulatory, phase 4 - luteal and phase 5 - premenstrual. RESULTS: The results indicated low sensitivity thresholds of 100 μs for non-users of oral contraceptives and 50 μs for oral contraceptive users in phase 5. Low motor thresholds of 20 μs, 50 μs and 100 μs were observed for non-users of oral contraceptives in phase 5, while that of oral contraceptive users was 100 μs. Finally, a low pain threshold of 100 μs was observed in phase 5, but only in the oral contraceptive group. CONCLUSION: Nervous thresholds vary systematically across the phases of the menstrual cycle, with or without the use of oral contraceptives. These variations should be taken into account during research performed in women. PMID:23917651

  6. 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

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

    PubMed

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

    2016-08-01

    Recent understanding of the systems that mediate complex disease states, has generated a search for molecules that simultaneously modulate more than one component of a pathologic pathway. Chronic pain syndromes are etiologically connected to functional changes (sensitization) in both peripheral sensory neurons and in the central nervous system (CNS). These functional changes involve modifications of a significant number of components of signal generating, signal transducing and signal propagating pathways. Our analysis of disease-related changes which take place in sensory neurons during sensitization led to the design of a molecule that would simultaneously inhibit peripheral NMDA receptors and voltage sensitive sodium channels. In the current report, we detail the selectivity of N,N-(diphenyl)-4-ureido-5,7-dichloro-2-carboxy-quinoline (DCUKA) for action at NMDA receptors composed of different subunit combinations and voltage sensitive sodium channels having different α subunits. We show that DCUKA is restricted to the periphery after oral administration, and that circulating blood levels are compatible with its necessary concentrations for effects at the peripheral cognate receptors/channels that were assayed in vitro. Our results demonstrate that DCUKA, at concentrations circulating in the blood after oral administration, can modulate systems which are upregulated during peripheral sensitization, and are important for generating and conducting pain information to the CNS. Furthermore, we demonstrate that DCUKA ameliorates the hyperalgesia of chronic pain without affecting normal pain responses in neuropathic and inflammation-induced chronic pain models. PMID:27158117

  8. Moving in an Environment of Induced Sensorimotor Incongruence Does Not Influence Pain Sensitivity in Healthy Volunteers: A Randomised Within-Subject Experiment

    PubMed Central

    Wand, Benedict Martin; Szpak, Lareina; George, Pamela J.; Bulsara, Max K.; O’Connell, Neil Edward; Moseley, G. Lorimer

    2014-01-01

    Objectives It has been proposed that in the same way that conflict between vestibular and visual inputs leads to motion sickness, conflict between motor commands and sensory information associated with these commands may contribute to some chronic pain states. Attempts to test this hypothesis by artificially inducing a state of sensorimotor incongruence and assessing self-reported pain have yielded equivocal results. To help clarify the effect sensorimotor incongruence has on pain we investigated the effect of moving in an environment of induced incongruence on pressure pain thresholds (PPT) and the pain experienced immediately on completion of PPT testing. Methods Thirty-five healthy subjects performed synchronous and asynchronous upper-limb movements with and without mirror visual feedback in random order. We measured PPT over the elbow and the pain evoked by testing. Generalised linear mixed-models were performed for each outcome. Condition (four levels) and baseline values for each outcome were within-subject factors. Results There was no effect of condition on PPT (p = 0.887) or pressure-evoked pain (p = 0.771). A sensitivity analysis using only the first PPT measure after each condition confirmed the result (p = 0.867). Discussion Inducing a state of movement related sensorimotor incongruence in the upper-limb of healthy volunteers does not influence PPT, nor the pain evoked by testing. We found no evidence that sensorimotor incongruence upregulates the nociceptive system in healthy volunteers. PMID:24709995

  9. The Repression-Sensitization Dimension in Relation to Impending Painful Stimulation

    ERIC Educational Resources Information Center

    Scarpetti, William L.

    1973-01-01

    The study attempted to replicate previous findings of differences between self-report and physiological indices of disturbance in repressors and sensitizers placed in threatening situations. Results indicate that repressors admit to less anxiety on the self-report measure while producing more physiological reactivity to threat of shock. No such…

  10. Sex differences in effects of excitotoxic spinal injury on below-level pain sensitivity.

    PubMed

    Acosta-Rua, Antonio J; Cannon, Richard L; Yezierski, Robert P; Vierck, Charles J

    2011-10-24

    Effects of excitotoxic injury to the thoracic gray matter on sensitivity to below-level nociceptive stimulation were evaluated for female and male Long-Evans rats. Operant escape and lick/guard (L/G) reflex responses to thermal stimulation were evaluated before and for 13-15 weeks after: 1) injections of quisqualic acid (QUIS) into the thoracic gray matter (T8-9), 2) laminectomy and spinal exposure and penetration without injection (sham) or 3) no surgical procedure (control). L/G responding to heat stimulation (44 °C) was unaffected for females and males following thoracic QUIS injections. Similarly, male escape performance was not significantly altered for 44 °C or 10 °C stimulation after QUIS injections or sham surgery. However, escape testing following QUIS and sham injections revealed increased heat sensitivity (44 °C) and decreased cold sensitivity (10 °C) for females. This selective effect is indicative of altered sympathetic activation by the thoracic injections. The effect of sham surgery suggests that female rats are vulnerable to ischemic injury during exposure and manipulation of the spinal cord. Escape from nociceptive heat and cold sensitivity of control males and females was unchanged over 13-15 weeks of testing. PMID:21943508

  11. Autoantibody pain.

    PubMed

    Goebel, Andreas

    2016-06-01

    As autoantibodies bind to target tissues, Fc-region dependent inflammation can induce pain via mediators exciting nociceptors. But recently another possibility has emerged, where autoantibody binding to nociceptors can directly cause pain, without inflammation. This is thought to occur as a result of Fab-region mediated modification of nerve transduction, transmission, or neuropeptide release. In three conditions, complex regional pain syndrome, anti-voltage gated potassium channel complex autoimmunity, and chronic fatigue syndrome, all associated with no or only little inflammation, initial laboratory-, and clinical trial-results have suggested a potential role for autoantibody-mediated mechanisms. More research assessing the pathogenic roles of autoantibodies in these and other chronic pain conditions is required. The concept of autoantibody-mediated pain offers hope for the development of novel therapies for currently intractable pains. PMID:26883460

  12. Monitoring the sensitivity of the oligochaete Tubifex tubifex in laboratory cultures using three toxicants.

    PubMed

    Maestre, Zuriñe; Martinez-Madrid, Maite; Rodriguez, Pilar

    2009-11-01

    Acute toxicity tests were conducted to assess the sensitivity of laboratory cultured Tubifex tubifex (Annelida, Clitellata), as an intralaboratory quality assurance requirement for the test organisms used in sediment chronic bioassays. Worms were exposed to cadmium, copper, and chromium in water-only 96-h tests, in single metal exposure, over a three-year period. The lethal concentration for the x% of the exposed population (LC(x)), the No-Observable-Effect Concentration (NOEC) and the Lowest-Observable-Effect Concentration (LOEC) were estimated. Based on LC(50) values, the rank of toxicity was Cu(+2)>Cd(+2)>Cr(+6). Sensitivity remained relatively constant during the research period and was comparable with the sensitivity of the same culture stock examined more than 10 years ago. This observed consistency in sensitivity indicates that comparisons between different sediment chronic bioassays conducted during the study period, using T. tubifex worms from the same culture stock, was appropriate. It is necessary to control both worm biomass and age for the acute test in order to standardize the test-organism conditions in intralaboratory quality assurance programs. PMID:19720397

  13. Acute chest pain in the high-sensitivity cardiac troponin era: A changing role for noninvasive imaging?

    PubMed

    Smulders, Martijn W; Kietselaer, Bas L J H; Schalla, Simon; Bucerius, Jan; Jaarsma, Caroline; van Dieijen-Visser, Marja P; Mingels, Alma M A; Rocca, Hans-Peter Brunner-La; Post, Mark; Das, Marco; Crijns, Harry J G M; Wildberger, Joachim E; Bekkers, Sebastiaan C A M

    2016-07-01

    Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal. PMID:27297855

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

    PubMed Central

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

    2013-01-01

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

  15. A preliminary study on how hypohydration affects pain perception.

    PubMed

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

    2016-05-01

    Chronic pain is a prevalent health issue with one in five people suffering from some form of chronic pain, with loss of productivity and medical costs of chronic pain considerable. However, the treatment of pain can be difficult, as pain perception is complex and can be affected by factors other than tissue damage. This study investigated the effect of hypohydration (mild, voluntary dehydration from ∼24 h of limiting fluid intake, mimicking someone drinking less than usual) on a person's pain perception. Seventeen healthy males (age 27 ± 5 years) visited the laboratory on three occasions, once as a familiarization and then twice again while either euhydrated (urine specific gravity: 1.008 ± 0.005) or hypohydrated (urine specific gravity: 1.024 ± 0.003, and -1.4 ± 0.9% body mass). Each visit, they performed a cold pressor test, where their feet were placed in cold water (0-3°C) for a maximum of 4 min. Measures of hydration status, pain sensitivity, pain threshold, and catastrophization were taken. We found that hypohydration predicted increased pain sensitivity (β = 0.43), trait pain catastrophizing, and baseline pain sensitivity (β = 0.37 and 0.47, respectively). These results are consistent with previous research, and suggest that a person's hydration status may be an important factor in their perception of acute pain. PMID:26785699

  16. 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

  17. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Costa, Yuri Martins; Porporatti, André Luís; Hilgenberg-Sydney, Priscila Brenner; Bonjardim, Leonardo Rigoldi; Conti, Paulo César Rodrigues

    2015-01-01

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

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

    PubMed

    Zahari, Zalina; Ismail, Rusli

    2014-01-01

      CYP2D6 polymorphisms show large geographical and interethnic differences. Variations in CYP2D6 activity may impact upon a patient's pain level and may contribute to interindividual variations in the response to opioids. This paper reviews the evidence on how CYP2D6 polymorphisms might influence pain sensitivity and clinical response to codeine and tramadol. For example, it is shown that (1) CYP2D6 poor metabolizers (PMs) may be less efficient at synthesizing endogenous morphine compared with other metabolizers. In contrast, ultra-rapid metabolizers (UMs) may be more efficient than other metabolizers at synthesizing endogenous morphine, thus strengthening endogenous pain modulation. Additionally, for codeine and tramadol that are bioactivated by CYP2D6, PMs may undergo no metabolite formation, leading to inadequate analgesia. Conversely, UMs may experience quicker analgesic effects but be prone to higher mu-opioid-related toxicity. The literature suggested the potential usefulness of the determination of CYP2D6 polymorphisms in elucidating serious adverse events and in preventing subsequent inappropriate selection or doses of codeine and tramadol. Notably, even though many studies investigated a possible role of the CYP2D6 polymorphisms on pain sensitivity, pharmacokinetics and pharmacodynamics of these drugs, the results of analgesia and adverse effects are conflicting. More studies are required to demonstrate genetically determined unresponsiveness and risk of developing serious adverse events for patients with pain and these should involve larger numbers of patients in different population types. PMID:23759977

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

    PubMed Central

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

    2015-01-01

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

  2. 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. PMID:25655774

  3. Laboratory Measurements and Model Sensitivity Studies of Dust Deposition Ice Nucleation

    SciTech Connect

    Kulkarni, Gourihar R.; Fan, Jiwen; Comstock, Jennifer M.; Liu, Xiaohong; Ovchinnikov, Mikhail

    2012-08-16

    We investigated the ice nucleating properties of mineral dust particles to understand the sensitivity of simulated cloud properties to two different representations of contact angle in the Classical Nucleation Theory (CNT). These contact angle representations are based on two sets of laboratory deposition ice nucleation measurements: Arizona Test Dust (ATD) particles of 100, 300 and 500 nm sizes were tested at three different temperatures (-25, -30 and -35 C), and 400 nm ATD and kaolinite dust species were tested at two different temperatures (-30 and -35 C). These measurements were used to derive the onset relative humidity with respect to ice (RH{sub ice}) required to activate 1% of dust particles as ice nuclei, from which the onset single contact angles were then calculated based on CNT. For the probability density function (PDF) representation, parameters of the log-normal contact angle distribution were determined by fitting CNT-predicted activated fraction to the measurements at different RH{sub ice}. Results show that onset single contact angles vary from {approx}18 to 24 degrees, while the PDF parameters are sensitive to the measurement conditions (i.e. temperature and dust size). Cloud modeling simulations were performed to understand the sensitivity of cloud properties (i.e. ice number concentration, ice water content, and cloud initiation times) to the representation of contact angle and PDF distribution parameters. The model simulations show that cloud properties are sensitive to onset single contact angles and PDF distribution parameters. The comparison of our experimental results with other studies shows that under similar measurement conditions the onset single contact angles are consistent within {+-}2.0 degrees, while our derived PDF parameters have larger discrepancies.

  4. Chronic Pain

    MedlinePlus

    ... adults. Common chronic pain complaints include headache, low back pain, cancer pain, arthritis pain, neurogenic pain (pain resulting ... Institute of Neurological Disorders and Stroke (NINDS). Low Back Pain Fact Sheet Back Pain information sheet compiled by ...

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

    PubMed Central

    Azimi, Parisa; Benzel, Edward C.

    2016-01-01

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

  6. 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

  7. 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. PMID:21603055

  8. 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. PMID:27546714

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

    PubMed Central

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

    2014-01-01

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

  10. Parameter Sensitivity and Laboratory Benchmarking of a Biogeochemical Process Model for Enhanced Anaerobic Dechlorination

    NASA Astrophysics Data System (ADS)

    Kouznetsova, I.; Gerhard, J. I.; Mao, X.; Barry, D. A.; Robinson, C.; Brovelli, A.; Harkness, M.; Fisher, A.; Mack, E. E.; Payne, J. A.; Dworatzek, S.; Roberts, J.

    2008-12-01

    A detailed model to simulate trichloroethene (TCE) dechlorination in anaerobic groundwater systems has been developed and implemented through PHAST, a robust and flexible geochemical modeling platform. The approach is comprehensive but retains flexibility such that models of varying complexity can be used to simulate TCE biodegradation in the vicinity of nonaqueous phase liquid (NAPL) source zones. The complete model considers a full suite of biological (e.g., dechlorination, fermentation, sulfate and iron reduction, electron donor competition, toxic inhibition, pH inhibition), physical (e.g., flow and mass transfer) and geochemical processes (e.g., pH modulation, gas formation, mineral interactions). Example simulations with the model demonstrated that the feedback between biological, physical, and geochemical processes is critical. Successful simulation of a thirty-two-month column experiment with site soil, complex groundwater chemistry, and exhibiting both anaerobic dechlorination and endogenous respiration, provided confidence in the modeling approach. A comprehensive suite of batch simulations was then conducted to estimate the sensitivity of predicted TCE degradation to the 36 model input parameters. A local sensitivity analysis was first employed to rank the importance of parameters, revealing that 5 parameters consistently dominated model predictions across a range of performance metrics. A global sensitivity analysis was then performed to evaluate the influence of a variety of full parameter data sets available in the literature. The modeling study was performed as part of the SABRE (Source Area BioREmediation) project, a public/private consortium whose charter is to determine if enhanced anaerobic bioremediation can result in effective and quantifiable treatment of chlorinated solvent DNAPL source areas. The modelling conducted has provided valuable insight into the complex interactions between processes in the evolving biogeochemical systems

  11. 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.

  12. 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

  13. 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. PMID:27505392

  14. GIOVE, a shallow laboratory Ge-spectrometer with 100 μBq/kg sensitivity

    SciTech Connect

    Heusser, G.; Weber, M.; Denz, T.; Hakenmueller, J.; Hofacker, R.; Lackner, R.; Lindner, M.; Maneschg, W.; Reisfelder, M.; Simgen, H.; Schreiner, J.; Stolzenburg, D.; Strecker, H.; Westermann, J.

    2013-08-08

    A new germanium gamma spectrometer called GIOVE (Germanium spectrometer with Inner and Outer Veto) has been set up at the underground/shallow laboratory (15 m w.e.) of MPI-K. Its double plastic scintillator veto system and neutron moderation interlayer lower the background by more than one order of magnitude compared to the other existing spectrometer at this facility. The integral (40-2700 keV) background rate of about 290 counts (day kg){sup −1} is just a factor 4 to 8 above that of the GeMPI spectrometers operated at LNGS (3800 m w.e.) and thus proves that even under shallow overburden sub mBq/kg sensitivities are achievable. Extended material screening and neutron attenuation studies preceded the final design of the spectrometer. The technical realization of the spectrometer is described in detail with special emphasis on the inner veto system. For its optimisation a simulation model was developed for light collection on small low activity PMT’s under various geometrical conditions. Radon suppression is accomplished by employing a gas tight sample container and a nitrogen flushed glove-box system with an airlock. The active volume of the crystal was modelled by absorption scanning measurements and Monte Carlo simulations. The complete shield is implemented in a Geant4 based simulation framework.

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

    PubMed

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

    2015-01-01

    Lumbar disc herniation (LDH) is a major cause of discogenic low back pain and sciatica, but the underlying mechanisms remain largely unknown. Hydrogen sulfide (H2S) is becoming recognized for its involvement in a wide variety of processes including inflammation and nociception. The present study was designed to investigate the roles of the H2S signaling pathway in the regulation of expression and function of purinergic receptors (P2XRs) in dorsal root ganglion (DRG) neurons from rats with LDH. LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. Implantation of autologous NP induced persistent pain hypersensitivity, which was partially reversed by an intrathecal injection of A317491, a potent inhibitor of P2X3Rs and P2X2/3Rs. The NP induced persistent pain hypersensitivity was associated with the increased expression of P2X3Rs, but not P2X1Rs and P2X2Rs, receptors in L5-6 DRGs. NP implantation also produced a 2-fold increase in ATP-induced intracellular calcium signals in DRG neurons when compared to those of controls (P < 0.05). Interestingly, NP implantation significantly enhanced expression of the endogenous hydrogen sulfide producing enzyme, cystathionine-β-synthetase (CBS). Systematic administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, suppressed the upregulation of P2X3R expression and the potentiation of ATP-induced intracellular calcium signals in DRG neurons (P < 0.05). Intrathecal injection of AOAA markedly attenuated NP induced- persistent pain hypersensitivity. Our results suggest that sensitization of P2X3Rs, which is likely mediated by CBS-H2S signaling in primary sensory neurons, contributes to discogenic pain. Targeting CBS/H2S-P2X3R signaling may represent a potential treatment for neuropathic pain caused by LDH. PMID:25885215

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  18. Effects of soil moisture on the temperature sensitivity of soil heterotrophic respiration: a laboratory incubation study.

    PubMed

    Zhou, Weiping; Hui, Dafeng; Shen, Weijun

    2014-01-01

    The temperature sensitivity (Q10) of soil heterotrophic respiration (Rh) is an important ecological model parameter and may vary with temperature and moisture. While Q10 generally decreases with increasing temperature, the moisture effects on Q10 have been controversial. To address this, we conducted a 90-day laboratory incubation experiment using a subtropical forest soil with a full factorial combination of five moisture levels (20%, 40%, 60%, 80%, and 100% water holding capacity--WHC) and five temperature levels (10, 17, 24, 31, and 38°C). Under each moisture treatment, Rh was measured several times for each temperature treatment to derive Q10 based on the exponential relationships between Rh and temperature. Microbial biomass carbon (MBC), microbial community structure and soil nutrients were also measured several times to detect their potential contributions to the moisture-induced Q10 variation. We found that Q10 was significantly lower at lower moisture levels (60%, 40% and 20% WHC) than at higher moisture level (80% WHC) during the early stage of the incubation, but became significantly higher at 20%WHC than at 60% WHC and not significantly different from the other three moisture levels during the late stage of incubation. In contrast, soil Rh had the highest value at 60% WHC and the lowest at 20% WHC throughout the whole incubation period. Variations of Q10 were significantly associated with MBC during the early stages of incubation, but with the fungi-to-bacteria ratio during the later stages, suggesting that changes in microbial biomass and community structure are related to the moisture-induced Q10 changes. This study implies that global warming's impacts on soil CO2 emission may depend upon soil moisture conditions. With the same temperature rise, wetter soils may emit more CO2 into the atmosphere via heterotrophic respiration. PMID:24647610

  19. Assessment of sit-to-stand movement in nonspecific low back pain: a comparison study for psychometric properties of field-based and laboratory-based methods.

    PubMed

    Kahraman, Turhan; Ozcan Kahraman, Buse; Salik Sengul, Yesim; Kalemci, Orhan

    2016-06-01

    One of the most difficult tasks associated with the management of nonspecific low back pain (LBP) is its clinical assessment. Objective functional methods have been developed for assessment. However, few studies have used daily activities such as sit-to-stand (STS). The aim was to compare the psychometric properties of two commonly used STS assessment methods. A test-retest reliability study design was used. Participants with nonspecific LBP performed the 30-s chair stand test (30CST) and the STS test in Balance Master, which measures weight transfer, rising index and centre of gravity sway velocity. The same tests were reperformed after 48-72 h. The intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimal detectable change and coefficient of variation were calculated to compare the reliability. The correlations between the tests, the Oswestry Disability Index and pain intensity were examined for validation. The 30CST had very high intrarater reliability (ICC=0.94). The variables of STS test in Balance Master had moderate intrarater reliability (ICC=0.62-0.69). There were significant correlations between the 30CST, Oswestry Disability Index and pain intensity at activity (P<0.01). The rising index was the only one variable that was significantly correlated with pain intensity at activity (P<0.05). The 30CST as the field-based method to measure STS movement was better than the laboratory-based method in terms of their psychometric properties. Moreover, the 30CST was associated with disability and pain related to LBP. The 30CST is a simple, cheap, less time consuming and psychometrically appropriate method to use in individuals with nonspecific LBP. PMID:27031182

  20. Regional soft tissue pains: alias myofascial pain?

    PubMed

    Tunks, E; Crook, J

    1999-06-01

    This chapter deals with four main questions: what is the evidence that 'myofascial pain' syndromes exist?; what is the evidence that the myofascial pain concept is clinically useful?; what is the evidence that managing patients in terms of the myofascial pain diagnosis confers benefits?; and what is the evidence-based management of myofascial pain? The purpose of a diagnosis is to provide boundaries around subgroups of illness in a population since each subgroup presumably has a different mechanism, natural history, prognosis, course and response to treatment. The current literature is divided in its conceptual approach to the problem of regional musculoskeletal pain. Some authors regard myofascial pain as being distinct from regional musculoskeletal pain while others regard these as synonymous. A postulated theory of the pathophysiology of myofascial pain is discussed. This contrasts with a view that regional myofascial pain represents a non-specific localized pain arising from multiple regional, systemic and psychosocial factors. In order to consider myofascial pain as a distinct diagnosis, it would be necessary to resolve reliability issues in the identification of its critical diagnostic features. Beyond reliability issues, there are also problems of sensitivity and specificity--i.e. of the patient population that it identifies--which must be resolved if controlled trials are to be conducted. The clinical usefulness of the myofascial pain diagnosis is considered with regard to what is believed about the course of healing, the determinants of disability, the course of regional versus widespread musculoskeletal pain, the relationship of musculoskeletal injury to pain, and the evidence-based management of musculoskeletal pain. An epidemiological perspective is proposed with regard to regional musculoskeletal pain. This allows for the identification of operationally defined strata of regional musculoskeletal pain and permits studies in course, prognosis and

  1. An ECVAG inter-laboratory validation study of the comet assay: inter-laboratory and intra-laboratory variations of DNA strand breaks and FPG-sensitive sites in human mononuclear cells.

    PubMed

    Ersson, Clara; Møller, Peter; Forchhammer, Lykke; Loft, Steffen; Azqueta, Amaya; Godschalk, Roger W L; van Schooten, Frederik-Jan; Jones, George D D; Higgins, Jennifer A; Cooke, Marcus S; Mistry, Vilas; Karbaschi, Mahsa; Phillips, David H; Sozeri, Osman; Routledge, Michael N; Nelson-Smith, Kirsty; Riso, Patrizia; Porrini, Marisa; Matullo, Giuseppe; Allione, Alessandra; Stepnik, Maciej; Ferlińska, Magdalena; Teixeira, João Paulo; Costa, Solange; Corcuera, Laura-Ana; López de Cerain, Adela; Laffon, Blanca; Valdiglesias, Vanessa; Collins, Andrew R; Möller, Lennart

    2013-05-01

    The alkaline comet assay is an established, sensitive method extensively used in biomonitoring studies. This method can be modified to measure a range of different types of DNA damage. However, considerable differences in the protocols used by different research groups affect the inter-laboratory comparisons of results. The aim of this study was to assess the inter-laboratory, intra-laboratory, sample and residual (unexplained) variations in DNA strand breaks and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites measured by the comet assay by using a balanced Latin square design. Fourteen participating laboratories used their own comet assay protocols to measure the level of DNA strand breaks and FPG-sensitive sites in coded samples containing peripheral blood mononuclear cells (PBMC) and the level of DNA strand breaks in coded calibration curve samples (cells exposed to different doses of ionising radiation) on three different days of analysis. Eleven laboratories found dose-response relationships in the coded calibration curve samples on two or three days of analysis, whereas three laboratories had technical problems in their assay. In the coded calibration curve samples, the dose of ionising radiation, inter-laboratory variation, intra-laboratory variation and residual variation contributed to 60.9, 19.4, 0.1 and 19.5%, respectively, of the total variation. In the coded PBMC samples, the inter-laboratory variation explained the largest fraction of the overall variation of DNA strand breaks (79.2%) and the residual variation (19.9%) was much larger than the intra-laboratory (0.3%) and inter-subject (0.5%) variation. The same partitioning of the overall variation of FPG-sensitive sites in the PBMC samples indicated that the inter-laboratory variation was the strongest contributor (56.7%), whereas the residual (42.9%), intra-laboratory (0.2%) and inter-subject (0.3%) variations again contributed less to the overall variation. The results suggest that the

  2. Neonatal pain

    PubMed Central

    Walker, Suellen M

    2014-01-01

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

  3. Survey of disc diffusion antimicrobial sensitivity testing in avian bacteriology laboratories and the evaluation of a standardised method.

    PubMed

    Whithear, K G; Htwe, T; Sulaiman, I

    1986-04-01

    A survey was conducted in which 15 laboratories involved in avian bacteriology tested the antimicrobial sensitivity of cultures of Staphylococcus aureus, S. epidermidis, Escherichia coli, Alcaligenes faecalis and Salmonella typhimurium, using the disc diffusion test as routinely practised in each laboratory. Up to 28 different antimicrobials or antimicrobial combinations were used. The most commonly tested agents were ampicillin, benzylpenicillin, chloramphenicol, erythromycin, furazolidone, neomycin, streptomycin, sulphonamide, tetracycline and trimethoprim/sulphonamide. Results between laboratories were compared according to the width of the zone of inhibition (annular radius) where 5 or more laboratories used the same disc content of a particular antimicrobial agent, and on whether a culture was interpreted as being sensitive or resistant to a particular agent. The variation in annular radii about the mean values were less than +/- 2 SD in 39.5% and greater than +/- 3 SD in 32.6% of 43 different antimicrobial/culture combinations involving 8 different agents. The range of annular radii measurements was greatest with trimethoprim/sulphonamide and streptomycin discs and with the S. epidermidis culture. Variation in the interpretation of test results was greatest with the Gram-negative bacteria, where for each of the more frequently tested agents at least one, commonly 2 and sometimes all 3 cultures were reported as sensitive and resistant to the same agent by different laboratories. The calibrated dichotomous sensitivity (CDS) test of Bell (1975, 1984) was evaluated as a standardised disc diffusion procedure and was found to be reproducible and accurate. Results obtained using antimicrobial agents calibrated for use in the CDS test were compared with results obtained in the survey using the same agents or agents showing identical resistance patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3741274

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. The problem of pain.

    PubMed

    Nicholson, Keith; Martelli, Michael F

    2004-01-01

    Pain problems, especially posttraumatic headache, are very common following head trauma. Pain may be the most significant problem, more disabling than any brain or other injuries, and interfering with aspects of cognition or other function. However, posttraumatic headache and most other chronic posttraumatic pain problems remain poorly understood. This article reviews fundamental issues that should be considered in understanding the nature of chronic pain including the distinction between acute and chronic pain; neurobiological distinctions between the lateral and medial pain system; nociceptive versus neuropathic or other central pain; sensitization effects; the widely accepted view of chronic pain as a multidimensional subjective experience involving sensory, motivational-affective and cognitive-behavioral components; the problem of mind-body dualism; the role of psychosocial factors in the onset, maintenance, exacerbation or severity of pain; plus issues of response bias and malingering. PMID:14732827

  7. PC1, a non-peptide PKR1-preferring antagonist, reduces pain behavior and spinal neuronal sensitization in neuropathic mice.

    PubMed

    Guida, F; Lattanzi, R; Boccella, S; Maftei, D; Romano, R; Marconi, V; Balboni, G; Salvadori, S; Scafuro, M A; de Novellis, V; Negri, L; Maione, S; Luongo, L

    2015-01-01

    Peripheral neuropathy is characterized by abnormal pain responses triggered by the release of several mediators and neuronal hyperexcitability at the spinal cord level. Emerging evidence indicates that the enhanced activity of dorsal horn neurons requires communication with glia and microglia, cells that are physiologically involved in neuronal wellbeing. Prokineticins (PKs), which include PK1 and PK2, represent a novel family of chemokines characterized by a unique structural motif comprising five disulfide bonds. They are expressed in the peripheral and central nervous system. PKs bind two G protein coupled receptors, PKR1 and PKR2, and participate in the regulation of several biological processes, including pain sensation. This study aimed to investigate the anti-nociceptive effect of PC1, a non-peptide PKR1-preferring antagonist, in a mouse model of neuropathic pain. To do this, we assessed the activity of spinal cord nociceptive neurons as well as astrocyte and microglia phenotypes after repeated administration of PC1 in vivo. PC1 treatment strongly delayed the development of thermal hyperalgesia and tactile and mechanical allodynia. It also reduced spinal microglial and glial activation 8 days post injury in spared nerve injury (SNI) mice. Neuropathic mice showed an increased level of PK2 protein in the spinal cord, mostly in astrocytes. PC1 treatment completely reversed the increased responsiveness to mechanical stimuli, the decreased threshold of neuronal activation, and the increased spontaneous activity that were observed in nociceptive specific (NS) neurons of SNI mice. PMID:25434589

  8. Groin pain

    MedlinePlus

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

  9. 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

  10. 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.

  11. Association between genetic polymorphisms in Ca(v)2.3 (R-type) Ca2+ channels and fentanyl sensitivity in patients undergoing painful cosmetic surgery.

    PubMed

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

    2013-01-01

    Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca(2+) channels (VACCs) play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Ca(v)2.3 (R-type) VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide polymorphisms (SNPs) of the human CACNA1E (calcium channel, voltage-dependent, R type, alpha 1E subunit) gene that encodes Cav2.3 VACCs influence the analgesic effects of opioids. Thus, the present study examined associations between fentanyl sensitivity and SNPs in the human CACNA1E gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. We first conducted linkage disequilibrium (LD) analyses of 223 SNPs in a region that contains the CACNA1E gene using genomic samples from 100 patients, and a total of 13 LD blocks with 42 Tag SNPs were observed within and around the CACNA1E gene region. In the preliminary study using the same 100 genomic samples, only the rs3845446 A/G SNP was significantly associated with perioperative fentanyl use among these 42 Tag SNPs. In a confirmatory study using the other 255 genomic samples, this SNP was also significantly associated with perioperative fentanyl use. Thus, we further analyzed associations between genotypes of this SNP and all of the clinical data using a total of 355 samples. The rs3845446 A/G SNP was associated with intraoperative fentanyl use, 24 h postoperative fentanyl requirements, and perioperative fentanyl use. Subjects who carried the minor G allele required significantly less fentanyl for pain control compared with subjects who did not carry this allele. Although further validation is needed, the present findings show the possibility of the involvement of CACNA1E gene

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

    ERIC Educational Resources Information Center

    Chang, Ming-Mei; Lovett, Janice

    2011-01-01

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

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

    PubMed

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

    2015-06-01

    Acetaminophen, an effective and popular over-the-counter pain reliever (e.g., the active ingredient in Tylenol), has recently been shown to blunt individuals' reactivity to a range of negative stimuli in addition to physical pain. Because accumulating research has shown that individuals' reactivity to both negative and positive stimuli can be influenced by a single factor (an idea known as differential susceptibility), we conducted two experiments testing whether acetaminophen blunted individuals' evaluations of and emotional reactions to both negative and positive images from the International Affective Picture System. Participants who took acetaminophen evaluated unpleasant stimuli less negatively and pleasant stimuli less positively, compared with participants who took a placebo. Participants in the acetaminophen condition also rated both negative and positive stimuli as less emotionally arousing than did participants in the placebo condition (Studies 1 and 2), whereas nonevaluative ratings (extent of color saturation in each image; Study 2) were not affected by drug condition. These findings suggest that acetaminophen has a general blunting effect on individuals' evaluative and emotional processing, irrespective of negative or positive valence. PMID:25862546

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

    NASA Astrophysics Data System (ADS)

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

    1998-12-01

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

  15. Efficacy of toltrazuril in broilers and development of a laboratory model for sensitivity testing of Eimeria field isolates.

    PubMed

    Vertommen, M H; Peek, H W; van der Laan, A

    1990-07-01

    (1) The efficacy of toltrazuril (Baycox) against coccidiosis was established on a broiler farm in an intermittent application during five consecutive growing periods. Treated birds were fed a broiler ration without anticoccidials. The efficacy of Baycox was compared with the nicarbazin-salinomycin shuttle. It was concluded that Baycox retarded the onset of Eimeria infection for several weeks. During the fifth rearing period coccidiosis problems emerged on the farm in all birds during medication, suggesting development of resistance. (2) During a laboratory experiment the efficacy of Baycox was studied in birds after inoculation with different numbers of oocysts at 7, 10 or 15 days of age. Baycox was applied at 10 and 11 days of age. In all cases medication with Baycox protected birds from coccidiosis during a period of at least 7 days. This effect of Baycox could be due to the long-existing tissue levels of the product and its metabolites as well as its specific effect on the second generation of schizonts. (3) In another laboratory experiment coccidia obtained from field trials were tested for sensitivity to Baycox in conjunction with two strains obtained from farms were coccidiosis emerged during application. The inoculation model developed in this study was used for sensitivity testing. One of the Eimeria strains tested was resistant to the product, one strain was tolerant and the remaining two strains, including the control strain, were fully sensitive to Baycox. PMID:2219660

  16. Measurement of Trigeminal Neuralgia Pain: Penn Facial Pain Scale.

    PubMed

    Lee, John Y K

    2016-07-01

    Pain is a subjective experience that cannot be directly measured. Therefore, patient-reported outcome is one of the currently accepted methods to capture pain intensity and its impact on activities of daily living. This article focuses on five patient-reported outcomes that have been used to measure trigeminal neuralgia pain-Visual Analog Scale, numeric rating scale, Barrow Neurological Institute Pain Intensity Score, McGill Pain Questionnaire, and Penn Facial Pain Scale. Each scale is evaluated for its practicality, applicability, comprehensiveness, reliability, validity, and sensitivity to measuring trigeminal neuralgia pain. PMID:27324999

  17. Systematic pain assessment in horses.

    PubMed

    de Grauw, J C; van Loon, J P A M

    2016-03-01

    Accurate recognition and quantification of pain in horses is imperative for adequate pain management. The past decade has seen a much needed surge in formal development of systematic pain assessment tools for the objective monitoring of pain in equine patients. This narrative review describes parameters that can be used to detect pain in horses, provides an overview of the various pain scales developed (visual analogue scales, simple descriptive scales, numerical rating scales, time budget analysis, composite pain scales and grimace scales), and highlights their strengths and weaknesses for potential clinical implementation. The available literature on the use of each pain assessment tool in specific equine pain states (laminitis, lameness, acute synovitis, post-castration, acute colic and post-abdominal surgery) is discussed, including any problems with sensitivity, reliability or scale validation as well as translation of results to other clinical pain states. The review considers future development and further refinement of currently available equine pain scoring systems. PMID:26831169

  18. Chronic Pain

    MedlinePlus

    ... your pain. Medicines used for chronic pain include pain relievers, antidepressants, and anticonvulsants. Different types of medicines help ... If your doctor recommends an over-the-counter pain reliever, read and follow the instructions on the box. ...

  19. Flank pain

    MedlinePlus

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

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

    PubMed

    Dunn, Glynis

    2016-01-01

    The accuracy of poliovirus surveillance is largely dependent on the quality of the cell lines used for virus isolation, which is the foundation of poliovirus diagnostic work. Many cell lines are available for the isolation of enteroviruses, whilst genetically modified L20B cells can be used as a diagnostic tool for the identification of polioviruses. To be confident that cells can consistently isolate the virus of interest, it is necessary to have a quality assurance system in place, which will ensure that the cells in use are not contaminated with other cell lines or microorganisms and that they remain sensitive to the viruses being studied.The sensitivity of cell lines can be assessed by the regular testing of a virus standard of known titer in the cell lines used for virus isolation. The titers obtained are compared to previously obtained titers in the same assay, so that any loss of sensitivity can be detected.However, the detection of cell line cross contamination is more difficult. DNA bar coding is a technique that uses a short DNA sequence from a standardized position in the genome as a molecular diagnostic assay for species-level identification. For almost all groups of higher animals, the cytochrome c oxidase subunit 1 of mitochondrial DNA (CO1) is emerging as the standard barcode region. This region is 648 nucleotide base pairs long in most phylogenetic groups and is flanked by regions of conserved sequences, making it relatively easy to isolate and analyze. DNA barcodes vary among individuals of the same species to a very minor degree (generally less than 1-2 %), and a growing number of studies have shown that the COI sequences of even closely related species differ by several per cent, making it possible to identify different species with high confidence. PMID:26983732

  1. [Chronic pain and rehabilitation].

    PubMed

    Berker, Ender; Dinçer, Nilay

    2005-04-01

    The perception and interpretation of pain is the end point of an interaction of cognitive, cultural, and environmental factors and this complex interaction effects the pain response and quality of life of each person which shows that pain perception and the verbal and behavioral response shows variations and is specific for each patient. Chronic pain can be due to Fibromyalgia Syndrome (FMS) and Neuropathic Pain (NP) where the underlying pathophysiologic mechanisms are being revealed or it can be chronic low back pain (CLBP) where pain persists in spite of healing of tissue and no underlying pathologic mechanism can be defected. Central sensitization, inhibition of descending pain inhibitory systems, functional changes in autonomic nervous system amd neurotransmitter as well as changes in stress response system are factors contributing to the initiation and maintenance of pain and cognitive, behavioral factors are also important contributors in chronic pain. Biopsychosocial and biomedical mechanisms should be assessed in the rehabilitation interventions. The aims of rehabilitation in chronic pain are to increase activity tolerance, functional capacity and to decrease socio-economic loads. The targets of activity should be physical, functional and social. Psychologic based programs as cognitive-behavioral techniques and operant conditioning are also valid procedures in rehabilitation of chronic pain patients. Rehabilitation should be multidisciplinary and of long-term targeted to valid out-come for success. PMID:15977088

  2. Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

    PubMed

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

    2016-07-01

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

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

    PubMed Central

    Sanders, Justin L; Kent, Michael L

    2012-01-01

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

  4. Pain and the ethics of pain management.

    PubMed

    Edwards, R B

    1984-01-01

    In this article I clarify the concepts of 'pain', 'suffering', 'pains of body', 'pains of soul'. I explore the relevance of an ethic to the clinical setting which gives patients a strong prima facie right to freedom from unnecessary and unwanted pain and which places upon medical professionals two concomitant moral obligations to patients. First, there is the duty not to inflict pain and suffering beyond what is necessary for effective diagnosis, treatment and research. Next, there is the duty to do all that can be done to relieve all the pain and suffering which can be alleviated. I develop in some detail that individuality of pain sensitivity must be taken into account in fulfilling these obligations. I explore the issue of the relevance of informed consent and the right to refuse treatment to the matter of pain relief. And I raise the question of what conditions, if any, should override the right to refuse treatment where pain relief is of paramount concern. PMID:6710192

  5. The genetics of pain and pain inhibition.

    PubMed Central

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

    1996-01-01

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

  6. Postamputation pain: studies on mechanisms.

    PubMed

    Nikolajsen, Lone

    2012-10-01

    Amputation is followed by both painful and non-painful phantom phenomena in a large number of amputees. Non-painful phantom sensations rarely pose any clinical problem, but 60-80% of all amputees also experience painful sensations (i.e. phantom pain) located to the missing limb. The severity of phantom pain usually decreases with time, but severe pain persists in 5-10% of patients. Pain in the residual limb (i.e. stump pain) is another consequence of amputation. Both stump and phantom pain can be very difficult to treat. Treatment guidelines used for other neuropathic pain conditions are probably the best approximation, especially for the treatment of stump pain. The aim of the present doctoral thesis was to explore some of the mechanisms underlying pain after amputation. Ten studies were carried out (I-X). My PhD thesis from 1998 dealt with pain before the amputation and showed that preamputation pain increases the risk of phantom pain after amputation (I). A perioperative epidural blockade, however, did not reduce the incidence of pain or abnormal sensory phenomena after amputation (II, III). The importance of sensitization before amputation for the subsequent development of pain is supported by study IV, in which pressure pain thresholds obtained at the limb before amputation were inversely related to stump and phantom pain after 1 week. Afferent input from the periphery is likely to contribute to postamputation pain as sodium channels were upregulated in human neuromas (VI), although neuroma removal did not always alleviate phantom pain (V). Sensitization of neurons in the spinal cord also seems to be involved in pain after amputation as phantom pain was reduced by ketamine, an NMDA-receptor antagonist. Another NMDA-receptor antagonist, memantine, and gabapentin, a drug working by binding to the δ2α-subunit of voltage-gated calcium channels, had no effect on phantom pain (VII-IX). Supraspinal factors are also important for pain after amputation as

  7. Laboratory evaluation of Pacific herring (Clupea pallasi) embryo sensitivity to Prudhoe Bay crude oil

    SciTech Connect

    Kocan, R.; Hose, J.E.; Brown, E.; Baker, T.

    1995-12-31

    Pacific herring were collected in Prince William Sound and artificially spawned onto glass slides. The fertile eggs were exposed to a seawater extract of Prudhoe Bay crude oil (9.67 mg*L HMW and 64 mg*L{sup {minus}1} LMW) in artificial seawater in a static renewal system beginning about 18 h post fertilization. From the stock, a series of exposure concentrations of hydrocarbons was made down to 0.01 mg*L{sup {minus}1}. Chemical analyses demonstrated that over 85% of the LMW hydrocarbons evaporated during the first 24 h of each exposure. Incubation of seawater with and without petroleum extract had constant values of 10.2--10.4 mg O{sup 2}*L{sup {minus}1}, pH of 8.4 and salinity of 29.7--30.3 ppt. Genetic damage was the most sensitive biomarker for oil exposure, followed by physical deformities, reduced mitotic activity, lower hatch weight and precocious hatching. A doubling of background genetic damage occurred at 0.01 mg*L{sup {minus}1} petroleum extract and significant increases in damage occurred in proportion to increasing amounts of extract. The EC{sub 50} for larval deformities was < 0.48 mg*L{sup {minus}1}, mitoses were significantly reduced at 0.1 mg*L{sup {minus}1} , and larval weights were depressed at all exposure concentrations. Premature hatching occurred in embryos exposed to concentrations of petroleum hydrocarbons above 0.24 mg*L{sup {minus}1}. The types of genetic damage, physical deformities, precocious hatch and low hatch weight were similar to that observed in wild Prince William Sound herring larvae immediately following the Exxon Valdez oil spill in 1989.

  8. Cancer pain

    SciTech Connect

    Swerdlow, M.; Ventafridda, V.

    1987-01-01

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

  9. Back Pain

    MedlinePlus

    ... Back Pain Find a Clinical Trial Journal Articles Back Pain March 2015 Handout on Health: Back Pain This publication is for people who have back ... to discuss them with your doctor. What Is Back Pain? Back pain is an all-too-familiar problem ...

  10. Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo.

    PubMed Central

    Stacher, G; Steinringer, H; Schneider, S; Mittelbach, G; Winklehner, S; Gaupmann, G

    1986-01-01

    Models with experimentally induced pain in healthy man might be useful for the screening for analgesic effects of new drugs. Experimental pain models have been shown to discriminate reliably between the effects of opioid analgesics and placebo but their sensitivity to nonsteroidal anti-inflammatory agents is disputed. This study investigated whether it would be possible by using electrically and thermally induced cutaneous pain to discriminate reliably the effects of single oral doses of 75 and 150 mg diclofenac sodium on the one hand and 60 mg codeine on the other from those of placebo. Forty-eight healthy subjects participated each in four experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised eight series of measurements, two before and six after drug administration, carried out at 30 min intervals. Diclofenac sodium produced significant dose-related increases of threshold and tolerance to electrically and threshold to thermally induced pain. Codeine 60 mg was significantly superior to placebo in all pain measures. Its analgesic effects were stronger than those of diclofenac 75 mg but weaker than those of diclofenac 150 mg. Neither 150 mg nor 75 mg diclofenac caused more side effects than placebo, whereas codeine 60 mg elicited a high frequency of side effects. No severe adverse effects occurred after any one treatment. The results suggest that both electrically and thermally induced cutaneous pain are well suited to evaluate analgesic effects not only of opioids but also of nonsteroidal anti-inflammatory drugs. PMID:3947505

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  12. Neck pain

    MedlinePlus

    ... Alternative Names Pain - neck; Neck stiffness; Cervicalgia; Whiplash Images Neck pain Whiplash Location of whiplash pain References ... pubmed/19272509 . Read More Diskectomy Foraminotomy Laminectomy Spinal fusion Patient Instructions Spine surgery - discharge Update Date 3/ ...

  13. Pain Relievers

    MedlinePlus

    Pain relievers are medicines that reduce or relieve headaches, sore muscles, arthritis, or other aches and pains. There ... also have a slightly different response to a pain reliever. Over-the-counter (OTC) medicines are good for ...

  14. Back Pain

    MedlinePlus

    ... BACK PAIN? There are many possible causes of low back pain, including stretched (strained) muscles, torn or stretched (sprained) ... appear to be at an increased risk for low back pain in comparison to the general population (estimates range ...

  15. Elbow pain

    MedlinePlus

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

  16. Eye pain

    MedlinePlus

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

  17. Heel pain

    MedlinePlus

    Pain - heel ... Heel pain is most often the result of overuse. Rarely, it may be caused by an injury. Your heel ... on the heel Conditions that may cause heel pain include: When the tendon that connects the back ...

  18. Wrist pain

    MedlinePlus

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

  19. Depression, Pain, and Pain Behavior.

    ERIC Educational Resources Information Center

    Keefe, Francis J.; And Others

    1986-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  1. The Pharmacology of Visceral Pain.

    PubMed

    Johnson, Anthony C; Greenwood-Van Meerveld, Beverley

    2016-01-01

    Visceral pain describes pain emanating from the internal thoracic, pelvic, or abdominal organs. Unlike somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. While current therapeutics provides some relief from somatic pain, drugs used for treatment of chronic visceral pain are typically less efficacious and limited by multiple adverse side effects. Thus, the treatment of visceral pain represents a major unmet medical need. Further, more basic research into the physiology and pathophysiology of visceral pain is needed to provide novel targets for future drug development. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. However, persistent stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders. We will focus on stress-induced exacerbation of chronic visceral pain and provide supporting evidence that centrally acting drugs targeting the pain and stress-responsive brain regions may represent a valid target for the development of novel and effective therapeutics. PMID:26920016

  2. [Pain and opioids].

    PubMed

    Murányi, Marianna; Radák, Zsolt

    2008-12-14

    Noxious stimuli cause pain to protect the body from harmful situations and attract attention to pathophysiologic changes of the body. Specific receptors of pain (nociceptors) can be found all over our body. Pain initiates protecting mechanisms such as vegetative and motor reflexes, and emotional, behavioral changes. However, chronic pain is practically useless and leads to psychopathological changes. There are several ways to relieve pain including non-steroid anti-inflammatory agents, opioids, neurosurgical and non-invasive methods. Central and peripheral effects of opioids can be realized through opioid receptors of the central and the enteric nervous system. In the central nervous system, they can inhibit the perception of pain or change the emotional reactions. Opioids are indicated in postoperative pain, neuropathic pain and cancer. However, the use of opioids has severe side-effects such as breathing depression and the development of tolerance and dependence which do not make opioids optimal painkillers. There are several laboratories in Hungary and abroad working on the design of optimal pain relievers. Furthermore, the euphoric effects of opioids lead to abuse which makes the research important on the mechanisms of opioid addiction. Taken together, opioid research, the design of new compounds and the exploration of the mechanisms of opiate addiction are very important. PMID:19073443

  3. Seismic moment tensors of acoustic emissions recorded during laboratory rock deformation experiments: sensitivity to attenuation and anisotropy

    NASA Astrophysics Data System (ADS)

    Stierle, Eva; Vavryčuk, Václav; Kwiatek, Grzegorz; Charalampidou, Elli-Maria; Bohnhoff, Marco

    2016-04-01

    Seismic moment tensors can provide information on the size and orientation of fractures producing acoustic emissions (AEs) and on the stress conditions in the sample. The moment tensor inversion of AEs is, however, a demanding procedure requiring carefully calibrated sensors and accurate knowledge of the velocity model. In field observations, the velocity model is usually isotropic and time independent. In laboratory experiments, the velocity is often anisotropic and time dependent and attenuation might be significant due to opening or closure of microcracks in the sample during loading. In this paper, we study the sensitivity of the moment tensor inversion to anisotropy of P-wave velocities and attenuation. We show that retrieved moment tensors critically depend on anisotropy and attenuation and their neglect can lead to misinterpretations of the source mechanisms. The accuracy of the inversion also depends on the fracturing mode of AEs: tensile events are more sensitive to P-wave anisotropy and attenuation than shear events. We show that geometry of faulting in anisotropic rocks should be studied using the source tensors, since the P- and T-axes of the moment tensors are affected by velocity anisotropy and deviate from the true orientation of faulting. The stronger the anisotropy is, the larger the deviations are. Finally, we prove that the moment tensor inversion applied to a large dataset of AEs can be utilized to provide information on the attenuation parameters of the rock sample. The method is capable of measuring anisotropic attenuation in the sample and allows for detection of dilatant cracking according to the stress regime.

  4. Evaluation of an optimized protocol using human peripheral blood monocyte derived dendritic cells for the in vitro detection of sensitizers: Results of a ring study in five laboratories.

    PubMed

    Reuter, Hendrik; Gerlach, Silke; Spieker, Jochem; Ryan, Cindy; Bauch, Caroline; Mangez, Claire; Winkler, Petra; Landsiedel, Robert; Templier, Marie; Mignot, Aurelien; Gerberick, Frank; Wenck, Horst; Aeby, Pierre; Schepky, Andreas

    2015-08-01

    Allergic contact dermatitis is a delayed T-cell mediated allergic response associated with relevant social and economic impacts. Animal experiments (e.g. the local lymph node assay) are still supplying most of the data used to assess the sensitization potential of new chemicals. However, the 7th amendment to the EU Cosmetic Directive have introduced a testing ban for cosmetic ingredients after March 2013. We have developed and optimized a stable and reproducible in vitro protocol based on human peripheral blood monocyte derived dendritic cells to assess the sensitization potential of chemicals. To evaluate the transferability and the predictivity of this PBMDCs based test protocol, a ring study was organized with five laboratories using seven chemicals with a known sensitization potential (one none-sensitizer and six sensitizers, including one pro-hapten). The results indicated that this optimized test protocol could be successfully transferred to all participating laboratories and allowed a correct assessment of the sensitization potential of the tested set of chemicals. This should allow a wider acceptance of PBMDCs as a reliable test system for the detection of human skin sensitizers and the inclusion of this protocol in the toolbox of in vitro methods for the evaluation of the skin sensitization potential of chemicals. PMID:25868915

  5. Back Pain

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Back Pain Information Page Condensed from Low Back Pain Fact ... en Español Additional resources from MedlinePlus What is Back Pain? Acute or short-term low back pain generally ...

  6. Pelvic Pain

    MedlinePlus

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

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

    PubMed

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

    2016-01-01

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

  8. Painful Shoulder in Swimmers: A Diagnostic Challenge.

    ERIC Educational Resources Information Center

    McMaster, William C.

    1986-01-01

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

  9. Chronicity of orofacial pain.

    PubMed

    Gerschman, J A

    2000-10-01

    Acute and chronic orofacial pain continues to be poorly understood and managed. The National Health and Medical Research Council of Australia (NHMRC) 1999 report on acute pain management promotes the development of evidence based clinical practice guidelines aimed at improving both the quality of health care and health outcomes in medical and dental practice in Australia. Nerve signals arising from sites of tissue or nerve injury lead to long term changes in the central nervous system and the amplification and persistence of pain. These nociceptor activity-induced neuronal changes known as central sensitization, have important clinical implications in the development of new approaches to the management of persistent pain. These findings and implications are discussed in relationship to poorly managed and understood conditions such as oral dysaesthesia, burning mouth syndrome, atypical facial pain/atypical odontalgia, peripheral nerve injury, deafferentation and phantom tooth syndrome. PMID:11709938

  10. Oxytocin-induced membrane hyperpolarization in pain-sensitive dorsal root ganglia neurons mediated by Ca(2+)/nNOS/NO/KATP pathway.

    PubMed

    Gong, L; Gao, F; Li, J; Li, J; Yu, X; Ma, X; Zheng, W; Cui, S; Liu, K; Zhang, M; Kunze, W; Liu, C Y

    2015-03-19

    Oxytocin (OT) plays an important role in pain modulation and antinociception in the central nervous system. However, little is known about its peripheral effects. This study was conducted to investigate the effect of OT on the electrical properties of neurons in the dorsal root ganglia (DRG) and the underlying mechanisms. DRG neurons from adult rats were acutely dissociated and cultured. Intracellular Ca(2+) was determined by fluorescent microscopy using an indicator dye. The electrical properties of DRG neurons were tested by patch-clamp recording. The oxytocin receptor (OTR) and neuronal nitric oxide synthase (nNOS) on DRG neurons were assessed with immunofluorescence assays. OTR co-localized with nNOS in most of Isolectin B4 (IB4)-binding cultured DRG neurons in rats. OT decreased the excitability, increased the outward current, and evoked the membrane hyperpolarization in cultured DRG neurons. Sodium nitroprusside (SNP), the donor of nitric oxide (NO), exerted similar effects as OT on the membrane potential of cultured DRG neurons. OT increased the production of NO in DRGs and cultured DRG neurons. Pre-treatment of the OTR antagonist atosiban or the selective nNOS inhibitor N-Propyl-l-arginine (NPLA) significantly attenuated the hyperpolarization effect evoked by OT. OT produced a concentration-dependent increase in intracellular Ca(2+) in DRG neurons that responds to capsaicin, which can be attenuated by atosiban, but not by NPLA. OT-evoked membrane hyperpolarization and increase of outward current were distinctly attenuated by glibenclamide, a blocker of ATP-sensitive K(+) (KATP) channel. OT might be an endogenous antinociceptive agent and the peripheral antinociceptive effects of OT are mediated by activation of the Ca(2+)/nNOS/NO/KATP pathway in DRG neurons. PMID:25617653