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Sample records for laboratory pain sensitivity

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2013-01-01

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

  3. Pain sensitivity and modulation in primary insomnia.

    PubMed

    Haack, M; Scott-Sutherland, J; Santangelo, G; Simpson, N S; Sethna, N; Mullington, J M

    2012-04-01

    Sleep of good quantity and quality is considered a biologically important resource necessary to maintain homeostasis of pain-regulatory processes. To assess the role of chronic sleep disturbances in pain processing, we conducted laboratory pain testing in subjects with primary insomnia. Seventeen participants with primary insomnia (mean ± SEM 22.6 ± 0.9 yrs, 11 women) were individually matched with 17 healthy participants. All participants wore an actigraph device over a 2-week period and completed daily sleep and pain diaries. Laboratory pain testing was conducted in a controlled environment and included (1) warmth detection threshold testing, (2) pain sensitivity testing (threshold detection for heat and pressure pain), and (3) tests to access pain modulatory mechanisms (pain facilitation and inhibition). Primary insomnia subjects reported experiencing spontaneous pain on twice as many days as healthy controls during the at-home recording phase (p < 0.05). During laboratory testing, primary insomnia subjects had lower pain thresholds than healthy controls (p < 0.05 for heat pain detection threshold, p < 0.08 for pressure pain detection threshold). Unexpectedly, pain facilitation, as assessed with temporal summation of pain responses, was reduced in primary insomnia compared to healthy controls (p < 0.05). Pain inhibition, as assessed with the diffuse noxious inhibitory control paradigm (DNIC), was attenuated in insomnia subjects when compared to controls (p < 0.05). Based on these findings, we propose that pain-inhibitory circuits in patients with insomnia are in a state of constant activation to compensate for ongoing subclinical pain. This constant activation ultimately may result in a ceiling effect of pain-inhibitory efforts, as indicated by the inability of the system to adequately function during challenge. PMID:22396081

  4. Altered Pain Sensitivity in Elderly Women with Chronic Neck Pain

    PubMed Central

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

    2015-01-01

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

  5. 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

  6. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    PubMed Central

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

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

  7. 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

  8. Implicit operant learning of pain sensitization.

    PubMed

    Hölzl, Rupert; Kleinböhl, Dieter; Huse, Ellena

    2005-05-01

    Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain behavior, but it is not clear whether and how this extends to pain perception itself. The fear-avoidance theory suggests that hypersensitivity may be induced by anticipatory pain avoidance learned through negative reinforcement by acute reductions of pain and fear. But the precise mechanism of the assumed 'sensory decalibration' has not been specified. The present study with healthy subjects investigated whether operant learning of enhanced short-term sensitization may provide the 'proximal' mechanism and whether gradual learning of hypersensitivity can take place without subjects' awareness. We used an experimental model of implicit learning based on a behavioral adjustment method of sensitization measurement developed and validated previously, combining it with standard methods of operant response shaping of increased sensitization or habituation. Results indicated that operant discrimination training with reinforcement of short-term sensitization in the seconds range can produce gross up or down changes in sensitivity within an hour without subjects' awareness of reinforcement contingencies. Consequently, implicit learning of enhanced pain sensitization may be a suitable model to investigate operant plasticity of pain perception in addition to basic sensory and neuronal mechanisms and to link these with the clinical construct of pain-fear avoidance.

  9. Prediction of pain sensitivity in healthy volunteers

    PubMed Central

    Ravn, Pernille; Frederiksen, Rune; Skovsen, Anders P; Christrup, Lona L; Werner, Mads U

    2012-01-01

    Purpose The primary objective of the present study was to evaluate predictive parameters of the acute pain score during induction of an inflammatory heat injury. Patients and methods Healthy volunteers (50 females/50 males) were included in the study. The predictive potential of gender, anthropometric (body surface area, body mass index), psychological (anxiety, depression, vulnerability), and psychophysical (quantitative sensory testing, conditioned pain modulation) variables in estimating the pain response to a validated heat injury (47°C, 7 minutes, area 12.5 cm2) were investigated. All assessments were made in duplicate sessions separated by 21 days (median). Results There were three main findings in this study. First, a predictive model of pain sensitivity during the heat injury, including both genders and using multiple regression technique, could account for 28% of the variance (P < 0.0001), but gender-related differences in the final model could not be demonstrated. Second, the results confirmed significant gender-related differences in perception of electrical, pressure, and cold pressor stimuli (P < 0.002). Third, positive correlations between anthropometric data and pain perception during electrical and pressure stimuli were demonstrated (P < 0.001 and P < 0.005, respectively). Conclusion The study demonstrated predictability of acute pain sensitivity, and although gender-related differences in pain perception were demonstrated, no gender-related differences in pain sensitivity could be shown. Interestingly, positive correlations between anthropometric data and pain perception were shown for the first time. PMID:23055774

  10. 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

  11. 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.

  12. Increased pain sensitivity in alcohol withdrawal syndrome.

    PubMed

    Jochum, Thomas; Boettger, Michael K; Burkhardt, Christin; Juckel, Georg; Bär, Karl-Jürgen

    2010-08-01

    Withdrawal from analgesic and addictive substances such as opioids or ethanol is associated with increased sensitivity to sensory stimulation in animal models. Here, we investigated perception of innocuous and noxious thermal or electric stimuli applied to the left hand or sternum in 30 male patients undergoing withdrawal from alcohol, 30 male abstained alcoholics and matched controls. The alcohol withdrawal scale and the Banger score were obtained to estimate the severity of withdrawal. In addition, the Beck depression inventory was used to estimate the influence of depressive symptoms on pain perception. The data presented provide substantial evidence that subjects undergoing alcohol withdrawal show increased heat pain sensitivity. Interestingly, this effect was observed both on the left hand and sternum. Pain thresholds and tolerances of electric stimuli did not differ between groups. However, in a subgroup analysis, a higher sensitivity for electrical pain thresholds and tolerances was observed in those patients that were identified to require pharmacological treatment for withdrawal according to disease severity. Furthermore, the perceived painful thermal and electrical sensation was substantially influenced by the affective state of patients. No differences were found between patients of the abstained group and control subjects for any pain parameter. In conclusion, we demonstrate withdrawal-induced hyperalgesia upon thermal stimulation in patients. Since the influence of affective symptoms on pain perception during withdrawal is remarkable, we assume that peripheral and central mechanisms might account for this finding, which should be assessed in detail in future studies.

  13. 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…

  14. Pain Sensitivity and Recovery From Mild Chronic Sleep Loss

    PubMed Central

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

    2012-01-01

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

  15. The effect of disgust on pain sensitivity.

    PubMed

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

    2015-01-01

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

  16. The effect of disgust on pain sensitivity.

    PubMed

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

    2015-01-01

    Experiencing the emotion of disgust leads to delayed up-regulation of immune-related functions, increased core-body temperature and reduced appetite. These changes parallel those of the acute phase response, which occurs when a pathogen is detected by the immune system. Here we examined whether a further predicted aspect of the acute phase response is evident following disgust induction, namely increased pain sensitivity. Participants attended a two-session experiment. On one session they experienced an emotion induction (being randomly assigned to either disgust, negative or positive groups) and on the other they received a neutral control induction. Before and after each induction, and at 15 and 30min post-induction, participants engaged in a cold-pressor task, rating pain intensity at 10s intervals for 90s on each occasion. Relative to neutral control and pre-test, average pain intensity decreased then increased across time following the disgust induction, with the reverse pattern in the negative and positive emotion inductions. These findings are the first to suggest that disgust may lead to an increase in pain sensitivity over a time course paralleling changes observed for core-body temperature and immune-related function, although the mechanisms underpinning these effects remain to be identified. PMID:25447331

  17. Napping Reverses Increased Pain Sensitivity Due to Sleep Restriction

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. 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

  2. Pain sensitivity and headache: an examination of the central theory.

    PubMed

    Marlowe, N I

    1992-01-01

    The central theory of headache was investigated by examining pain sensitivity in headache sufferers and headache-free controls. Headache subjects had lower pain threshold and tolerance levels than controls for electrical stimulation of the finger. Headache subjects also had a lesser tolerance for pain induced by the application of ice to the temporal region, but there was no significant difference between groups on temporal ice pain threshold. Sensitivity to finger pain was not affected by the presence or absence of headache at the time of testing. No significant differences between tension and migraine subjects were observed; neither were headache subjects, reporting unilateral headaches, significantly more sensitive to temporal ice pain on the side affected by headache. It was concluded that headache sufferers may be more sensitive to pain than headache-free persons but, that this heightened sensitivity is not specific to the head, and in itself, seems unable to account for the locus of headache. PMID:1538347

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

    PubMed

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

    2014-01-01

    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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Methods for measuring pain in laboratory animals.

    PubMed

    Graham, Dustin M

    2016-03-01

    Pain is one of the most important variables that members of the lab animal science community try to control and minimize, and it is a critical topic of research in clinical and basic sciences. Objective measurements of pain severity, especially in non-verbal animals that are used as disease models, can be difficult to obtain, but several developments in behavioral neuroscience are making the measurement of pain more consistent, automated and accurate.

  9. The role of sensitization in musculoskeletal shoulder pain

    PubMed Central

    Borstad, John; Woeste, Christopher

    2015-01-01

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

  10. Cortical thickness and pain sensitivity in zen meditators.

    PubMed

    Grant, Joshua A; Courtemanche, Jérôme; Duerden, Emma G; Duncan, Gary H; Rainville, Pierre

    2010-02-01

    Zen meditation has been associated with low sensitivity on both the affective and the sensory dimensions of pain. Given reports of gray matter differences in meditators as well as between chronic pain patients and controls, the present study investigated whether differences in brain morphometry are associated with the low pain sensitivity observed in Zen practitioners. Structural MRI scans were performed and the temperature required to produce moderate pain was assessed in 17 meditators and 18 controls. Meditators had significantly lower pain sensitivity than controls. Assessed across all subjects, lower pain sensitivity was associated with thicker cortex in affective, pain-related brain regions including the anterior cingulate cortex, bilateral parahippocampal gyrus and anterior insula. Comparing groups, meditators were found to have thicker cortex in the dorsal anterior cingulate and bilaterally in secondary somatosensory cortex. More years of meditation experience was associated with thicker gray matter in the anterior cingulate, and hours of experience predicted more gray matter bilaterally in the lower leg area of the primary somatosensory cortex as well as the hand area in the right hemisphere. Results generally suggest that pain sensitivity is related to cortical thickness in pain-related brain regions and that the lower sensitivity observed in meditators may be the product of alterations to brain morphometry from long-term practice.

  11. Experimental Pain Responses Support Peripheral and Central Sensitization in Patients with Unilateral Shoulder Pain

    PubMed Central

    Coronado, Rogelio A.; Simon, Corey B.; Valencia, Carolina; George, Steven Z.

    2013-01-01

    Objective The aims of this study were to 1) examine the pattern of experimental pain responses in the affected and non-affected extremities in patients with shoulder pain and 2) explore the intra-individual association between sensitization states derived from experimental pain testing. Methods Experimental pain responses from 58 patients with shoulder pain (17 females, ages 18 to 52) were compared to those from 56 age- and sex-matched healthy volunteers (16 females, ages 21 to 58). Experimental pain responses included pressure pain threshold (PPT), thermal pain threshold and tolerance, and suprathreshold heat pain response (SHPR). Comparisons were made between the affected and non-affected extremity of clinical participants and the average response of extremities in healthy participants. Peripheral and central sensitization indexes were computed for clinical participants using standardized scores and percentile cut-offs based on the data from the healthy control sample. Experimental pain responses in clinical participants observed beyond the 25th and 75th percentile of healthy control sample responses were used for investigation of intra-individual association of sensitization states. Results PPT on the affected side acromion and masseter of clinical participants were diminished compared to their non-affected side (p < 0.015). Bilateral sensitivity in clinical participants was noted for PPT at the acromion and SHPR (p < 0.015). Peripheral and central sensitization indexes demonstrated that individuals with shoulder pain present with variable patterns of peripheral and central sensitization. Conclusions Collectively, experimental pain responses supported peripheral and central sensitization in response to pressure and thermal stimuli. No clear association was made between individuals exhibiting peripheral or central sensitization and suggests heterogeneity in pain processing in this clinical population. PMID:23619203

  12. 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

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

    PubMed Central

    2016-01-01

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

  14. 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

  15. 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

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

    PubMed Central

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

    2014-01-01

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

  17. 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

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

    PubMed

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

    2008-11-15

    Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic. PMID:18774227

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

    PubMed

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

    2008-11-15

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

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

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. 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

  3. 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

  4. [Assessment of pain sensitivity in neonates with surgical pathology].

    PubMed

    Mel'nikova, N I; Dzemeshko, E Iu; Strogonov, I A; Vorob'ev, V V

    2011-01-01

    Definition of pain in newborns with surgical pathology in the traditional way (change the child's behavior, skin color, heart rate, mean arterial pressure, body temperature, blood gas parameters) is subjective. The "Med-Storm" pain stress detector, manufactured by "Med-Storm Innovation AS" (Norway) allows the quantification of pain during and after surgery in infants. For a small sample, specificity was 76%, sensitivity--89%. Important indicator was the peak skin conductance. The change in the area under the curve was less often, but indicated the need of analgesia dose change.

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. 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

  8. 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

  9. Mildly negative social encounters reduce physical pain sensitivity.

    PubMed

    Borsook, Terry K; MacDonald, Geoff

    2010-11-01

    While previous research has demonstrated a reduction in physical pain sensitivity in response to social exclusion, the manipulations employed have arguably been far removed from typical daily experience. The purpose of this study was to investigate the effects of relatively ordinary social encounters on the perception of pain. Healthy participants rated the intensity and unpleasantness of painful stimuli before and after engaging in a structured interaction with a confederate who was instructed to either be warm and friendly or indifferent. A control group was asked to perform a similar structured activity, but alone. Consistent with predictions, participants who experienced the mildly negative social exchange reported lower pain intensity and unpleasantness after the encounter relative to baseline, whereas those exposed to the positive social exchange did not evidence any change in pain ratings. These results were not mediated by changes in mood or perceived connectedness. If mildly negative social encounters can provoke an analgesic effect, it is possible that social hypoalgesia may be considerably more commonplace than previously realized. Discussion focuses on the role of stress-induced hypoalgesia, and the implications of the results for clinical assessments of pain.

  10. 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

  11. Effects of naltrexone on pain sensitivity and mood in fibromyalgia: no evidence for endogenous opioid pathophysiology.

    PubMed

    Younger, Jarred W; Zautra, Alex J; Cummins, Eric T

    2009-01-01

    The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg) at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.

  12. Anxiety sensitivity and its impact on pain experiences and conditions: a state of the art.

    PubMed

    Stewart, Sherry H; Asmundson, Gordon J G

    2006-01-01

    This paper serves as an introduction to the special issue of Cognitive Behaviour Therapy devoted to the topic of anxiety sensitivity (AS) and its impact on pain experiences and conditions. We provide a historical overview of relevant cognitive behavioural models of chronic pain, summarize recent models incorporating the AS construct, and introduce the papers in the special issue. These papers are organized into two sets--basic laboratory-based investigations and relatively more applied studies. We attempt to highlight some of the most important findings from each of these investigations and studies, in turn. Then, we consider several important conclusions derived from the set of special issue papers and the implications of these for the practice of cognitive-behavioural interventions with pain populations. Finally, we make several suggestions for directions for future investigations in this burgeoning area of cognitive behavioural research and practice.

  13. Selective disturbance of pain sensitivity after social isolation.

    PubMed

    Tuboly, Gabor; Benedek, György; Horvath, Gyöngyi

    2009-01-01

    The effects of social isolation or NMDA-receptor antagonists on pain sensitivity have repeatedly been described. However, the mechanisms underlying the alterations of pain perception in these models still remain a matter of debate. Thus, we aimed to determine the long-lasting effects of subchronic ketamine treatment and social isolation on the C- and Adelta-fiber-mediated nociception. Wistar rats after weaning (21-23 days old) were either housed individually or grouped for 21 days. The animals were treated daily for 14 days with either ketamine (30 mg/kg) or saline. On the 21st day, tail-flick latency was determined at 48 degrees C (C-fiber activation) and 52 degrees C (affects mainly Adelta-fibers), and rats were rehoused. Tail-flick test was repeated 2 and 4 weeks later. On the 5th week, carrageenan-induced heat hyperalgesia was determined on paw-withdrawal test before and after morphine treatment (1, 2 or 3 mg/kg). Regarding tail-flick latencies at 48 degrees C, juvenile isolation, but not ketamine resulted in a significantly enhanced pain threshold (p<0.001) throughout the investigation period, while the changes at 52 degrees C were not significant. In addition, both isolation and ketamine treatments enhanced the antihyperalgesic effect of 2 mg/kg morphine. In summary, juvenile isolation exerts a long-lasting effect on acute heat pain sensitivity, disturbing primarily the C-fiber-linked pain pathways, suggesting a selective disruption in the parallel sensory pathways. Since both social isolation and NMDA treatment are well-known animal models of schizophrenia, our results showed that juvenile isolation but not ketamine administration can simulate hypoalgesia associated with this disease. PMID:18761027

  14. Nicotine Withdrawal and Stress-Induced Changes in Pain Sensitivity: A Cross-sectional Investigation between Abstinent Smokers and Nonsmokers

    PubMed Central

    Nakajima, Motohiro; al’Absi, Mustafa

    2014-01-01

    Chronic smoking has been linked with alterations in endogenous pain regulation. These alterations may be pronounced when individuals quit smoking because nicotine withdrawal produces a variety of psychological and physiological symptoms. Smokers interested in quitting (n=98) and nonsmokers (n=37) completed a laboratory session including cold pressor (CPT) and heat thermal pain. Smokers set a quit date and completed the session after 48 hours of abstinence. Participants completed the pain assessments once post rest and once post stress. Cardiovascular and nicotine withdrawal measures were collected. Smokers showed blunted cardiovascular responses to stress relative to nonsmokers. Only nonsmokers had greater pain tolerance to CPT post stress than post rest. Lower systolic blood pressure was related to lower pain tolerance. These findings suggest that smoking withdrawal is associated with blunted stress response and increased pain sensitivity. PMID:24934193

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

    PubMed

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

    2010-04-01

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

  16. 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

  17. Genes contributing to pain sensitivity in the normal population: an exome sequencing study.

    PubMed

    Williams, Frances M K; Scollen, Serena; Cao, Dandan; Memari, Yasin; Hyde, Craig L; Zhang, Baohong; Sidders, Benjamin; Ziemek, Daniel; Shi, Yujian; Harris, Juliette; Harrow, Ian; Dougherty, Brian; Malarstig, Anders; McEwen, Robert; Stephens, Joel C; Patel, Ketan; Menni, Cristina; Shin, So-Youn; Hodgkiss, Dylan; Surdulescu, Gabriela; He, Wen; Jin, Xin; McMahon, Stephen B; Soranzo, Nicole; John, Sally; Wang, Jun; Spector, Tim D

    2012-01-01

    Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to search for rare gene variants (MAF<5%) influencing pain sensitivity, we explored the genetic variation in individuals' responses to experimental pain. Quantitative sensory testing to heat pain was performed in 2,500 volunteers from TwinsUK (TUK): exome sequencing to a depth of 70× was carried out on DNA from singletons at the high and low ends of the heat pain sensitivity distribution in two separate subsamples. Thus in TUK1, 101 pain-sensitive and 102 pain-insensitive were examined, while in TUK2 there were 114 and 96 individuals respectively. A combination of methods was used to test the association between rare variants and pain sensitivity, and the function of the genes identified was explored using network analysis. Using causal reasoning analysis on the genes with different patterns of SNVs by pain sensitivity status, we observed a significant enrichment of variants in genes of the angiotensin pathway (Bonferroni corrected p = 3.8×10(-4)). This pathway is already implicated in animal models and human studies of pain, supporting the notion that it may provide fruitful new targets in pain management. The approach of sequencing extreme exome variation in normal individuals has provided important insights into gene networks mediating pain sensitivity in humans and will be applicable to other common complex traits.

  18. Pubertal status moderates the association between mother and child laboratory pain tolerance

    PubMed Central

    Tsao, Jennie CI; Li, Ning; Parker, Delana; Seidman, Laura C; Zeltzer, Lonnie K

    2014-01-01

    BACKGROUND: There is limited information regarding the relationship between parent and child responses to laboratory pain induction in the absence of experimental manipulation. OBJECTIVES: To assess the association between responses to cold and pressure pain tasks in 133 nonclinical mothers and children (mean age 13.0 years; 70 girls), and the moderating effects of child sex and pubertal status on these mother-child relationships. METHODS: Mothers and children independently completed the cold and pressure pain tasks. Multiple linear regression analyses examined the association between mothers’ and children’s laboratory pain responses. The moderating effects of child sex and pubertal status were tested in the linear models by examining the interaction among mother laboratory pain responses, and child sex and pubertal status. RESULTS: Mothers’ cold pain anticipatory anxiety and pressure pain intensity were associated with children’s pressure pain anticipatory anxiety. Mothers’ pressure pain tolerance was associated with children’s pain tolerance for both the cold and pressure pain tasks. Mothers’ cold pain tolerance was associated with children’s pressure pain tolerance. Pubertal status moderated two of the three significant mother-child pain tolerance relationships, such that the associations held for early pubertal but not for late pubertal children. Sex did not moderate mother-child pain associations. CONCLUSIONS: The results indicate that mother-child pain relationships are centred primarily on pain avoidance behaviour, particularly among prepubertal children. These findings may inform interventions focused on pain behaviours, with a particular emphasis on mothers of prepubertal children, to reduce acute pain responses in their children. PMID:24367794

  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. Menstrual cycle, beta-endorphins, and pain sensitivity in premenstrual dysphoric disorder.

    PubMed

    Straneva, Patricia A; Maixner, William; Light, Kathleen C; Pedersen, Cort A; Costello, Nancy L; Girdler, Susan S

    2002-07-01

    This study examined pain sensitivity and pain modularity mechanisms (e.g., beta-endorphin levels, blood pressure) in women with premenstrual dysphoric disorder (PMDD; n = 27) and healthy controls (n = 27) during the follicular and luteal phases of the menstrual cycle. Physiological measures were taken during rest and ischemic pain testing. In both cycle phases, PMDD women (a) displayed lower resting cortisol and beta-endorphin levels and (b) exhibited shorter pain threshold and tolerance times and greater pain unpleasantness ratings during pain. PMDD women also reported greater pain unpleasantness and intensity and had lower beta-endorphin levels in their luteal phase and tended to display higher blood pressure levels at rest and during pain testing. Results suggest that endogenous opioids may be pathophysiologically relevant to PMDD and that the hypothalamic-pituitary-gonadal axis may modulate pain sensitivity in PMDD.

  1. 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

  2. Neurophysiology of Cancer Pain: From the Laboratory to the Clinic.

    PubMed

    Regan; Peng; Chan

    1999-01-01

    Pain is one of the most distressing symptoms associated with cancer. Basic science research has provided much insight into the mechanisms of peripheral and central pain and the actions of new drugs. Despite these advances, pain accompanying malignancy can be difficult to treat. Pain most commonly presents when the tumor has invaded somatic,visceral, or neural structures. An understanding of pain mechanisms is essential when deciding on the appropriate treatment. New therapeutic options have been developed and will hopefully provide clinicians with tools to successfully alleviate cancer pain.

  3. 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.

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

    PubMed

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

    2006-08-01

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

  5. Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

    PubMed

    Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

    2016-10-01

    The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations. PMID:27649042

  6. Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

    PubMed

    Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

    2016-10-01

    The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations.

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

    PubMed

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

    2008-10-15

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

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. 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.

  11. 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

  12. 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.

  13. Tough guys or sensitive guys? Disentangling the role of examiner sex on patient pain reports

    PubMed Central

    Vigil, Jacob M; Alcock, Joe

    2014-01-01

    BACKGROUND: Experimental and clinical pain studies are conflicting regarding whether individuals report heightened or dampened pain sensitivity in the presence of other men or women. OBJECTIVES: In the present preliminary study, two small medical record reviews of patients admitted for emergency care were conducted to examine the possibility that patients may report differential pain intensity to male and female health care examiners. The study also sought to determine whether these effects are moderated by and, thus, only detectable by examining patients at different pain (debilitation) levels. METHODS: Pain intensity scores were extracted from two medical record reviews of patients admitted for emergency care (n=64 and n=135, respectively). Pain intensity was measured using an 11-point numerical scale during standard triage assessments and the sex of the examiner was recorded. RESULTS: Mean pain scores reported to male and female emergency staff did not differ in either set of medical records. However, when patients were split between low and high pain levels, male patients reported higher pain scores to male practitioners when experiencing relatively low pain levels, and both male and female patients reported higher pain scores to female practitioners when experiencing relatively high pain levels. DISCUSSION: The statistical magnitudes of these effects were large, suggesting that this phenomenon may be a pervasive feature in clinical settings and experimental pain studies. CONCLUSION: These preliminary findings warrant larger-scale investigations of social contextual influences on patient pain reports, which are necessary for creating more standardized protocols for reliably assessing and treating patient pain experiences. PMID:24511573

  14. Pain tolerance, pain sensitivity, and accessibility of aggression-related schemata in parents at-risk for child physical abuse.

    PubMed

    Hiraoka, Regina; Crouch, Julie L; Reo, Gim; Wagner, Michael; Milner, Joel S; Skowronski, John J

    2014-11-01

    This study examined whether parents with varying degrees of child physical abuse (CPA) risk differed in pain tolerance, pain sensitivity, and accessibility of aggression-related schemata. Participants included 91 (51 low CPA risk and 40 high CPA risk) general population parents. Participants were randomly assigned to complete either an easy or a difficult anagram task. Pain tolerance and pain sensitivity were assessed using a cold pressor task. Accessibility of aggression-related schemata was assessed at the outset of the data collection session and at the end of the session using a word completion task. Parents' self-reported negative affect was assessed three times over the course of the study: baseline, after the anagram task, and after the cold pressor task. As expected, high-risk (compared to low-risk) parents reported higher levels of negative affect at each time point. Moreover, after completing the difficult anagram task, high-risk (compared to low-risk) parents exhibited higher pain sensitivity during the cold pressor task. Following completion of the cold pressor task, high-risk (compared to low-risk) parents exhibited greater accessibility of aggression-related schemata. Collectively, these findings indicate that under certain conditions, high-risk parents experience a confluence of aggression-related risk factors (i.e., negative affect, pain sensitivity, and aggression-related information processes) that may predispose them to aggressive behavior.

  15. 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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  17. The relationship between caregiver sensitivity and infant pain behaviors across the first year of life.

    PubMed

    Pillai Riddell, Rebecca; Campbell, Lauren; Flora, David B; Racine, Nicole; Din Osmun, Laila; Garfield, Hartley; Greenberg, Saul

    2011-12-01

    Recent research has begun to examine discrete caregiver pain management behaviors in the infant immunization context. However, there is a dearth of research exploring more global caregiving constructs, such as emotional availability, which can be used to examine the overall sensitivity of caregiver pain management. The aim of the present study was to examine the relationships between caregiver sensitivity (emotional availability) and infant pain behavior (baseline, immediately post-needle, 1 min after needle) over the first year of life. Parents and infants were a part of a Canadian longitudinal cohort (the Opportunities to Understand Childhood Hurt or OUCH cohort) followed up during their 2-, 4-, 6-, and 12-month immunizations (current n=731). Both within-age group analyses and over-age analyses were performed. Results indicated that: (1) over age, previous infant pain behavior predicts future infant pain behavior, but this varied depending on timing of pain response and age of infant; (2) over age, previous caregiver sensitivity strongly predicts future caregiver sensitivity; and (3) the concurrent relationship between caregiver sensitivity and every type of infant pain response is only consistently seen at the 12-month immunization. Caregiver sensitivity to the infant in pain is predicted most reliably from previous caregiver sensitivity, not infant pain behaviour. The significant concurrent relationship between caregiver sensitivity and infant pain behaviours is not seen until 12 months, replicating patterns in the infant development literature regarding the time at which the attachment relationship between parent and child can be reliably measured. Discussion addresses implications for both researchers and clinicians who work with infants in pain. PMID:22000098

  18. 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.

  19. 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

  20. 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

  1. Sensitivity and sensitisation in relation to pain severity in knee osteoarthritis: trait or state?

    PubMed Central

    Neogi, Tuhina; Frey-Law, Laura; Scholz, Joachim; Niu, Jingbo; Arendt-Nielsen, Lars; Woolf, Clifford; Nevitt, Michael; Bradley, Laurence; Felson, David T; Kvien, Tore K

    2014-01-01

    Objectives It is not clear whether heightened pain sensitivity in knee osteoarthritis (OA) is related to sensitisation induced by nociceptive input from OA pathology (‘state’) versus other confounding factors. Conversely, some individuals may be predisposed to sensitisation irrespective of OA (‘trait’). Methods The Multicenter Osteoarthritis Study is a longitudinal cohort of persons with or at risk of knee OA. We obtained knee X-rays, pain questionnaires and comprehensive assessment of factors that can influence pain sensitivity. We examined the relation of sensitisation and sensitivity assessed by mechanical temporal summation (TS) and pressure pain thresholds (PPTs) to knee OA and knee pain severity. To test whether sensitisation and sensitivity is a ‘state’ induced by OA pathology, we examined the relation of PPT and TS to knee OA duration and severity. Results In 2126 subjects (mean age 68, mean body mass index (BMI) 31, 61% female), PPT and TS were not associated with radiographic OA (ORs 0.9–1.0 for PPT and TS; p>0.05). However, PPT and TS were associated with pain severity (ORs: 1.7–2.0 for PPT; 1.3–1.6 for TS; p<0.05). Knee OA duration and radiographic severity were not associated with PPT or TS. Conclusions PPT and TS were associated with OA-related pain, but not radiographic OA after accounting for pertinent confounders in this large cohort. Lack of association with disease duration suggests at least some sensitisation and pain sensitivity may be a trait rather than state. Understanding the relationship between pathological pain and pain sensitivity/sensitisation offers insight into OA pain risk factors and pain management opportunities. PMID:24351516

  2. 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

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

    PubMed

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

    2015-05-01

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

  4. An experimental study of shared sensitivity to physical pain and social rejection.

    PubMed

    Eisenberger, Naomi I; Jarcho, Johanna M; Lieberman, Matthew D; Naliboff, Bruce D

    2006-12-15

    Recent evidence points to a possible overlap in the neural systems underlying the distressing experience that accompanies physical pain and social rejection (Eisenberger et al., 2003). The present study tested two hypotheses that stem from this suggested overlap, namely: (1) that baseline sensitivity to physical pain will predict sensitivity to social rejection and (2) that experiences that heighten social distress will heighten sensitivity to physical pain as well. In the current study, participants' baseline cutaneous heat pain unpleasantness thresholds were assessed prior to the completion of a task that manipulated feelings of social distress. During this task, participants played a virtual ball-tossing game, allegedly with two other individuals, in which they were either continuously included (social inclusion condition) or they were left out of the game by either never being included or by being overtly excluded (social rejection conditions). At the end of the game, three pain stimuli were delivered and participants rated the unpleasantness of each. Results indicated that greater baseline sensitivity to pain (lower pain unpleasantness thresholds) was associated with greater self-reported social distress in response to the social rejection conditions. Additionally, for those in the social rejection conditions, greater reports of social distress were associated with greater reports of pain unpleasantness to the thermal stimuli delivered at the end of the game. These results provide additional support for the hypothesis that pain distress and social distress share neurocognitive substrates. Implications for clinical populations are discussed. PMID:16890354

  5. 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

  6. 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

  7. 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

  8. Single vs composite measures of pain intensity: relative sensitivity for detecting treatment effects.

    PubMed

    Jensen, Mark P; Hu, Xiaojun; Potts, Susan L; Gould, Errol M

    2013-04-01

    Assay sensitivity remains a significant issue in pain clinical trials. One possible method for increasing assay sensitivity for detecting changes in pain intensity is to increase the reliability of pain intensity assessment by increasing the number of intensity ratings obtained, and combining these ratings into composite scores. The current study performed secondary analyses from a published clinical trial to test this possibility. The reliability and assay sensitivity pain intensity scores made up of 1 to 9 24-hour pain intensity recall ratings were compared. Although the reliability of the outcome measures improved as the number of items increased, this increase in reliability was not associated with an increase in assay sensitivity. A single 24-hour recall rating was about as valid (sensitive) for detecting treatment effects as composite scores made up of 2 to 9 different ratings. If this finding replicates in other pain populations, it has significant implications for the design and conduct of pain clinical trials. Specifically, it suggests the possibility that assessment burden (and associated costs and problems related to missing data) might be greatly reduced by specifying a single recall rating as the primary outcome variable. Research is needed to explore this possibility further.

  9. Anger regulation style, anger arousal and acute pain sensitivity: evidence for an endogenous opioid "triggering" model.

    PubMed

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

    2014-08-01

    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.

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

    PubMed Central

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

    2014-01-01

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

  11. 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

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

    PubMed Central

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

    2015-01-01

    Abstract A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-α and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes. PMID:26058036

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

    PubMed

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

    2015-10-01

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

  14. 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

  15. Central Sensitization in Functional Chronic Pain Syndromes: Overview and Clinical Application.

    PubMed

    Bettini, Liz; Moore, Ki

    2016-10-01

    The purpose of this review and clinical application article is to offer nurses up-to-date knowledge on peripheral and central sensitization in chronic functional pain syndromes, and to discuss therapies that have shown efficacy in treating various aspects of these disorders. Central sensitization is a result of changes in the peripheral and central nervous system due to noxious stimuli, such as illness or trauma. Once these changes occur, treatment for the associated syndromes requires a multimodal approach that includes behavioral pain psychology, physical therapy, and pharmacological agents that specifically target neuroinflammation, pain modulation, and amplification of pain pathways. More research needs to be conducted on the basis and patient perception of functional pain syndromes to reduce the morbidity and significant disability associated with these illnesses. Nurses have the opportunity to be at the forefront of this research because of their holistic and multidimensional approach to patient care, assessment, and symptom management. PMID:27553129

  16. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-04-01

    We aimed to evaluate the effect of painful tooth stimulation on gingival somatosensory sensitivity of healthy volunteers in a randomized, controlled design. Thirteen healthy volunteers (six women, seven men; 28.4 ± 5.0 years) were included for two experimental sessions of electrical tooth stimulation: painful tooth stimulation and tooth stimulation below the sensory threshold (control). Eight of the human subjects participated in a third session without tooth stimulation. In all sessions, the somatosensory sensitivity of the gingiva adjacent to the stimulated tooth was evaluated with a standardized battery of quantitative sensory tests (QST) before, immediately after and 30 min after tooth stimulation. Painful tooth stimulation evoked significant decreases in warmth and heat pain thresholds (P < 0.001) as well as pressure pain thresholds (increased sensitivity) (P = 0.024) and increases in mechanical detection thresholds (decreased sensitivity) (P < 0.050). Similar thermal threshold changes (P < 0.019) but no mechanical changes were found after tooth stimulation below the sensory threshold (P > 0.086). No QST changes were detected in the session without tooth stimulation (P > 0.060). In conclusion, modest increased gingival sensitivity to warmth, painful heat and pressure stimuli as well as desensitization to non-painful mechanical stimulation were demonstrated after tooth stimulation. This suggests involvement of competing heterotopic facilitatory and inhibitory mechanisms. Furthermore, stimulation below the sensory threshold induced similar thermal sensitization suggesting the possibility of activation of axon-reflex-like mechanisms even at intensities below the perception threshold. These findings may have implications for interpretation of somatosensory results in patients with chronic intraoral pain. PMID:25567087

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

    PubMed

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

    2015-04-01

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

  1. [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.

  2. [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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Epidermal adrenergic signaling contributes to inflammation and pain sensitization in a rat model of complex regional pain syndrome.

    PubMed

    Li, Wenwu; Shi, Xiaoyou; Wang, Liping; Guo, Tianzhi; Wei, Tzuping; Cheng, Kejun; Rice, Kenner C; Kingery, Wade S; Clark, J David

    2013-08-01

    In many patients, the sympathetic nervous system supports pain and other features of complex regional pain syndrome (CRPS). Accumulating evidence suggests that interleukin (IL)-6 also plays a role in CRPS, and that catecholamines stimulate production of IL-6 in several tissues. We hypothesized that norepinephrine acting through specific adrenergic receptors expressed on keratinocytes stimulates the production of IL-6 and leads to nociceptive sensitization in a rat tibial fracture/cast model of CRPS. Our approach involved catecholamine depletion using 6-hydroxydopamine or, alternatively, guanethidine, to explore sympathetic contributions. Both agents substantially reduced nociceptive sensitization and selectively reduced the production of IL-6 in skin. Antagonism of IL-6 signaling using TB-2-081 also reduced sensitization in this model. Experiments using a rat keratinocyte cell line demonstrated relatively high levels of β2-adrenergic receptor (β2-AR) expression. Stimulation of this receptor greatly enhanced IL-6 expression when compared to the expression of IL-1β, tumor necrosis factor (TNF)-α, or nerve growth factor. Stimulation of the cells also promoted phosphorylation of the mitogen-activated protein kinases P38, extracellular signal-regulated kinase, and c-Jun amino-terminal kinase. Based on these in vitro results, we returned to animal testing and observed that the selective β2-AR antagonist butoxamine reduced nociceptive sensitization in the CRPS model, and that local injection of the selective β2-AR agonist terbutaline resulted in mechanical allodynia and the production of IL-6 in the cells of the skin. No increases in IL-1β, TNF-α, or nerve growth factor levels were seen, however. These data suggest that in CRPS, norepinephrine released from sympathetic nerve terminals stimulates β2-ARs expressed on epidermal keratinocytes, resulting in local IL-6 production, and ultimately, pain sensitization.

  7. [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

  8. The effect of topical local anesthetics on thermal pain sensitivity in patients with irritable bowel syndrome.

    PubMed

    Rodrigues, Anthony; King, Christopher D; Wong, Fong; Riley, Joseph L; Schmidt, Siegfried; Mauderli, Andre P

    2012-01-01

    Generalized hypersensitivity that extends into somatic areas is common in patients with irritable bowel syndrome (IBS). The sensitized state, particularly assessed by experimental methods, is known to persist even during remissions of clinical pain. It was hypothesized that disease-related nociceptive activity in the gut maintains a systemic-sensitized state. The present study evaluated responses to prolonged thermal stimuli maintained at constant temperature or constant pain intensity during stimulation. The effect of topically applied rectal lidocaine on heat sensitivity was also evaluated. The question is whether silencing potential intestinal neural activity (which may not always lead to a conscious pain experience) with lidocaine attenuates sensitization of somatic areas. Tests were also performed where lidocaine was applied orally to control for systemic or placebo effects of the drug. The IBS subjects exhibited a greater sensitivity to somatic heat stimuli compared to controls; however, lidocaine had no discernible effect on sensitization in this sample of IBS patients, where most of the individuals did not have clinical pain on the day of testing.

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

    PubMed

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

    2016-02-01

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

  10. 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.

  11. 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

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

    PubMed

    White, Hillary D; Robinson, Thomas D

    2015-08-01

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

  13. 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

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

    PubMed Central

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

    2010-01-01

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

  15. P2X3 antagonists: novel therapeutics for afferent sensitization and chronic pain.

    PubMed

    Ford, Anthony P

    2012-05-01

    SUMMARY Despite decades of innovation and effort, the pharmaceutical needs of countless patients with chronic pain remain underserved. Effective and safe treatments must clearly come from novel approaches, yet targets and molecules selected hitherto have returned little benefit. Antagonism of P2X3 purinoceptors on pain-conveying nerves is a highly novel approach, and compounds from this class are advancing into patient studies. P2X3 channels are found in C- and Aδ-primary afferent neurons in most tissues, and are strikingly specific to pain detection. P2X3 antagonists block peripheral activation of these fibers via ATP, released from most cells by inflammation, injury, stress and distension, and clearly provide an alternative pharmacological mechanism to attenuate pain signals. P2X3 is also expressed presynaptically at central spinal terminals of afferent neurons, where ATP further sensitizes painful signals en route to the brain. The selectivity of P2X3 expression allows hope of a lower potential for adverse effects in brain, gut and cardiovascular tissues - limiting factors for most analgesics. P2X3 receptor-mediated sensitization has been implicated in rodent models in inflammatory, visceral, neuropathic and cancer pain states, as well as in airways hyper-reactivity, migraine and visceral organ irritability. Although we are often reminded that the effects of new medicines can translate poorly into clinical effectiveness, the broad efficacy seen following P2X3 inhibition in rodent models strengthens the prospect that an unprecedented mechanism to counter sensitization of afferent pathways may offer some merciful relief to millions of patients struggling daily with persistent discomfort and pain.

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

    PubMed

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

    2013-05-01

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

  17. 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

  18. A non-elaborative mental stance and decoupling of executive and pain-related cortices predicts low pain sensitivity in Zen meditators.

    PubMed

    Grant, Joshua A; Courtemanche, Jérôme; Rainville, Pierre

    2011-01-01

    Concepts originating from ancient Eastern texts are now being explored scientifically, leading to new insights into mind/brain function. Meditative practice, often viewed as an emotion regulation strategy, has been associated with pain reduction, low pain sensitivity, chronic pain improvement, and thickness of pain-related cortices. Zen meditation is unlike previously studied emotion regulation techniques; more akin to 'no appraisal' than 'reappraisal'. This implies the cognitive evaluation of pain may be involved in the pain-related effects observed in meditators. Using functional magnetic resonance imaging and a thermal pain paradigm we show that practitioners of Zen, compared to controls, reduce activity in executive, evaluative and emotion areas during pain (prefrontal cortex, amygdala, hippocampus). Meditators with the most experience showed the largest activation reductions. Simultaneously, meditators more robustly activated primary pain processing regions (anterior cingulate cortex, thalamus, insula). Importantly, the lower pain sensitivity in meditators was strongly predicted by reductions in functional connectivity between executive and pain-related cortices. Results suggest a functional decoupling of the cognitive-evaluative and sensory-discriminative dimensions of pain, possibly allowing practitioners to view painful stimuli more neutrally. The activation pattern is remarkably consistent with the mindset described in Zen and the notion of mindfulness. Our findings contrast and challenge current concepts of pain and emotion regulation and cognitive control; commonly thought to manifest through increased activation of frontal executive areas. We suggest it is possible to self-regulate in a more 'passive' manner, by reducing higher-order evaluative processes, as demonstrated here by the disengagement of anterior brain systems in meditators.

  19. 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.

  20. Investigating the effect of anxiety sensitivity, gender and negative interpretative bias on the perception of chest pain.

    PubMed

    Keogh, Edmund; Hamid, Rayhana; Hamid, Shahid; Ellery, Deborah

    2004-09-01

    Research suggests that anxiety sensitivity may be an important component in the negative response to pain sensations, especially those with cardiopulmonary origin. Furthermore, there is experimental evidence to suggest that such effects may be stronger in women than men. The primary aim of the current investigation was to determine the relative roles that anxiety sensitivity and gender have on the pain reports of patients referred to a hospital clinic with chest pain. A total of 78 female and 76 male adults were recruited on entry to a Rapid Access Medical Clinic. All patients had been referred with chest pain, and were administered a range of pain and anxiety measures prior to diagnosis. Results indicate that males were more likely to receive a diagnosis of cardiac chest pain, whereas females were more likely to receive a diagnosis of non-cardiac chest pain. Additionally, anxiety sensitivity was related to pain in women but not men. Finally, evidence was found for the mediating effect of negative interpretative bias on the relationship between anxiety sensitivity and pain. However, this mediating effect was only found in women. These results not only confirm that anxiety sensitivity is related to greater negative pain responses in women, but that this may be due to an increased tendency to negatively interpret sensations.

  1. 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

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

    PubMed Central

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

    2015-01-01

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

  3. Effect of Estrogen Depletion on Pain Sensitivity in Aromatase Inhibitor-Treated Women with Early-Stage Breast Cancer

    PubMed Central

    Henry, N. Lynn; Conlon, Anna; Kidwell, Kelley M.; Griffith, Kent; Smerage, Jeffrey B.; Schott, Anne F.; Hayes, Daniel F.; Williams, David A.; Clauw, Daniel J.; Harte, Steven E.

    2014-01-01

    Aromatase inhibitors (AI), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms (AIMSS) occur in approximately half of treated women, and lead to treatment discontinuation in 20–30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain, as well as with impairment of descending pain inhibitory pathways, which may be a risk factor for developing chronic pain. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AIMSS. Fifty postmenopausal breast cancer patients underwent pressure pain testing and conditioned pain modulation (CPM) assessment prior to AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed patients demonstrated impaired CPM, which was greater in those who had previously received chemotherapy (p=0.006). No statistically significant change in pressure pain threshold or CPM was identified following estrogen deprivation. In addition, there was no association with either measure of pain sensitivity and change in patient-reported pain with AI therapy. AIMSS are not likely due to decreased pain threshold or impaired CPM prior to treatment initiation, or to effects of estrogen depletion on pain sensitivity. Clinicaltrials.gov NCT01814397. Perspective This article presents our findings of the effect of estrogen deprivation on objective measures of pain sensitivity. In postmenopausal women, medication-induced estrogen depletion did not result in an identifiable change in pressure pain threshold or conditioned pain modulation. Impaired conditioned pain modulation may be associated with chemotherapy. PMID:24462504

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

    PubMed

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

    2012-06-01

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

  5. Distinct susceptibility to inoculated melanoma and sensitivity to cancer pain in mouse lines with high and low sensitivity to stress.

    PubMed

    Sacharczuk, Mariusz; Ragan, Agnieszka R; Szymanska, Hanna; Lesniak, Anna; Sadowski, Bogdan; Lipkowski, Andrzej W

    2012-01-01

    Approximately 30 years ago, we developed 2 mouse lines with enhanced and decreased opioid system activity using bidirectional selection for high (high analgesia [HA] line) and low (low analgesia [LA] line) swim stress-induced analgesia. These mouse lines differ substantially in pain sensitivity, measured as hind paw withdrawal latency in a hot plate test. Moreover, compared with the LA mice, the HA mice exhibited reduced energy expenditure under stress and different depression-like behavior as well as higher sensitivity to mutagens and the high frequency of spontaneous and carcinogen-induced tumors. In the current study, we observed distinct differences in the growth rate of orthotopically implanted melanoma and the onset of cancer pain. Whereas the HA line was prone to tumors and carcinogenesis was rapid in all specimens, the LA mice either did not develop tumors (70%) or developed tumors that often regressed spontaneously (30%). Animals from both lines developed robust thermal hypersensitivity in the tumor-bearing paw compared with animals that were injected with saline. However, we found that hyperalgesia in tumor-bearing mice persists for a much shorter time in the HA than in LA mice. Naltrexone, given subcutaneously, restored hyperalgesia in the HA mice, whereas it was ineffective in the LA mice. The results suggest that activity of the opioid system may influence carcinogenesis and the intensity of cancer pain and indicates that HA and LA mice are good models for such studies. PMID:23216641

  6. 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

  7. Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions

    PubMed Central

    Chen, Amanda L.-C.; Chen, Thomas J.H.; Waite, Roger L.; Reinking, Jeffrey; Tung, Howard L.; Rhoades, Patrick; Downs, B. William; Braverman, Eric; Braverman, Dasha; Kerner, Mallory; Blum, Seth H.; DiNubile, Nicholas; Smith, David; Oscar-Berman, Marlene; Prihoda, Thomas J.; Floyd, John B.; O’Brien, David; Liu, H.H.; Blum, Kenneth

    2014-01-01

    SUMMARY While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes. PMID:18951726

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

    PubMed

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

    2015-08-01

    The current study evaluated age differences in conditioned pain modulation using a test stimulus that provided the opportunity to evaluate changes in heat pain sensitivity, sensitization, and desensitization within the same paradigm. During this psychophysical test, pain intensity clamping uses REsponse Dependent STIMulation (REDSTIM) methodology to automatically adjust stimulus intensity to maintain a desired pain rating set-point. Specifically, stimulus intensity increases until a pre-defined pain rating (the setpoint) is exceeded, and then decreases until pain ratings fall below the setpoint, with continued increases and decreases dictated by ratings. The subjects are blinded in terms of the setpoint and stimulus intensities. Younger and older subjects completed two test sessions of two REDSTIM trials, with presentation of conditioning cold stimulation between the trials of one session but not the other. The results indicated that conditioning cold stimulation similarly decreased the overall sensitivity of younger and older subjects, as measured by the average temperature that maintained a setpoint rating of 20 (on a scale of 0-100). The conditioning stimulus also significantly enhanced sensitization following ascending stimulus progressions and desensitization following descending stimulus progressions in older subjects relative to younger subjects. Thus, older subjects experienced greater swings in sensitivity in response to varying levels of painful stimulation. These results are discussed in terms of control over pain intensity by descending central modulatory systems. These findings potentially shed new light on the central control over descending inhibition and facilitation of pain. PMID:25907744

  9. 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

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

    PubMed

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

    2010-06-01

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

  11. 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

  12. 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.

  13. 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

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

    PubMed Central

    2009-01-01

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

  15. 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.

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

    PubMed

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

    2016-10-01

    Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether γ-aminobutyric acid A (GABAA) receptors are involved in mediating the ethanol effects, muscimol, a selective GABAA receptor agonist, or bicuculline, a selective GABAA receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABAA receptors in the mPFC of rats. PMID:27628528

  17. 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

  18. Receiving of emotional signal of pain from conspecifics in laboratory rats.

    PubMed

    Nakashima, Satoshi F; Ukezono, Masatoshi; Nishida, Hiroshi; Sudo, Ryunosuke; Takano, Yuji

    2015-04-01

    Though recent studies have shown that rodents express emotions with their face, whether emotional expression in rodents has a communicative function between conspecifics is still unclear. Here, we demonstrate the ability of visual recognition of emotional expressions in laboratory rats. We found that Long-Evans rats avoid images of pain expressions of conspecifics but not those of neutral expressions. The results indicate that rats use visual emotional signals from conspecifics to adjust their behaviour in an environment to avoid a potentially dangerous place. Therefore, emotional expression in rodents, rather than just a mere 'expression' of emotional states, might have a communicative function. PMID:26064632

  19. 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

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

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

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

    PubMed Central

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

    2015-01-01

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

  7. Chest pain and high-sensitivity troponin: What is the evidence?

    PubMed

    Ashmore, Daniel

    2015-01-01

    The number of attendances and admissions of patients with chest pain to hospitals in England and Wales is increasing. Initial assessment may be unrewarding. Consequently, cardiac troponin has become the mainstay of investigation for non-ST-segment-elevation myocardial infarction and unstable angina, although only a small proportion of patients are eventually diagnosed as such. Current National Institute for Healthcare and Clinical Excellence guidance recommends measuring cardiac troponin levels on presentation and 10-12 h after onset of symptoms. A more effective diagnostic tool is needed. The aims are twofold: to increase accuracy of acute coronary syndrome diagnosis thus implementing the most appropriate management at an earlier stage while reducing costs and to provide a more rapid diagnosis to ease the anxieties of patients. Three key issues have been highlighted. The first is that many current studies do not have a 'normal/reference' population, making comparison between two studies difficult to interpret. Second, whether newer 'high-sensitivity' cardiac troponin tests can be used to rule out a myocardial infarction in a patient with chest pain is discussed. Third, whether a 'high-sensitivity' cardiac troponin has great enough specificity to differentiate between the number of other causes of raised troponin in a single test or whether serial testing is needed is assessed. A strategy for such serial testing is discussed. Finally, use of 'high-sensitivity' cardiac troponin in risk stratification of other disease processes is highlighted, which is likely to become common practice, changing the way we manage patients with, and without, chest pain. PMID:26770774

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

    PubMed

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

    2013-01-01

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

  9. Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT val(158)met polymorphism.

    PubMed

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

    2009-01-01

    Increased pain sensitivity after opioid administration (opioid-induced hyperalgesia) and/or repeated painful stimuli is an individually varying and clinically important phenomenon. The functional polymorphism (val(158)met) of the Catechol-O-methyltransferase (COMT) gene regulates the metabolism of dopamine/noradrenaline. Individuals homozygous for the met(158) allele have been reported to have increased pain sensitivity and there are findings of lower micro-opioid system activation during sustained pain. We hypothesized that met/met individuals would exhibit higher pain sensitization and opioid-induced hyperalgesia in response to repeated pain stimuli and an intravenous injection of an opioid drug. Participants were 43 healthy subjects who went through an experiment where five blocks of pain were induced to the hand using a heat probe. After each stimulus subjects rated the pain on a visual analogue scale (VAS) from 0 mm (no pain) to 100 mm (worst possible pain). Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug. At baseline there was no difference in pain ratings between the COMTval(158)met genotypes, F(2, 39)<1. However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval(158)met genotype, F(2, 36) = 4.17, p = 0.024. Met/met individuals reported significantly more pain compared to val/val, p = 0.010. A pairwise comparison of baseline and the opioid intervention demonstrated that analgesia was induced in all groups (p = 0.042) without a separating effect for genotype (n.s). We suggest that the initial response of the descending pain system is not influenced by the COMTval(158)met polymorphism but when the system is challenged the difference is revealed. An important clinical implication of this may be that the COMTval(158)met related differences may be more expressed in individuals where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients. This has to be

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

    PubMed

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

    2010-08-01

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

  11. 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

  12. 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

  13. 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

  14. 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.

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

    PubMed

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

    2014-01-01

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

  16. Pelvic organ cross-sensitization to enhance bladder and urethral pain behaviors in rats with experimental colitis.

    PubMed

    Yoshikawa, S; Kawamorita, N; Oguchi, T; Funahashi, Y; Tyagi, P; Chancellor, M B; Yoshimura, N

    2015-01-22

    Neural cross-sensitization has been postulated as a mechanism underlying overlaps of chronic pelvic pain disorders such as bladder pain syndrome/interstitial cystitis (BPS/IC) and irritable bowel syndrome (IBS). Animals with experimental colitis have been used to study the underlying mechanisms for overlapped pelvic pain symptoms, and shown to exhibit bladder overactivity evidenced by frequent voiding; however, it has not directly been evaluated whether pain sensation derived from the lower urinary tract is enhanced in colitis models. Also, the cross-sensitization between the colon and urethra has not been studied previously. In the present study, we therefore investigated pain behaviors induced by nociceptive stimuli in the lower urinary tract and the involvement of C-fiber afferent pathways using rats with colitis induced by intracolonic application of 2,4,6-trinitrobenzenesulfonic acid (TNBS). In TNBS-induced colitis rats at 10 days, intravesical application of resiniferatoxin (RTx) induced a significantly greater number of episodes of both licking and freezing behaviors, which were reduced by capsaicin-sensitive C-fiber afferent desensitization. Histochemical studies using fluorescent dye tracers injected into the colon, bladder or urethra showed that dichotomized afferent neurons comprised 6.9-14.5% of L1, L6 and S1 dorsal root ganglion (DRG) neurons innervating the colon or the lower urinary tract. Transient receptor potential vanilloid 1 (TRPV1) mRNA expression was significantly increased in, the bladder, urethra and S1 DRG in colitis rats. An increase in myeloperoxidase (MPO) activity was found in the colon, but not in the bladder or urethra after intracolonic TNBS treatment. These results indicate that TNBS-induced colitis increased pain sensitivity in the bladder and urethra via activation of C-fiber afferent pathways due to colon-to-bladder and colon-to-urethral cross-sensitization, suggesting the contribution of pelvic organ cross-sensitization

  17. Changes in pain and pressure pain sensitivity after manual treatment of active trigger points in patients with unilateral shoulder impingement: a case series.

    PubMed

    Hidalgo-Lozano, Amparo; Fernández-de-las-Peñas, César; Díaz-Rodríguez, Lourdes; González-Iglesias, Javier; Palacios-Ceña, Domingo; Arroyo-Morales, Manuel

    2011-10-01

    The aim of this case series was to investigate changes in pain and pressure pain sensitivity after manual treatment of active trigger points (TrPs) in the shoulder muscles in individuals with unilateral shoulder impingement. Twelve patients (7 men, 5 women, age: 25 ± 9 years) diagnosed with unilateral shoulder impingement attended 4 sessions for 2 weeks (2 sessions/week). They received TrP pressure release and neuromuscular interventions over each active TrP that was found. The outcome measures were pain during arm elevation (visual analogue scale, VAS) and pressure pain thresholds (PPT) over levator scapulae, supraspinatus infraspinatus, pectoralis major, and tibialis anterior muscles. Pain was captured pre-intervention and at a 1-month follow-up, whereas PPT were assessed pre- and post-treatment, and at a 1-month follow-up. Patients experienced a significant (P < 0.001) reduction in pain after treatment (mean ± SD: 1.3 ± 0.5) with a large effect size (d > 1). In addition, patients also experienced a significant increase in PPT immediate after the treatment (P < 0.05) and one month after discharge (P < 0.01), with effect sizes ranging from moderate (d = 0.4) to large (d > 1).A significant negative association (r(s) = -0.525; P = 0.049) between the increase in PPT over the supraspinatus muscle and the decrease in pain was found: the greater the decrease in pain, the greater the increase in PPT. This case series has shown that manual treatment of active muscle TrPs can help to reduce shoulder pain and pressure sensitivity in shoulder impingement. Current findings suggest that active TrPs in the shoulder musculature may contribute directly to shoulder complaint and sensitization in patients with shoulder impingement syndrome, although future randomized controlled trials are required.

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

    PubMed

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

    2015-09-01

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

  19. 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

  20. 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

  1. 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

    2016-08-30

    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.

  2. 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.

  3. 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

  4. 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

  5. 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.

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

    PubMed

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

    2014-07-01

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

  7. 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

  8. 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.

  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. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain

    PubMed Central

    Pan, Lin

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

  11. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain

    PubMed Central

    Pan, Lin

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats. PMID:27642352

  12. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

    PubMed

    Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats. PMID:27642352

  13. 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

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

    PubMed

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

    2016-01-01

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

  15. 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 ...

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

    PubMed Central

    Bablis, Peter; Pollard, Henry; Bonello, Rod

    2008-01-01

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

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

    PubMed

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

    2015-09-01

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

  18. 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

  19. Role of opioid system in modulation of pain sensitivity under conditons of low and high environmental temperature.

    PubMed

    Kolotilova, A B; Guzevatikh, L S; Valujskikh, D V; Emel'yanova, T G

    2008-06-01

    The dependence of pain sensitivity in acetic acid-induced writhing test on environmental temperature was described by a bell-shaped curve. The maximum number of writhings was observed in thermoneutral environment and minimum in hot and cold environment. Under conditions of opioid receptor blockade with naloxone, naltrindole, norbinaltorphimine, analgesia is partially mediated by micro-, delta-, and kappa-opioid receptors.

  20. 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

  1. 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

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

    PubMed Central

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

    2014-01-01

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

  3. Self-assessment of pain and discomfort in patients with temporomandibular disorders: a comparison of five different scales with respect to their precision and sensitivity as well as their capacity to register memory of pain and discomfort.

    PubMed

    Magnusson, T; List, T; Helkimo, M

    1995-08-01

    Five different scales of self-assessment of pain were tested in patients with temporomandibular disorders. The precision and sensitivity and the capacity to register memory of pain and discomfort were compared for each of the five scales. The behaviour rating scale was found to be superior to the other four scales in respect of precision and sensitivity to pain and discomfort and when recording the memory of these two variables. This scale was also considered by the patients to be the most relevant and the simplest to understand. From these results, the behaviour rating scale can be recommended when measuring pain and discomfort in patients with temporomandibular disorders.

  4. 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.

  5. 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

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

    PubMed

    Becker, Susanne; Kleinböhl, Dieter; Hölzl, Rupert

    2012-09-01

    Regarding awareness as a consistent concept has contributed to the controversy about implicit learning. The present study emphasized the importance of distinguishing aspects of awareness in order to determine whether learning is implicit. By decomposing awareness into awareness of contingencies, of the procedure being a learning task, and of the reinforcing stimuli, it was demonstrated that implicit operant learning modulated pain sensitivity. All of these aspects of awareness were demonstrated to not be necessary for learning. Additionally, discrimination of contingencies was not necessary on different levels of processing as demonstrated by a verbal and a behavioral method. It was demonstrated that explicit cognitive processes about one's own behavior, impaired learning, even though these cognitions were not immediately related to the learning process. The results of this study are of special interest in the context of pain, since implicit operant learning can explain the gradual development of hypersensitivity in chronic pain. PMID:22521471

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

    PubMed

    Becker, Susanne; Kleinböhl, Dieter; Hölzl, Rupert

    2012-09-01

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

  8. 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

  9. 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…

  10. 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

  11. 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 ...

  12. Central sensitivity syndromes: mounting pathophysiologic evidence to link fibromyalgia with other common chronic pain disorders.

    PubMed

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

    2011-03-01

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

  13. 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

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

    PubMed

    Hoffman, Donna

    2015-01-01

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

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

    PubMed

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

    2011-09-15

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  17. 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.

  18. 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

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

    PubMed Central

    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

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

    PubMed

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

    2015-01-01

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

  1. 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

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

    PubMed

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

    2014-04-01

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

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2009-01-28

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

  7. 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

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

    PubMed

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

    2015-10-01

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

  9. 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

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

    PubMed

    Yarushkina, N I; Filaretova, L P

    2015-01-01

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

  11. A computational model for sex-specific genetic architecture of complex traits in humans: Implications for mapping pain sensitivity

    PubMed Central

    Wang, Chenguang; Cheng, Yun; Liu, Tian; Li, Qin; Fillingim, Roger B; Wallace, Margaret R; Staud, Roland; Kaplan, Lee; Wu, Rongling

    2008-01-01

    Understanding differences in the genetic architecture of complex traits between the two sexes has significant implications for evolutionary studies and clinical diagnosis. However, our knowledge about sex-specific genetic architecture is limited largely because of a lack of analytical models that can detect and quantify the effects of sex on the complexity of quantitative genetic variation. Here, we derived a statistical model for mapping DNA sequence variants that contribute to sex-specific differences in allele frequencies, linkage disequilibria, and additive and dominance genetic effects due to haplotype diversity. This model allows a genome-wide search for functional haplotypes and the estimation and test of haplotype by sex interactions and sex-specific heritability. The model, validated by simulation studies, was used to detect sex-specific functional haplotypes that encode a pain sensitivity trait in humans. The model could have important implications for mapping complex trait genes and studying the detailed genetic architecture of sex-specific differences. PMID:18416828

  12. 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

  13. 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

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. 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.

  17. Genetic analysis of decreased praziquantel sensitivity in a laboratory strain of Schistosoma mansoni.

    PubMed

    Pica-Mattoccia, Livia; Doenhoff, Michael J; Valle, Cristiana; Basso, Annalisa; Troiani, Anna-Rita; Liberti, Piero; Festucci, Alfredo; Guidi, Alessandra; Cioli, Donato

    2009-07-01

    A laboratory strain of Schistosoma mansoni subjected to repeated in vivo praziquantel (PZQ) treatments for several generations has been previously found to have lesser sensitivity to the drug than the original unselected strain. In this study we have collected evidence on the mode of inheritance of the partial insensitivity exhibited by the PZQ-selected schistosomes. A single male and a single female worm of the two strains, assorted in the four possible combinations, were introduced into the mesenteric veins of mice and the eggs produced by each pair were used as the source of the F(1) progeny. PZQ sensitivity was assessed using both in vivo and in vitro methods. In the first approach, the PZQ ED(50) was determined by infecting mice with cercariae of the strains to be tested, treating at seven weeks with different drug doses and counting the number of surviving worms three weeks later. For the in vitro approach, adult schistosomes kept in culture were exposed overnight to different PZQ concentrations and their survival was monitored during the subsequent 7 days. Results from both approaches lead to the conclusion that hybrid schistosomes of the F(1) generation have a drug sensitivity intermediate between those of the two parental strains and are thus suggestive of a pattern of partial dominance for the trait under study. PMID:19426668

  18. 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.

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

    PubMed Central

    Noseda, Rodrigo; Burstein, Rami

    2013-01-01

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

  20. 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.

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

    PubMed

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

    2013-01-01

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

  2. 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

  3. 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.

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

    PubMed

    Etherton, Joseph L; Tapscott, Brian E

    2015-01-01

    Although chronic pain patients commonly report problems with concentration and memory, recent research indicates that induced pain alone causes little or no impairment on several Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests, suggesting that cognitive complaints in chronic pain may be attributable to factors other than pain. The current studies examined potential effects of induced pain on Wechsler Memory Scale-Fourth Edition (WMS-IV) visual working memory index (VWM) subtests (Experiment 1, n = 32) and on the immediate portions of WMS-IV auditory memory (IAM) subtests (Experiment 2, n = 55). In both studies, participants were administered one of two subtests (Symbol Span or Spatial Addition for Experiment 1; Logical Memory or Verbal Paired Associates for Experiment 2) normally and were then administered the alternate subtest while experiencing either cold pressor pain induction or a nonpainful control condition. Results indicate that induced pain in nonclinical volunteers did not impair performance on either VWM or IAM performance, suggesting that pain alone does not account for complaints or deficits in these domains in chronic pain patients. Nonpainful variables such as sleep deprivation or emotional disturbance may be responsible for reported cognitive complaints in chronic pain patients. PMID:25655774

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. Skeletal muscle contractility, self-reported pain and tissue sensitivity in females with neck/shoulder pain and upper Trapezius myofascial trigger points– a randomized intervention study

    PubMed Central

    2012-01-01

    Background In relation to Myofascial Triggerpoints (MFTrPs) of the upper Trapezius, this study explored muscle contractility characteristics, the occurrence of post-intervention muscle soreness and the effect of dry needling on muscle contractile characteristics and clinical outcomes. Methods Seventy-seven female office workers (25-46yrs) with and without neck/shoulder pain were observed with respect to self-reported pain (NRS-101), pressure-pain threshold (PPT), maximum voluntary contraction (Fmax) and rate of force development (RFD) at baseline (pre-intervention), immediately post-intervention and 48 hours post-intervention. Symptomatic and asymptomatic participant groups were each randomized into two treatment sub-groups (superficial (SDN) and deep dry needling (DDN)) after baseline testing. At 48 hours post-intervention participants were asked whether delayed onset muscle soreness (DOMS) and/or post-needling soreness had developed. Results Muscle contractile characteristics did not differ between groups at baseline. Forty-six individuals developed muscle soreness (39 from mechanical testing and seven from needling). No inter-group differences were observed post-intervention for Fmax or RFD for the four sub-groups. Over the observation period, symptomatic participants reported less pain from both SDN (p= 0.003) and DDN (p=0.011). However, PPT levels were reduced for all participants (p=0.029). Those reporting DOMS experienced significant decreases in PPT, irrespective of symptom state or intervention (p=0.001). Conclusions In selected female neck/shoulder pain sufferers, maximum voluntary contraction and rapid force generation of the upper Trapezius was not influenced by clinically relevant self-reported pain or the presence of diagnostically relevant MFTrPs. Dry needling, deep or superficial, did not affect measured functional outcomes over the 48-hour observation period. DOMS affected participants uniformly irrespective of pain, MFTrP status or intervention

  12. Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: a double-blind, placebo-controlled, cross-over study.

    PubMed

    Perrotta, Armando; Serrao, Mariano; Tassorelli, Cristina; Arce-Leal, Natalia; Guaschino, Elena; Sances, Grazia; Rossi, Paolo; Bartolo, Michelangelo; Pierelli, Francesco; Sandrini, Giorgio; Nappi, Giuseppe

    2011-05-01

    Nitric-oxide donor glyceryl-trinitrate (GTN) modulates cerebral and spinal regions that are involved in migraine and pain processing. We hypothesized that in migraineurs, the susceptibility to develop a migraine attack after GTN administration should parallel with an high sensitivity to GTN-induced change in the pain processing at spinal level. We used the temporal summation threshold (TST) of the lower limb nociceptive withdrawal reflex (NWR) and the related pain sensation to study in parallel the time-course of the effect of the GTN administration on the pain processing at spinal level in migraine and healthy subjects. Twenty-eight (21 F; 7M; mean age 34.2 ± 8.2) migraine and 15 (11 F; 4M; mean age 35.9 ± 8.9) healthy subjects were recruited in a double-blind, placebo-controlled, cross-over trial. Neurophysiological examinations were carried out before (baseline) and 30', 60', 120', 180' and 240' after GTN (0.9 mg sublingual) or placebo administration during two different sessions. In migraineurs, GTN administration was associated to a significant facilitation in temporal summation of pain (reduced TST and increased painful sensation) 60', 120' and 180' after drug intake when compared to baseline, to placebo condition and to controls after GTN intake. Furthermore, in migraineurs who developed migraine after GTN, a significant facilitation in temporal summation of pain was detected 60', 120' and 180' after drug intake when compared to patients without clinical response. In migraineurs the susceptibility to develop migraine attack after GTN administration seems to be a specific trait of a subgroup of patients linked to a supersensitivity of the pain system to GTN.

  13. 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

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

    PubMed Central

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

    2012-01-01

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

  15. 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

  16. 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 ...

  17. 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

  18. 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.

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

    PubMed

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

    2012-08-01

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

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

    PubMed

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

    2012-08-01

    Healthy children are often required to repeatedly undergo painful medical procedures (eg, immunizations). Although memory is often implicated in children's reactions to future pain, there is a dearth of research directly examining the relationship between the 2. The current study investigated the influence of children's memories for a novel pain stimulus on their subsequent pain experience. One hundred ten healthy children (60 boys) between the ages of 8 and 12 years completed a laboratory pain task and provided pain ratings. Two weeks later, children provided pain ratings based on their memories as well as their expectancies about future pain. One month following the initial laboratory visit, children again completed the pain task and provided pain ratings. Results showed that children's memory of pain intensity was a better predictor of subsequent pain reporting than their actual initial reporting of pain intensity, and mediated the relationship between initial and subsequent pain reporting. Children who had negatively estimated pain memories developed expectations of greater pain prior to a subsequent pain experience and showed greater increases in pain ratings over time than children who had accurate or positively estimated pain memories. These findings highlight the influence of pain memories on healthy children's expectations of future pain and subsequent pain experiences and extend predictive models of subsequent pain reporting. PMID:22560288

  1. 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

  2. Study of Cassini Radio Occultation Sensitivity to Atmospheric Constituents Based on New Laboratory Measurements

    NASA Astrophysics Data System (ADS)

    Steffes, P. G.; Mohammed, P. N.

    2002-09-01

    As described in an accompanying paper by Mohammed and Steffes (BAAS, DPS-02), new laboratory measurements of the 9 mm opacity of phosphine and ammonia under simulated conditions for Saturn have recently been completed. Using these results, plus previous results for the centimeter-wavelength opacity of these constituents (see, e.g., Hoffman et al. ICARUS 152, 172-184, 2001), studies of the sensitivity of the Cassini radio link to atmospheric constituents encountered during radio occultations are being conducted. Preliminary results suggest that for orbits with favorable occultation geometry, the Ka-Band (32 GHz, or 9.3 mm) downlink will encounter measurable absorption from PH3 at the 0.5 Bar pressure level, and will be capable of profiling phosphine down to altitudes with pressures up to 0.8 Bars, where the opacity from ammonia would then dominate followed by loss of signal (LOS) at about 0.9 Bars. As with the Voyager 2 radio occultation experiment, the X-Band (8.4 GHz, or 3.6 cm) downlink is expected to encounter measurable absorption at the 0.8 Bar pressure level from both PH3 and NH3, before losing the signal at the 1 Bar pressure level, and the S-Band (2.3 GHz or 13 cm) downlink is expected to encounter measurable absorption from both PH3 and NH3 at the 1.1 Bar pressure level with profiling capability down to the 1.6 Bar pressure level. A computer model to simulate the ray paths and attenuation encountered during Saturn occultations is currently under development. This work is supported by the NASA Planetary Atmospheres Program under grant NAG5-12122.

  3. Laboratory medicine as the science that underpins medicine: the "high-sensitivity" troponin paradigm.

    PubMed

    Ferraro, Simona; Panteghini, Mauro

    2015-04-01

    The availability of so-called high-sensitivity troponin assays (hsTn) has scored a compelling goal for laboratory medicine, allowing the safe clinical application of international recommendations for the definition of acute myocardial infarction (AMI). However, the introduction of hsTn has not been welcomed by clinicians, claiming an increase in false-positive results. Here we critically trace back the steps following the introduction of hsTn by referring to the 5-year practical experience in our academic hospital and to suitable information available in the literature. In agreement with published data, we found that hsTn introduction was associated with an increased number of AMI diagnoses, whereas the test volume, the revascularization rate, and the proportion of cases with negative angiography findings remained virtually unchanged. Fast-track protocols for ruling out AMI have been further optimized to recommend sampling at presentation and after 3 h only. We focus on a cost-effective use of hsTn that can account for all clinical variables increasing the pre-test probability in order to ensure that tests are ordered only for patients at medium to high risk for acute coronary syndrome (ACS). To guide interpretation of results, hsTn typical release patterns suggestive for AMI should be identified by evaluating the significance of concentration changes. hsTn have markedly shortened the time to rule out or rule in AMI and has the potential to improve the prognostic assessment of critical patients in clinical contexts different from ACS.

  4. 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.

  5. Effects of Soil Moisture on the Temperature Sensitivity of Soil Heterotrophic Respiration: A Laboratory Incubation Study

    PubMed Central

    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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

    Sharmin Ani, Nushrat; Chakraborty, Sudip

    2016-01-01

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

  8. 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

  9. 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

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

    PubMed

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

    2015-03-20

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

  11. 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.

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

    PubMed Central

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

    2015-01-01

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

  13. The effect of meloxicam on pain sensitivity, rumination time, and clinical signs in dairy cows with endotoxin-induced clinical mastitis.

    PubMed

    Fitzpatrick, C E; Chapinal, N; Petersson-Wolfe, C S; DeVries, T J; Kelton, D F; Duffield, T F; Leslie, K E

    2013-05-01

    The objectives of this study were to (1) evaluate the use of a pressure algometer and an automated rumination monitoring system to assess changes in pain sensitivity and rumination time in response to endotoxin-induced clinical mastitis and (2) evaluate the effect of the nonsteroidal antiinflammatory drug meloxicam on pain sensitivity and rumination time, as well as other clinical signs, in dairy cattle with endotoxin-induced clinical mastitis. Clinical mastitis was induced in 12 primiparous and 12 multiparous lactating dairy cows by intramammary infusion of 25 µg of Escherichia coli lipopolysaccharide (LPS) into 1 uninfected quarter. Immediately after, half the cows were injected subcutaneously with meloxicam (treated group) and half with the same volume of a placebo solution (control group). Pain sensitivity was assessed by measuring the difference in pressure required to elicit a response on the control and challenged quarter using an algometer 3 d before, immediately before, and at 3, 6, 12, and 24h after LPS infusion and either meloxicam or placebo injection. Rumination was continuously monitored from 2 d before to 3 d after LPS infusion using rumination loggers. Udder edema, body temperature, somatic cell score, and dry matter intake were also monitored to evaluate the occurrence and the duration of the inflammation after LPS infusion. In control animals, the difference in the pressure applied to the control and challenged quarters (control - challenged quarter) increased by 1.1 ± 0.4 kg of force 6h after LPS infusion compared with the baseline, suggesting an increase in pain sensitivity in the challenged quarter. Neither the LPS infusion nor the meloxicam treatment had an effect on daily rumination time. However, the rumination diurnal pattern on the day of LPS infusion showed an overall deviation from the baseline pattern. Cows spent less time ruminating in the hours following LPS infusion and more time ruminating later in the day. Meloxicam did not alter

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

    PubMed

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

    2016-04-01

    Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity. PMID:26802474

  15. Spinal pain.

    PubMed

    Izzo, R; Popolizio, T; D'Aprile, P; Muto, M

    2015-05-01

    The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic pain, much more difficult to treat. The clinical assessment of pain source can be a challenge because of the complex anatomy and function of the spine; the advanced imaging methods are often not sufficient for a definitive diagnosis because similar findings could be present in either asymptomatic and symptomatic subjects: a clinical correlation is always mandatory and the therapy cannot rely uniquely upon any imaging abnormalities. Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally

  16. Basic aspects of musculoskeletal pain: from acute to chronic pain

    PubMed Central

    Arendt-Nielsen, Lars; Fernández-de-las-Peñas, César; Graven-Nielsen, Thomas

    2011-01-01

    The transition from acute to chronic musculoskeletal pain is not well understood. To understand this transition, it is important to know how peripheral and central sensitization are manifested and how they can be assessed. A variety of human pain biomarkers have been developed to quantify localized and widespread musculoskeletal pain. In addition, human surrogate models may be used to induce sensitization in otherwise healthy volunteers. Pain can arise from different musculoskeletal structures (e.g. muscles, joints, ligaments, or tendons), and differentiating the origin of pain from those different structures is a challenge. Tissue specific pain biomarkers can be used to tease these different aspects. Chronic musculoskeletal pain patients in general show signs of local/central sensitization and spread of pain to degrees which correlate to pain intensity and duration. From a management perspective, it is therefore highly important to reduce pain intensity and try to minimize the duration of pain. PMID:23115471

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  18. Different sensitivity of pain-related chemosensory potentials evoked by stimulation with CO2, tooth pulp event-related potentials, and acoustic event-related potentials to the tranquilizer diazepam.

    PubMed

    Thürauf, N; Ditterich, W; Kobal, G

    1994-12-01

    1. The aim of this study was to investigate the sensitivity of pain-related potentials used in experimental pain models to the non-specific effects of the tranquilizer diazepam. Pain-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 and after painful stimulation of the tooth pulp. Acoustically evoked potentials were measured in order to compare their sensitivity to the tranquilizer diazepam with the sensitivity of the pain-related potentials. 2. Twenty volunteers participated in this randomised, double-blind, three-fold crossover study. Measurements were obtained before and 20 min after the administration of the drug. Event-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 (two stimulus intensities: 60% v/v and 70% v/v CO2), after painful stimulation of the tooth pulp (two stimulus intensities: 2.2 x and 3.3 x detection threshold), and after non-painful acoustical stimulation of the right ear. The subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale. In addition the spontaneous EEG was analysed in the frequency domain and the vigilance of the subjects was assessed in a tracking task. 3. Diazepam reduced significantly the amplitudes of the event-related potentials after painful stimulation of the tooth pulp and after acoustical stimulation. In contrast only a small, statistically non-significant reduction could be found after painful stimulation with CO2. The pain ratings of the painful stimuli were not affected by diazepam. Diazepam reduced the performance of the tracking task. A decrease of arousal could be found in the alpha 2-range, whereas in the beta 2 and the theta-range the power density increased under diazepam. 4. We demonstrated that event-related potentials after painful stimulation of the nasal mucosa with CO2 are less affected by the nonspecific effects of the tranquilizer diazepam than event-related potentials after painful

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

    SciTech Connect

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

    2010-09-17

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

  20. 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

  1. Neonatal pain.

    PubMed

    Walker, Suellen M

    2014-01-01

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

  2. 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…

  3. A family-based investigation of cold pain tolerance.

    PubMed

    Birklein, F; Depmeier, C; Rolke, R; Hansen, C; Rautenstrauss, B; Prawitt, D; Magerl, W

    2008-08-15

    In the present study the question was addressed whether sensitivity to experimental pain stimuli differs between families, which are previously characterized by the degree of cold tolerance (very insensitive or very sensitive) of one family member. A total of 232 healthy medical students were screened for cold pain tolerance employing a cold pressor test. Subsequently 50 of them were investigated in detail under laboratory conditions. The water temperature was 1 degrees C, the maximum time in water 3 min, cold pain was rated on a 101 step numerical rating scale every 10s. Two of the most cold pain sensitive (shortest time in ice water) and insensitive (lowest ratings) students were selected and as many as possible of their family members were recruited. In all of them cold pressor test, pinprick pain threshold, pressure pain threshold, skin temperature, hospital anxiety and depression scale and COMT val158met polymorphism (with the exception of three individuals) were assessed. Analysis (ANOVA) revealed that the cold pressor results of the students predicted the mean ratings (p<0.04) and the time in ice water (p<0.03) of their own families. Furthermore, pinprick pain threshold (p<0.002) and to a lesser extent pressure pain thresholds (p<0.03) were significantly related to cold pain tolerance. The other variables, including the COMT polymorphism, were not related to cold pain tolerance in our study. In conclusion our results suggest that cold pain tolerance may be at least partially inherited. Genetic or environmental factors might explain family clustering of cold pain sensitivity.

  4. 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.

  5. 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

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

    PubMed Central

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

    2015-01-01

    Objective Spinal Cord Stimulation (SCS) has become a widely used treatment option for a variety of pain conditions. Substantial variability exists in the degree of benefit obtained from SCS and patient selection is a topic of expanding interest and importance. However, few studies have examined the potential benefits of dynamic Quantitative Sensory Testing (QST) to develop objective measures of SCS outcomes or as a predictive tool to help patient selection. Psychological characteristics have been shown to play an important role in shaping individual differences in the pain experience and may aid in predicting responses to SCS. Static laboratory pain-induction measures have also been examined in their capacity for predicting SCS outcomes. Methods The current study evaluated clinical, psychological and laboratory pain measures at baseline, during trial SCS lead placement, as well as one month and three months following permanent SCS implantation in chronic pain patients who received SCS treatment. Several QST measures were conducted, with specific focus on examination of dynamic models (central sensitization and conditioned pain modulation [CPM]) and their association with pain outcomes three months post SCS implantation. Results Results suggest few changes in QST over time. However, central sensitization and CPM at baseline were significantly associated with clinical pain at three months following SCS implantation, controlling for psycho/behavioral factors and pain at baseline. Specifically, enhanced central sensitization and reduced CPM were associated with less self-reported pain three months following SCS implantation. Conclusions These findings suggest a potentially important role for dynamic pain assessment in individuals undergoing SCS, and hint at potential mechanisms through which SCS may impart its benefit. PMID:25800088

  7. Kinetics of drug action in disease states. XLI. Effect of adrenalectomy on the hypnotic activity of phenobarbital, the neurotoxicity of theophylline and pain sensitivity in rats.

    PubMed

    Hoffman, A; Levy, G

    1993-02-01

    The purpose of this investigation was to determine the effects of adrenalectomy and adrenalectomy with corticosterone replacement on pain sensitivity and on the pharmacodynamics of a central nervous system depressant, phenobarbital, and a central nervous system stimulant, theophylline. Male Sprague-Dawley rats, bilaterally adrenalectomized, were maintained on normal saline solution or normal saline solution with corticosterone, 160 micrograms/ml, as drinking water for 9 or 11 days. Sham-operated animals served as normal controls. They were then tested for pain sensitivity by the tail-flick method. Phenobarbital or theophylline was infused i.v. slowly until the onset of loss of righting reflex or of maximal seizures, respectively. Samples of cerebrospinal fluid (CSF), blood (for serum) and the brain were obtained at that time and assayed for phenobarbital or theophylline by high-performance liquid chromatography. Compared to the controls, the adrenalectomized rats required a smaller dose and lower concentrations of phenobarbital in serum, brain and CSF (12% decrease) to produce loss of righting reflex. The opposite effect was observed in adrenalectomized rats supplemented with corticosterone. Adrenalectomy had no apparent effect on the dose and the serum, brain and CSF concentrations of theophylline at the onset of maximal seizures whereas adrenalectomized, corticosterone-supplemented animals required a larger dose and higher concentrations (17% increase in CSF) of theophylline than controls to produce seizures. Tail-flick latency was slightly (19%) but statistically significantly reduced in adrenalectomized rats and lengthened (18%) in adrenalectomized, corticosterone-supplemented animals.

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

    PubMed

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

    2006-09-01

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

  9. 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 ...

  10. 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

  11. 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

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

    Andrew, David

    2009-05-01

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

  14. [Laboratory procedures in adenoviruses. II. Sensitivity of various cell cultures as determined by endpoint titration (author's transl)].

    PubMed

    Wigand, R; Schulz, R

    1975-01-01

    The sensitivity of human embryonic kidney (HEK), human amnion (HAm) and HeLa cells for human adenoviruses was investigated by means of endpoint titrations of 13 prototype strains and numerous original specimens from patients. Prototypes and original specimens showed the same behavior. Adenoviruses of subgrouppp III produced nearly identical titers in all 3 cell cultures, while for subgroup I HAm cells showed a 10- to 100-fold lower titer. On the other hand, HAm cells are nearly as sensitive as HEK cells for type 8, whereas HeLa cells are less sensitive. For other viruses of subgroup II and for subgrou IV, HAm (for type 12 also HeLa) cells are less sensitive than HEK cells. Out of three HeLa cell strains tested the Bristol strain was inferior to the other two in its sensitivity. Concerning the speed of the CPE development, HEK cells are superior for all types, the difference being greatest for subgroup I towards HAm and HeLa and for type 8 towards HeLa cells. The length of incubation necessary for the appearance of CPE even with minimal amounts of virus is 40 days for type 8 in all kinds of cell cultures, whereas for adenoviruses of sub-groups I and III, which are predominantly isolated in the routine laboratory, 25 days for HEK and 30 days for HAm and HeLa cells may suffice in most cases. When endpoint titrations are compared with titers obtained by immunofluorescence, it appears that this technique may be applied as a screening method; thus long incubation periods of negative specimens can be saved. The amounts of infectious virus present in original specimens are reported; the highest quantity was found in specimens containing subgroup I viruses.

  15. A rapid and sensitive culture test for the laboratory diagnosis of genital herpes in women.

    PubMed Central

    Darougar, S; Walpita, P; Thaker, U; Goh, B T; Dunlop, E M

    1986-01-01

    A rapid and sensitive cell culture test has been developed to detect herpes simplex virus (HSV) in women with genital herpes. The virus is cultured by inoculation and centrifugation of cell monolayers, and the virus inclusions are detected using an indirect immunofluorescence test. The test takes only 48 hours to complete compared with the conventional cell culture test, which may take up to eight days. Of a total of 2100 cervical specimens collected from unselected women attending a sexually transmitted diseases (STD) clinic and inoculated in parallel, HSV was isolated from 55 specimens by either or both tests. Of these 55 positive specimens, 54(98%) were positive by the rapid test but only 24(44%) by the conventional test (McNemars test; p less than 0.001). Images PMID:3013758

  16. Sex and gender differences in pain and analgesia.

    PubMed

    Mogil, Jeffrey S; Bailey, Andrea L

    2010-01-01

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

  17. 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

  18. The effect of spinally administered WIN 55,212-2, a cannabinoid agonist, on thermal pain sensitivity in diabetic rats

    PubMed Central

    Jahanabadi, Samane; Hadian, Mohamad Reza; Shamsaee, Javad; Tavangar, Seyed Mohammad; Abdollahi, Alireza; Dehpour, Ahmadreza; Mehr, Shahram Ejtemaei

    2016-01-01

    Objective(s): Diabetic neuropathy (DN) is a common complication of diabetes that leads to allodynia, impaired nerve conduction, and progressive sensory loss. The aim of this study was to observe the effect of a high-affinity cannabinoid receptors agonist, WIN 55,212-2, on thermal hyperalgesia, nerve conduction velocity and sciatic nerve histopathology in diabetic rats. Materials and Methods: Diabetes was induced in rats using a single dose of streptozotocin (45 mg/kg IP). Results: Intrathecal (IT) administration of WIN55, 212-2 (1, 10, 100 µg/10 µl, IT), produced antinociceptive effects in the hot plate test and also improved nerve conduction velocity (100 µg/10 µl, IT) and sciatic nerve histology. Conclusion: These data show that cannabinoids have potent antinociceptive effects through direct actions in the spinal dorsal horn of nociceptive pathway. This suggests that intrathecally administered cannabinoids may offer hopeful strategies for the treatment of diabetic neuropathic pain. PMID:27279983

  19. Hypothalamic and thalamic sites of action of interleukin-1 beta on food intake, body temperature and pain sensitivity in the rat.

    PubMed

    Sellami, S; de Beaurepaire, R

    1995-10-01

    Interleukin-1beta (IL-1beta ) has anorectic, hyperthermic, and analgesic or hyperalgesic (depending on the studies) effects in the rat. These effects appear to be mediated by the central nervous system; however, the exact localization of action of IL-1beta in the brain has never been delineated with precision. The purpose of this study was to determine precisely where IL- IO acts in the hypothalamus and in the thalamus to modulate food intake, body temperature, and pain sensitivity. Animals were tested after local intracerebral microinjections of 5 ng of IL-1beta dissolved in 0.3 microl of saline, or of 0.3 microl saline alone. The results show that IL-1beta has anorectic effects in 3 diencephalic sites (the perifornical area, an area above the optic chiasma, and an area internal to the mamillo-thalamic tract), and not in 9 other sites tested. IL-1beta has hyperthermic effects in 7 sites (the media] and lateral preoptic area, the hypothalamic periventricular substance, the dorso-medial and arcuate nuclei of the hypothalamus, and the centro-medial and gelatinosus nuclei of the thalamus), and not in 6 other sites. IL-1beta has analgesic effects in the centro-medial and gelatinosus nuclei of the thalamus, and not in 7 other sites. IL-1beta also increases food intake and decreases pain sensation thresholds in the paraventricular nucleus of the hypothalamus. Therefore IL-1beta has very selective anatomical sites of action in the brain, and the paraventricular nucleus of the hypothalamus appears to have special properties regarding the effects of IL-1beta on food intake and pain sensation regulation.

  20. Self-sustaining smoldering combustion for NAPL remediation: laboratory evaluation of process sensitivity to key parameters.

    PubMed

    Pironi, Paolo; Switzer, Christine; Gerhard, Jason I; Rein, Guillermo; Torero, Jose L

    2011-04-01

    Smoldering combustion has been introduced recently as a potential remediation strategy for soil contaminated by nonaqueous phase liquids (NAPLs). Published proof-of-concept experiments demonstrated that the process can be self-sustaining (i.e., requires energy input only to start the process) and achieve essentially complete remediation of the contaminated soil. Those initial experiments indicated that the process may be applicable across a broad range of NAPLs and soils. This work presents the results of a series of bench-scale experiments that examine in detail the sensitivity of the process to a range of key parameters, including contaminant concentration, water saturation, soil type, and air flow rates for two contaminants, coal tar and crude oil. Smoldering combustion was observed to be self-sustaining in the range 28,400 to 142,000 mg/kg for coal tar and in the range 31,200 to 104,000 mg/kg for crude oil, for the base case air flux. The process remained self-sustaining and achieved effective remediation across a range of initial water concentrations (0 to 177,000 mg/kg water) despite extended ignition times and decreased temperatures and velocities of the reaction front. The process also exhibited self-sustaining and effective remediation behavior across a range of fine to coarse sand grain sizes up to a threshold maximum value between 6 mm and 10 mm. Propagation velocity is observed to be highly dependent on air flux, and smoldering was observed to be self-sustaining down to an air Darcy flux of at least 0.5 cm/s for both contaminants. The extent of remediation in these cases was determined to be at least 99.5% and 99.9% for crude oil and coal tar, respectively. Moreover, no physical evidence of contamination was detected in the treatment zone for any case where a self-sustaining reaction was achieved. Lateral heat losses to the external environment were observed to significantly affect the smoldering process at the bench scale, suggesting that the field

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

    PubMed

    Goodin, Burel R; Bulls, Hailey W

    2013-05-01

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

  2. Genetic Evidence for Involvement of Neuronally Expressed S1P1 Receptor in Nociceptor Sensitization and Inflammatory Pain

    PubMed Central

    Mair, Norbert; Benetti, Camilla; Andratsch, Manfred; Leitner, Michael G.; Constantin, Cristina E.; Camprubí-Robles, Maria; Quarta, Serena; Biasio, Wolfgang; Kuner, Rohini; Gibbins, Ian L.; Kress, Michaela; Haberberger, Rainer V.

    2011-01-01

    Sphingosine-1-phosphate (S1P) is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P1 receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P1 receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P1 receptor. Our data show that neuronally expressed S1P1 receptors play a significant role in regulating nociceptor function and that S1P/S1P1 signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation. PMID:21359147

  3. 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

  4. 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 ...

  5. Abdominal pain

    MedlinePlus

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

  6. Heel pain

    MedlinePlus

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

  7. 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

  8. [Painful neuropathies and small fiber involvement].

    PubMed

    Lefaucheur, J-P

    2014-12-01

    It is customary to consider that a purely sensory and painful neuropathy accompanied by normal electroneuromyographic examination may be or must be a small fiber neuropathy. This leads to perform specific tests, such as measuring the intra-epidermal nerve fiber density on skin biopsy or neurophysiological tests, such as evoked potentials to noxious stimuli (laser) or quantification of thermal sensory thresholds. However, these tests are only sensitive to the loss of small fibers (A-delta and C), which does not reflect the mechanisms responsible for peripheral neuropathic pain. Selective loss of small sensory fibers inherently generates a sensory deficit that does not necessarily present a painful character. Also, assigning the cause of a painful neuropathy to a small fiber neuropathy has no pathophysiological sense, although there are indirect links between these two conditions. In fact, it is not possible to explain univocally peripheral neuropathic pain, which reflects complex and diverse mechanisms, involving different types of nerve fibers. In this context, the clinical and laboratory approach must be improved to better understand the underlying mechanisms. It is imperative to interpret the data provided by laboratory tests and to correlate these data to the clinical signs and symptoms presented by the patients. Thus, one must go beyond many a priori and misinterpretations that unfortunately exist in this area at present and are not based on any solid pathophysiological basis.

  9. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels.

    PubMed

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick

    2013-08-01

    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors. PMID:23685008

  10. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels.

    PubMed

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick

    2013-08-01

    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors.

  11. 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

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

    PubMed

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

    2014-05-01

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

  13. 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

  14. 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.

  15. 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

  16. 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 ...

  17. Chest pain

    MedlinePlus

    ... provider may ask questions such as: Is the pain between the shoulder blades? Under the breast bone? Does the pain ... How long does the pain last? Does the pain go from your chest into your shoulder, arm, neck, jaw, or back? Is the pain ...

  18. 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

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. Ankle pain

    MedlinePlus

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

  3. Foot pain

    MedlinePlus

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

  4. 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, ...

  5. Knee pain

    MedlinePlus

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

  6. 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 ...

  7. Leg pain

    MedlinePlus

    Pain - leg; Aches - leg; Cramps - leg ... Leg pain can be due to a muscle cramp (also called a charley horse ). Common causes of ... a long time An injury can also cause leg pain from: A torn or overstretched muscle ( strain ) ...

  8. 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…

  9. Patellofemoral pain.

    PubMed

    Crossley, Kay M; Callaghan, Michael J; van Linschoten, Robbart

    2016-02-01

    Patellofemoral pain refers to pain behind or around the patella (also known as patellofemoral pain syndrome, anterior knee pain, runner's knee, and, formerly, chondromalacia patellae). Patellofemoral pain is common, accounting for 11-17% of all knee pain presentations to general practice.(1 2) While it typically occurs in physically active people aged <40 years, it also affects people of all activity levels and ages.(1 2) Patellofemoral pain can be diagnosed in the clinic, and evidence based treatments can reduce pain and improve function, allowing patients to maintain a physically active lifestyle. PMID:26834209

  10. Basic science of pain.

    PubMed

    DeLeo, Joyce A

    2006-04-01

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

  11. Combined analysis of circulating β-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects

    PubMed Central

    2013-01-01

    Background Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the μ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide β-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls. Results The plasma β-endorphin levels were significantly higher in controls than in pain patients. A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found. Conclusions Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids. PMID:23402298

  12. [Mechanisms of myofascial pain].

    PubMed

    Boureau, F; Delorme, T; Doubrère, J F

    2000-01-01

    The aim of this paper is to review available data and current hypotheses concerning myofascial pain syndrome pathophysiology and implications for clinical practice. A muscular hypothesis has been proposed for episodic and chronic tension headache as well as for myofascial syndrome and fibromyalgia. These different syndromes may be compared as, besides their frequent combination, they have common features characterized by spontaneous pain, painful points, and lack of objective findings. They must be distinguished because each has its own diagnostic criteria. Pressure algometry appears to be a reliable method for assessing pressure sensitivity in myofascial pain. Pressure pain is not specific to tension headache and can be observed in other chronic headaches. It has not been demonstrated that the trigger points of fibromyalgia are specific in idiopathic cases. It is difficult to find an electrophysiological investigation which is specific for myofascial pain. For daily practice, the clinical approach with interview and examination remain the advisable attitude. Pathophysiological hypotheses help in better understanding of referred pain by sensitization of nociceptive central pathways according to the Ruch convergence projection theory (1965), modified by Mense in 1994. These theories do not however provide an explanation of the primary muscular mechanisms. Implications for myofascial pain patient management is discussed. PMID:11139741

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

    PubMed Central

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

    2016-01-01

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

  14. 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

  15. 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)

  16. 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 ...

  17. Shoulder pain

    MedlinePlus

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

  18. 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 ...

  19. Behavioral Inhibition Sensitivity and Emotional Response Suppression: A Laboratory Test Among Adolescents in a Fear-Relevant Paradigm

    ERIC Educational Resources Information Center

    Leen-Feldner, Ellen W.; Zvolensky, Michael J.; Feldner, Matthew T.

    2004-01-01

    This study examined behavioral inhibition sensitivity and emotional suppression in a fear-relevant slide-viewing paradigm among adolescents (n = 95). After controlling for state anxiety, behavioral inhibition sensitivity significantly predicted subjective anxiety and the valence and control dimensions of emotional responding but was not associated…

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

    NASA Astrophysics Data System (ADS)

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

    1988-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Autism Spectrum Disorder and Amplified Pain

    PubMed Central

    2015-01-01

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

  3. The influence of experimental pain intensity in the local and referred pain area on somatosensory perception in the area of referred pain.

    PubMed

    Kosek, Eva; Hansson, Per

    2002-01-01

    The aim of this study was to investigate the influence of experimental pain intensity in the local and referred pain area on somatosensory perception thresholds in the area of referred pain. Pain was induced by intramuscular electrical stimulation of the left infraspinatus muscle in 12 healthy individuals. The stimulation corresponded to the local pain threshold ("mild local pain"), the referred pain threshold ("mild referred pain"), and a pain intensity corresponding to 2 on a 10-point category scale in the referred pain area ("moderate referred pain"). Quantitative sensory testing was performed to assess perception thresholds in the referred pain area and the homologous contralateral area before and during stimulation. Perception thresholds to light touch (LTTs), pressure pain (PPTs), and to innocuous as well as noxious warmth and cold were assessed. During stimulation the LTTs increased in the referred pain area compared to baseline, uninfluenced by pain intensity. Perception thresholds to innocuous cold and warmth increased bilaterally during the stimulation, without relation to pain intensity. Heat pain thresholds were not affected. Compared to baseline, PPTs increased bilaterally during stimulation corresponding to "mild local pain" and "mild referred pain", respectively, and a further increase was seen during "moderate referred pain". The decreased sensitivity to innocuous cold, warmth, and pressure pain was bilateral, indicating activation of endogenous net inhibitory mechanisms interacting bilaterally. We found no influence of pain intensity on somatosensory thresholds restricted to the referred pain area and light touch was the only affected modality in the referred pain area only.

  4. Back Pain

    MedlinePlus

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

  5. [Oral pain].

    PubMed

    Benslama, Lotfi

    2002-02-15

    Pain, a major symptom of stomatological disease, usually leads to a specialist consultation. Most commonly it is caused by dental caries and differs in nature and in intensity according to the stage of disease: dentinitis, pulpitis, desmodontitis and dental abscess. Added to this is peridental pain and the pre- and post-operative pains related to these diseases. Almost all oral-maxillary pathology is painful, be it boney such as in osteomyelitis and fractures, mucosal in gingivo-stomatitis and aphthous ulcers, or tumourous. However, besides the "multidisciplinary" facial pains such as facial neuralgia and vascular pain, two pain syndromes are specific to stomatology: pain of the tempero-mandibular joint associated with problems of the bite and glossodynia, a very common somatic expression of psychological problems.

  6. Pain Management

    MedlinePlus

    ... the brain played a role in producing the perception of pain. In the 19th century, physician-scientists ... they are experiencing. Discoveries of differences in pain perceptions and responses to treatment by gender has have ...

  7. Finger pain

    MedlinePlus

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

  8. Pain Assessment

    MedlinePlus

    ... as a result of the pain, and the nature of other medical and psychiatric problems, should be ... information helps the health care provider understand the nature of the pain or the potential benefits of ...

  9. Breast pain

    MedlinePlus

    Pain - breast; Mastalgia; Mastodynia; Breast tenderness ... There are many possible causes for breast pain. For example, hormone level changes from menstruation or pregnancy often cause breast tenderness. Some swelling and tenderness just before your period ...

  10. Patellofemoral Pain.

    PubMed

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

    2016-02-01

    Patellofemoral pain is characterized by insidious onset anterior knee pain that is exaggerated under conditions of increased patellofemoral joint stress. A variety of risk factors may contribute to the development of patellofemoral pain. It is critical that the history and physical examination elucidate those risk factors specific to an individual in order to prescribe an appropriate and customized treatment plan. This article aims to review the epidemiology, risk factors, diagnosis, and management of patellofemoral pain. PMID:26616176

  11. Patellofemoral Pain.

    PubMed

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

    2016-02-01

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

  12. Pain: A Distributed Brain Information Network?

    PubMed Central

    Mano, Hiroaki; Seymour, Ben

    2015-01-01

    Understanding how pain is processed in the brain has been an enduring puzzle, because there doesn't appear to be a single “pain cortex” that directly codes the subjective perception of pain. An emerging concept is that, instead, pain might emerge from the coordinated activity of an integrated brain network. In support of this view, Woo and colleagues present evidence that distinct brain networks support the subjective changes in pain that result from nociceptive input and self-directed cognitive modulation. This evidence for the sensitivity of distinct neural subsystems to different aspects of pain opens up the way to more formal computational network theories of pain. PMID:25562782

  13. Pain control.

    PubMed

    Boey, W K

    1991-01-01

    There are two components to the perception of pain; the 'sensory' and the 'reactive'. Psychological factors control the latter. Pain research is rapidly advancing: the discovery of endorphins and opioid receptors, the appreciation of the psychological component of pain and the multidisciplinary approach to chronic pain are major advances. Pain can be classified as acute or chronic. Acute pain is easy to diagnose, the cause of pain obvious and the treatment logical, chronic pain has a greater psychological component, is difficult to diagnose and treatment is often empirical. Methods of pain control include drugs, injection techniques, electro stimulation, non invasive therapies, denervation procedures and palliative procedures. A multidisciplinary approach and a combination of methods is necessary to treat chronic pain. Spinal opioids, radiofrequency thermocoagulation, intrapleural bupivacaine, cryoanalgesia and patient controlled analgesia are recent advances in pain control. However, most pain can be controlled adequately with simple methods; what is essential is the interest and commitment of the physician towards achieving optimum therapeutics. PMID:1674199

  14. Chronic pain.

    PubMed

    Russo, C M; Brose, W G

    1998-01-01

    Chronic pain is an emotional experience and is defined as pain lasting greater than six months. It is important to understand the neurophysiology of pain in order to treat it. Nociceptors in the periphery travel to the substantia gelatinosa of the spinal cord while secondary and tertiary afferents transmit information from the dorsal horn to the brain. Modification of pain information may take place in these ascending pathways or in descending pathways. Treatment of chronic pain is most successful when it is approached in a multidisciplinary fashion with the focus not only on treatment of underlying etiology, but also on the secondary impacts of pain on the patient's life. The management of chronic pain requires special expertise. Most of the experts in chronic pain assessment and management organize themselves into pain treatment centers. These centers vary widely in their approach to the problem. The most sophisticated is a multidisciplinary center that is university-based and includes teaching and research. Treatment of chronic pain includes a variety of medications, psychological support, and rehabilitation. Multidisciplinary pain management is also an integral part of the palliative care and hospice concept used to treat cancer pain.

  15. Temporomandibular pain

    PubMed Central

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

    2016-01-01

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

  16. Temporomandibular pain

    PubMed Central

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

    2016-01-01

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

  17. Temporomandibular pain.

    PubMed

    Prasad, S Raghavendra; Kumar, N Ravi; Shruthi, H R; Kalavathi, S D

    2016-01-01

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

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

    PubMed

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

    2015-04-01

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

  19. Identifying the Most Sensitive and Specific Sign and Symptom Combinations for Cholera: Results from an Analysis of Laboratory-Based Surveillance Data from Haiti, 2012–2013

    PubMed Central

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

    2015-01-01

    Since October 2010, over 700,000 cholera cases have been reported in Haiti. We used data from laboratory-based surveillance for diarrhea in Haiti to evaluate the sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the cholera case definitions recommended by the World Health Organization (WHO). From April 2012 to May 2013, we tested 1,878 samples from hospitalized patients with acute watery diarrhea; 1,178 (62.7%) yielded Vibrio cholerae O1. The sensitivity and specificity of the WHO case definition for cholera in an epidemic setting were 91.3% and 43.1%, respectively, and the PPV and NPV were 72.8% and 74.8%, respectively. The WHO case definition for cholera in an area where cholera is not known to be present had lower sensitivity (63.1%) and NPV (55.1%) but higher specificity (74.2%) and PPV (80.0%). When laboratory diagnostic testing is not immediately available, clinicians can evaluate signs and symptoms to more accurately identify cholera patients. PMID:25732682

  20. [Neural basis of pain].

    PubMed

    Calvino, Bernard

    2006-03-01

    Main elements concerning the physiology of pain are described, as well as the structures of the nervous system at the origin of the central control of pain: peripheral fibres (small diameter myelinated A delta and unmyelinated C fibres); spinal ascending pathways; cerebral structures relaying nociceptive information (medial and ventro-postero-lateral thalamic relays); SI and SII cortical areas; spinal segmentary and supraspinal excitatory and inhibitory controls; diffuse noxious inhibitory controls (DNIC). Chronic pain is a result of two processes: peripheral and central sensitization, in relation with inflammation and nerve injury at peripheral level and with neuroplasticity at central level. Neurotrophins, mainly NGF and BDNF and their receptors (LNTR, TrkA and TrkB) are involved in these processes. Pain is a result of an unpleasant emotional experience: its various components, mainly the emotional one, may be increased or decreased considering the different characteristics of the stimulus and of the affective state of the patient, as well as the context in which this stimulus is applied. The role of physiological systems, unconnected with those classically involved in the physiology of nociception and pain, such as the motor cortex in phantom limb pain, are described in conclusion, to focus on the extreme complexity of the control systems of pain in humans. PMID:16556514

  1. Pharmacogenomics in pain treatment.

    PubMed

    Peiró, Ana M; Planelles, Beatriz; Juhasz, Gabriella; Bagdy, György; Libert, Frédéric; Eschalier, Alain; Busserolles, Jérôme; Sperlagh, Beata; Llerena, Adrián

    2016-09-01

    The experience of chronic pain is one of the commonest reasons for seeking medical attention, being a major issue in clinical practice. While pain is a universal experience, only a small proportion of people who felt pain develop pain syndromes. In addition, painkillers are associated with wide inter-individual variability in the analgesic response. This may be partly explained by the presence of single nucleotide polymorphisms in genes encoding molecular entities involved in pharmacodynamics and pharmacokinetics. However, uptake of this information has been slow due in large part to the lack of robust evidences demonstrating clinical utility. Furthermore, novel therapies, including targeting of epigenetic changes and gene therapy-based approaches are further broadening future options for the treatment of chronic pain. The aim of this article is to review the evidences behind pharmacogenetics (PGx) to individualize therapy (boosting the efficacy and minimizing potential toxicity) and genes implicated in pain medicine, in two parts: (i) genetic variability with pain sensitivity and analgesic response; and (ii) pharmacological concepts applied on PGx. PMID:27662648

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

    PubMed Central

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

    2016-01-01

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

  3. Relationship Between Shoulder Pain and Kinetic and Temporal-Spatial Variability In Wheelchair Users

    PubMed Central

    Rice, Ian M; Jayaraman, Chandrasekaran; Hsiao-Wecksler, Elizabeth T.; Sosnoff, Jacob J.

    2014-01-01

    Objective To examine intra-individual variability of kinetic and temporal-spatial parameters of wheelchair propulsion as a function of shoulder pain in manual wheelchair users (MWU). Design Cohort Setting University Research Laboratory Participants 26 adults with physical disabilities who use a manual wheelchair for mobility full time (>80% ambulation) Interventions Participants propelled their own wheelchairs with force sensing wheels at a steady state pace on a dynamometer at 3 speeds (self-selected, 0.7m/s, 1.1m/s) for 3 minutes. Temporal-spatial and kinetic data were recorded unilaterally at the hand rim. Main Outcome Measures Shoulder pain was quantified with the wheelchair users shoulder pain index (WUSPI). Intra-individual mean, standard deviation (SD), and coefficient of variation of (CV = mean/SD) with kinetic and temporal spatial metrics were determined at the handrim. Results There were no differences in mean kinetic and temporal spatial metrics as a function of pain group (p's > 0.016). However, individuals with pain displayed less relative variability (CV) in peak resultant force and push time then pain free individuals (p<0.016). Conclusions Shoulder pain had no influence on mean kinetic and temporal-spatial propulsion variables at the handrim however group differences were found in relative variability. These results suggest that intra-individual variability analysis is sensitive to pain. It is proposed that variability analysis may offer an approach of earlier identification of manual wheelchair users at risk for developing shoulder pain. PMID:24291595

  4. Pain and Inflammatory Bowel Disease

    PubMed Central

    Bielefeldt, Klaus; Davis, Brian; Binion, David G.

    2010-01-01

    Abdominal pain is a common symptom of inflammatory bowel disease (IBD: Crohn’s disease, ulcerative colitis). Pain may arise from different mechanisms, which can include partial blockage and gut distention as well as severe intestinal inflammation. A majority of patients suffering from acute flares of IBD will experience pain, which will typically improve as disease activity decreases. However, a significant percentage of IBD patients continue experiencing symptoms of pain despite resolving inflammation and achieving what appears to be clinical remission. Current evidence suggests that sensory pathways sensitize during inflammation, leading to persistent changes in afferent neurons and central nervous system pain processing. Such persistent pain is not only a simple result of sensory input. Pain processing and even the activation of sensory pathways is modulated by arousal, emotion, and cognitive factors. Considering the high prevalence of iatrogenic as well as essential neuropsychiatric comorbidities including anxiety and depression in IBD patients, these central modulating factors may significantly contribute to the clinical manifestation of chronic pain. The improved understanding of peripheral and central pain mechanisms is leading to new treatment strategies that view pain as a biopsychosocial problem. Thus, improving the underlying inflammation, decreasing the excitability of sensitized afferent pathways, and altering emotional and/or cognitive functions may be required to more effectively address the difficult and disabling disease manifestations. PMID:19130619

  5. Gender role expectations of pain is associated with pain tolerance limit but not with pain threshold.

    PubMed

    Defrin, Ruth; Shramm, Libby; Eli, Ilana

    2009-09-01

    Gender role expectations of pain (GREP) was suggested to predict sex differences in pain perception. Our aim was to explore sex differences in GREP and investigate its relationship with heat-pain threshold (HPT) and heat-pain tolerance limit (HPTL). University students (115 males, 134 females) filled the GREP questionnaire. HPT and HPTL were measured in a sample of 72 students. Additionally, GREP values of the present sample were compared with those of the original, American sample to explore possible cultural effects. Both males and females perceive themselves (and their own sex in general) to be less sensitive to pain and less willing to report of pain than the opposite sex. Males perceived themselves and other men, to endure pain relatively similar to women whereas females perceived themselves and other women as less endurable to pain than men. HPT was similar for the two sexes but males had higher HPTL than females. Within each sex, HPTL correlated mainly with self's perception of pain sensitivity. The American and Israeli samples differed in that Israeli males and females presented stronger stereotypical views towards same and opposite sexes. Both males and females held stereotypical "macho" attitude towards themselves with regard to pain sensitivity and willingness to report of pain however only females held stereotypical, "macho" attitude towards themselves with regard to pain endurance. The sex differences in GREP and in HPTL and the correlations between GREP items and experimental thresholds suggest that the relationship between GREP and experimental pain is complex and sex-specific. It also appears that GREP is affected by culture.

  6. Somatosensory nociceptive characteristics differentiate subgroups in people with chronic low back pain: a cluster analysis.

    PubMed

    Rabey, Martin; Slater, Helen; OʼSullivan, Peter; Beales, Darren; Smith, Anne

    2015-10-01

    The objectives of this study were to explore the existence of subgroups in a cohort with chronic low back pain (n = 294) based on the results of multimodal sensory testing and profile subgroups on demographic, psychological, lifestyle, and general health factors. Bedside (2-point discrimination, brush, vibration and pinprick perception, temporal summation on repeated monofilament stimulation) and laboratory (mechanical detection threshold, pressure, heat and cold pain thresholds, conditioned pain modulation) sensory testing were examined at wrist and lumbar sites. Data were entered into principal component analysis, and 5 component scores were entered into latent class analysis. Three clusters, with different sensory characteristics, were derived. Cluster 1 (31.9%) was characterised by average to high temperature and pressure pain sensitivity. Cluster 2 (52.0%) was characterised by average to high pressure pain sensitivity. Cluster 3 (16.0%) was characterised by low temperature and pressure pain sensitivity. Temporal summation occurred significantly more frequently in cluster 1. Subgroups were profiled on pain intensity, disability, depression, anxiety, stress, life events, fear avoidance, catastrophizing, perception of the low back region, comorbidities, body mass index, multiple pain sites, sleep, and activity levels. Clusters 1 and 2 had a significantly greater proportion of female participants and higher depression and sleep disturbance scores than cluster 3. The proportion of participants undertaking <300 minutes per week of moderate activity was significantly greater in cluster 1 than in clusters 2 and 3. Low back pain, therefore, does not appear to be homogeneous. Pain mechanisms relating to presentations of each subgroup were postulated. Future research may investigate prognoses and interventions tailored towards these subgroups. PMID:26020225

  7. Somatosensory nociceptive characteristics differentiate subgroups in people with chronic low back pain: a cluster analysis.

    PubMed

    Rabey, Martin; Slater, Helen; OʼSullivan, Peter; Beales, Darren; Smith, Anne

    2015-10-01

    The objectives of this study were to explore the existence of subgroups in a cohort with chronic low back pain (n = 294) based on the results of multimodal sensory testing and profile subgroups on demographic, psychological, lifestyle, and general health factors. Bedside (2-point discrimination, brush, vibration and pinprick perception, temporal summation on repeated monofilament stimulation) and laboratory (mechanical detection threshold, pressure, heat and cold pain thresholds, conditioned pain modulation) sensory testing were examined at wrist and lumbar sites. Data were entered into principal component analysis, and 5 component scores were entered into latent class analysis. Three clusters, with different sensory characteristics, were derived. Cluster 1 (31.9%) was characterised by average to high temperature and pressure pain sensitivity. Cluster 2 (52.0%) was characterised by average to high pressure pain sensitivity. Cluster 3 (16.0%) was characterised by low temperature and pressure pain sensitivity. Temporal summation occurred significantly more frequently in cluster 1. Subgroups were profiled on pain intensity, disability, depression, anxiety, stress, life events, fear avoidance, catastrophizing, perception of the low back region, comorbidities, body mass index, multiple pain sites, sleep, and activity levels. Clusters 1 and 2 had a significantly greater proportion of female participants and higher depression and sleep disturbance scores than cluster 3. The proportion of participants undertaking <300 minutes per week of moderate activity was significantly greater in cluster 1 than in clusters 2 and 3. Low back pain, therefore, does not appear to be homogeneous. Pain mechanisms relating to presentations of each subgroup were postulated. Future research may investigate prognoses and interventions tailored towards these subgroups.

  8. Non-Cardiac Chest Pain

    MedlinePlus

    ... been termed “Esophageal or visceral hypersensitivity” (enhanced esophageal perception or sensitivity to balloon distension). Although the cause ... can be used to improve this exaggerated pain perception. Non-esophageal Causes of NCCP NCCP is a ...

  9. Chronic pain in the workplace.

    PubMed

    Faucett, Julia; McCarthy, Dolores

    2003-09-01

    Chronic pain, especially chronic back pain, is costly to workers, their families, employers, and society. Successful return to productive work life for the worker with chronic pain requires multi-disciplinary efforts, including those of the nurse case manager, occupational health nurse, and nursing specialist in pain management. Sensitivity to the dynamics of multiple stakeholders in the RTW process is essential because of their diverse perspectives. Successful RTW can be facilitated by a combination of approaches, including case management, worker capacity evaluation, ergonomic job analysis, team design of job modifications, appropriate medical treatment, and self management by the worker.

  10. Does Cytological Laboratory Holds the Responsibility for the Low Sensitivity of the PAP Test in Detecting Endometrial Cancer?

    PubMed

    Milicić, Valerija; Matić, Tereza Solocki; Martinek, Vjenceslav; Tomasković, Igor; Ramljak, Vesna

    2015-09-01

    Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer

  11. Complex regional pain syndrome.

    PubMed

    Sebastin, Sandeep J

    2011-05-01

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

  12. Complex regional pain syndrome

    PubMed Central

    Sebastin, Sandeep J

    2011-01-01

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

  13. [Frequency of isolation and antibiotic sensitivity of strains of coli bacilli from urinary tract infections isolated in private laboratories].

    PubMed

    Bourlioux, P; Bourlioux, N; Bournaud, M

    1983-06-01

    Frequency of isolation and antibiotic susceptibility of E. coli strains isolated from urinary tract infections in private laboratory. The urinary tract infections are not the most frequent infections in man. However cytobacteriological analysis are often required for the diagnosis. The critical evaluation of 3000 analysis brings the followed conclusions: 1) 16% of the analysis correspond to a urinary tract infection; 2) the most frequently isolated germs are E. coli (65%) and Proteus mirabilis (11%); 3) E. coli is always very susceptible to antibiotics especially aminosides (100%) polymyxine E (92%), cotrimoxazole (91%) and quinolones (90%); 4) hospital bacteria can be found with a low frequency. However, in our study, Staphylococcus aureus has been isolated in 6% of the cases. This seems to be in relation with the passage of patients in an obstetric clinic.

  14. Imaging Pain.

    PubMed

    Martucci, Katherine T; Mackey, Sean C

    2016-06-01

    The challenges and understanding of acute and chronic pain have been illuminated through the advancement of central neuroimaging. Through neuroimaging research, new technology and findings have allowed us to identify and understand the neural mechanisms contributing to chronic pain. Several regions of the brain are known to be of particular importance for the maintenance and amplification of chronic pain, and this knowledge provides novel targets for future research and treatment. This article reviews neuroimaging for the study of chronic pain, and in particular, the rapidly advancing and popular research tools of structural and functional MRI. PMID:27208709

  15. Managing Neuropathic Pain in Dogs

    PubMed Central

    Moore, Sarah A.

    2016-01-01

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

  16. Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

    PubMed

    Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

    2016-04-01

    Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

  17. Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

    PubMed

    Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

    2016-04-01

    Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD. PMID:26713424

  18. Neck Pain

    MedlinePlus

    ... get better. No 7. Did you have a whiplash-type injury in the past, or do you have pain and/or stiffness every day in your neck, hands, knees, hips or other joints? Yes Your pain may be from DEGENERATIVE CERVICAL ARTHRITIS, a disorder that affects the bones and ...

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

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

  20. Magnetoreception in laboratory mice: sensitivity to extremely low-frequency fields exceeds 33 nT at 30 Hz

    PubMed Central

    Prato, Frank S.; Desjardins-Holmes, Dawn; Keenliside, Lynn D.; DeMoor, Janice M.; Robertson, John A.; Thomas, Alex W.

    2013-01-01

    Magnetoreception in the animal kingdom has focused primarily on behavioural responses to the static geomagnetic field and the slow changes in its magnitude and direction as animals navigate/migrate. There has been relatively little attention given to the possibility that weak extremely low-frequency magnetic fields (wELFMF) may affect animal behaviour. Previously, we showed that changes in nociception under an ambient magnetic field-shielded environment may be a good alternative biological endpoint to orientation measurements for investigations into magnetoreception. Here we show that nociception in mice is altered by a 30 Hz field with a peak amplitude more than 1000 times weaker than the static component of the geomagnetic field. When mice are exposed to an ambient magnetic field-shielded environment 1 h a day for five consecutive days, a strong analgesic (i.e. antinociception) response is induced by day 5. Introduction of a static field with an average magnitude of 44 µT (spatial variability of ±3 µT) marginally affects this response, whereas introduction of a 30 Hz time-varying field as weak as 33 nT has a strong effect, reducing the analgesic effect by 60 per cent. Such sensitivity is surprisingly high. Any purported detection mechanisms being considered will need to explain effects at such wELFMF. PMID:23365198

  1. Pain facilitation and pain inhibition during conditioned pain modulation in fibromyalgia and in healthy controls.

    PubMed

    Potvin, Stéphane; Marchand, Serge

    2016-08-01

    Although fibromyalgia (FM) is associated with a deficit in inhibitory conditioned pain modulation (CPM), the discriminative power of CPM procedures is unknown. Moreover, the high intersubject heterogeneity in CPM responses in FM raises the possibility that a sizeable subgroup of these patients may experience pain facilitation during CPM, but the phenomenon has not been explicitly studied. To address these issues, 96 patients with FM and 71 healthy controls were recruited. Thermal stimuli were used to measure pain thresholds. Pain inhibition was elicited using a tonic thermal test (Peltier thermode) administered before and after activation of CPM mechanisms using a cold pressor test. Thermal pain thresholds were lower in patients with FM than in healthy controls. Pain ratings during the cold pressor test were higher in patients with FM, relative to controls. The CPM inhibitory efficacy was lower in patients with FM than in controls. The CPM procedure had good specificity (78.9%) but low sensitivity (45.7%), whereas a composite pain index had good sensitivity (75.0%) and specificity (78.9%). Finally, the rate of patients with FM who reported pain facilitation during the CPM procedure was found to be significantly increased compared with that of controls (41.7% vs 21.2%). The good discriminative power of the composite pain index highlights the need for further validation studies using mechanistically relevant psychophysical procedures in FM. The low sensitivity of the CPM procedure, combined with the large proportion of patients with FM experiencing pain facilitation during CPM, strongly suggests that endogenous pain inhibition mechanisms are deeply impaired in patients with FM, but only in a subgroup of them. PMID:27045524

  2. Pain facilitation and pain inhibition during conditioned pain modulation in fibromyalgia and in healthy controls.

    PubMed

    Potvin, Stéphane; Marchand, Serge

    2016-08-01

    Although fibromyalgia (FM) is associated with a deficit in inhibitory conditioned pain modulation (CPM), the discriminative power of CPM procedures is unknown. Moreover, the high intersubject heterogeneity in CPM responses in FM raises the possibility that a sizeable subgroup of these patients may experience pain facilitation during CPM, but the phenomenon has not been explicitly studied. To address these issues, 96 patients with FM and 71 healthy controls were recruited. Thermal stimuli were used to measure pain thresholds. Pain inhibition was elicited using a tonic thermal test (Peltier thermode) administered before and after activation of CPM mechanisms using a cold pressor test. Thermal pain thresholds were lower in patients with FM than in healthy controls. Pain ratings during the cold pressor test were higher in patients with FM, relative to controls. The CPM inhibitory efficacy was lower in patients with FM than in controls. The CPM procedure had good specificity (78.9%) but low sensitivity (45.7%), whereas a composite pain index had good sensitivity (75.0%) and specificity (78.9%). Finally, the rate of patients with FM who reported pain facilitation during the CPM procedure was found to be significantly increased compared with that of controls (41.7% vs 21.2%). The good discriminative power of the composite pain index highlights the need for further validation studies using mechanistically relevant psychophysical procedures in FM. The low sensitivity of the CPM procedure, combined with the large proportion of patients with FM experiencing pain facilitation during CPM, strongly suggests that endogenous pain inhibition mechanisms are deeply impaired in patients with FM, but only in a subgroup of them.

  3. Phospholipase D-mediated hypersensitivity at central synapses is associated with abnormal behaviours and pain sensitivity in rats exposed to prenatal stress.

    PubMed

    Sun, Liting; Gooding, Hayley L; Brunton, Paula J; Russell, John A; Mitchell, Rory; Fleetwood-Walker, Sue

    2013-11-01

    Adverse events at critical stages of development can lead to lasting dysfunction in the central nervous system (CNS). To seek potential underlying changes in synaptic function, we used a newly developed protocol to measure alterations in receptor-mediated Ca(2+) fluorescence responses of synaptoneurosomes, freshly isolated from selected regions of the CNS concerned with emotionality and pain processing. We compared adult male controls and offspring of rats exposed to social stress in late pregnancy (prenatal stress, PS), which showed programmed behavioural changes indicating anxiety, anhedonia and pain hypersensitivity. We found corresponding increases, in PS rats compared with normal controls, in responsiveness of synaptoneurosomes from frontal cortex to a glutamate receptor (GluR) agonist, and from spinal cord to activators of nociceptive afferents. Through a combined pharmacological and biochemical strategy, we found evidence for a role of phospholipase D1 (PLD1)-mediated signalling, that may involve 5-HT2A receptor (5-HT2AR) activation, at both levels of the nervous system. These changes might participate in underpinning the enduring alterations in behaviour induced by PS. PMID:23932932

  4. Predicting pain outcomes after traumatic musculoskeletal injury.

    PubMed

    Rosenbloom, Brittany N; Katz, Joel; Chin, Kelly Y W; Haslam, Lynn; Canzian, Sonya; Kreder, Hans J; McCartney, Colin J L

    2016-08-01

    Traumatic musculoskeletal injury results in a high incidence of chronic pain; however, there is little evidence about the nature, quality, and severity of the pain. This study uses a prospective, observational, longitudinal design to (1) examine neuropathic pain symptoms, pain severity, pain interference, and pain management at hospital admission and 4 months after traumatic musculoskeletal injury (n = 205), and (2) to identify predictors of group membership for patients with differing moderate-to-severe putative neuropathic pain trajectories. Data were collected on mechanism of injury, injury severity, pain (intensity, interference, neuropathic quality), anxiety (anxiety sensitivity, general anxiety, pain catastrophizing, pain anxiety), depression, and posttraumatic stress while patients were in-hospital and 4 months after injury. A third of patients had chronic moderate-to-severe neuropathic pain 4 months after injury. Specifically, 11% of patients developed moderate-to-severe pain by 4 months and 21% had symptoms immediately after injury that persisted over time. Significant predictors of the development and maintenance of moderate-to-severe neuropathic pain included high levels of general anxiety while in-hospital immediately after injury (P < 0.001) and symptoms of posttraumatic stress 4 months after injury (P < 0.001). Few patients had adequate pharmacological, physical, or psychological pain management in-hospital and at 4 months. Future research is needed among trauma patients to better understand the development of chronic pain and to determine the best treatment approaches. PMID:27058677

  5. Simultaneous implementation of low dose and high sensitivity capabilities in differential phase contrast and dark-field imaging with laboratory x-ray sources

    NASA Astrophysics Data System (ADS)

    Olivo, A.; Hagen, C. K.; Millard, T. P.; Vittoria, F.; Diemoz, P. C.; Endrizzi, M.

    2014-03-01

    We present a development of the laboratory-based implementation of edge-illumination (EI) x-ray phase contrast imaging (XPCI) that simultaneously enables low-dose and high sensitivity. Lab-based EI-XPCI simplifies the set-up with respect to other methods, as it only requires two optical elements, the large pitch of which relaxes the alignment requirements. Albeit in the past it was erroneously assumed that this would reduce the sensitivity, we demonstrate quantitatively that this is not the case. We discuss a system where the pre-sample mask open fraction is smaller than 50%, and a large fraction of the created beamlets hits the apertures in the detector mask. This ensures that the majority of photons traversing the sample are detected i.e. used for image formation, optimizing dose delivery. We show that the sensitivity depends on the dimension of the part of each beamlet hitting the detector apertures, optimized in the system design. We also show that the aperture pitch does not influence the sensitivity. Compared to previous implementations, we only reduced the beamlet fraction hitting the absorbing septa on the detector mask, not the one falling inside the apertures: the same number of x-rays per second is thus detected, i.e. the dose is reduced, but not at the expense of exposure time. We also present an extension of our phase-retrieval algorithm enabling the extraction of ultra-small-angle scattering by means of only one additional frame, with all three frames acquired within dose limits imposed by e.g. clinical mammography, and easy adaptation to lab-based phase-contrast x-ray microscopy implementations.

  6. Sensitive skin.

    PubMed

    Misery, L; Loser, K; Ständer, S

    2016-02-01

    Sensitive skin is a clinical condition defined by the self-reported facial presence of different sensory perceptions, including tightness, stinging, burning, tingling, pain and pruritus. Sensitive skin may occur in individuals with normal skin, with skin barrier disturbance, or as a part of the symptoms associated with facial dermatoses such as rosacea, atopic dermatitis and psoriasis. Although experimental studies are still pending, the symptoms of sensitive skin suggest the involvement of cutaneous nerve fibres and neuronal, as well as epidermal, thermochannels. Many individuals with sensitive skin report worsening symptoms due to environmental factors. It is thought that this might be attributed to the thermochannel TRPV1, as it typically responds to exogenous, endogenous, physical and chemical stimuli. Barrier disruptions and immune mechanisms may also be involved. This review summarizes current knowledge on the epidemiology, potential mechanisms, clinics and therapy of sensitive skin. PMID:26805416

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

    PubMed Central

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

    2014-01-01

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

  8. Neuropathic pain in children.

    PubMed

    Howard, Richard F; Wiener, Suzanne; Walker, Suellen M

    2014-01-01

    Neuropathic pain (NP), due to a lesion or disease of the somatosensory nervous system, is not well documented or researched in children. NP is a clinical diagnosis that can be difficult, especially in younger children. Nevertheless, it is important to recognise NP, as pain mechanisms and consequently management and prognosis differ from other types of long-term pain. NP is common in adult pain clinics but many of the underlying disease states in which it occurs are infrequently or never encountered in paediatric practice. However, NP in childhood has been reported, even in the very young in certain clinical situations. Causes of NP include traumatic injury, complex regional pain syndrome type II, cancer and chemotherapy, chronic infection, neurological and metabolic disease, and inherited sensory nerve dysfunction. The clinical and laboratory study of traumatic peripheral nerve injury has revealed important age-related differences in clinical presentation and prognosis. It is clear that mechanisms operating during development can profoundly modify the consequences of nerve damage and NP. Clinically, diagnosis, assessment and treatment of NP are based on methods and evidence derived from data in adults. Improvements in the understanding and management of NP are likely to come from developmentally appropriate improvements in the clarity and consistency of diagnosis and systematic, well-researched approaches to treatment.

  9. What a Pain! Kids and Growing Pains

    MedlinePlus

    ... Here's Help White House Lunch Recipes What a Pain! Kids and Growing Pains KidsHealth > For Kids > What a Pain! Kids and ... something doctors call growing pains . What Are Growing Pains? Growing pains aren't a disease. You probably ...

  10. [Acute Chest Pain].

    PubMed

    Gmür, Christian

    2016-02-17

    Acute chest pain is a frequent consultation reason in general practice as well as in emergency departments. With the help of history, physical examination, ECG, laboratory and newly developed risk scores, potentially life-threatening diseases and high-risk patients may be detected and treated early, quickly and cost-effectively. New biomarkers and their combination with risk scores can increase the negative predictive value to exclude certain diseases. PMID:26886697

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Öhrström, E.

    1995-01-01

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

  13. Prevent Back Pain

    MedlinePlus

    ... Back Pain Print This Topic En español Prevent Back Pain Browse Sections The Basics Overview Am I at ... Health: Back Pain . There are different types of back pain. Back pain can be acute or chronic. It ...

  14. Chronic pain - resources

    MedlinePlus

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

  15. GENESIS OF PAIN IN ARTHROSIS

    PubMed Central

    Camanho, Gilberto Luis; Imamura, Marta; Arendt-Nielsen, Lars

    2015-01-01

    Advances in knowledge regarding the pathophysiology of pain among patients with knee osteoarthritis suggest that the central nervous system is involved as a source that maintains and amplifies the painful condition such that it is refractory to conventional orthopedic and rheumatological treatment. Initially, hyperalgesia is observed only at the affected site. However, when the pain becomes refractory, peripheral and central sensitization mechanisms contribute towards maintaining and amplifying the painful conditions, regardless of the peripheral process that originated the pain. At this stage, even removal of the etiological agent may no longer be enough to relieve the painful symptoms. It then becomes necessary to envisage that other factors, distant from the affected joint, may be responsible for the disabling painful condition in such patients. At present, osteoarthrosis does not have any known cure, and the aim of treatment is to lessen the pain while improving function and health-related quality of life, and whenever possible, to minimize the toxicity of the therapy. In the light of emerging evidence suggesting that the central nervous system has a role in the physiopathology of pain in patients with knee arthrosis, the central nervous system should be taken into consideration as a therapeutic target, instead of only administering local treatment using ordinary analgesics, anti-inflammatory drugs and non-pharmacological measures. Thus, methods that modulate the spinal cord and cerebral cortex, including the use of antidepressants, may have a role in managing these patients. PMID:27026978

  16. Ocular neuropathic pain

    PubMed Central

    Rosenthal, Perry; Borsook, David

    2016-01-01

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

  17. Salivary Cytokines as a Minimally-Invasive Measure of Immune Functioning in Young Children: Correlates of Individual Differences and Sensitivity to Laboratory Stress

    PubMed Central

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

    2015-01-01

    There is growing interest in minimally-invasive measures of environmentally-responsive biological systems in developmental science. Contributing to that endeavor, this study explores the intercorrelations, correlates, and task-sensitivity of proinflammatory salivary cytokines in childhood. Saliva was sampled from 125 healthy five-year old children (49% male) across a series of cognitive and emotional challenge laboratory tasks. Samples were assayed for cytokines (IL-1β, IL-6, IL-8, TNFα), and markers of hypothalamic–pituitary– adrenal (HPA) and autonomic nervous system (ANS) activation (salivary cortisol and alpha-amylase [sAA]). Cytokines were positively intercorrelated and task-sensitivity varied. Except IL-8, cytokines were elevated in children with oral health issues and tobacco smoke exposure. Among boys, cytokines were positively related to sAA and negatively related to cortisol. The findings suggest that in healthy children, salivary cytokine levels reflect compartmentalized oral immune activity. Associations between ANS and HPA activity and cytokines in saliva may present opportunities for minimally-invasive methods to explore neuroendocrine-immune interactions during development. PMID:25604242

  18. Orofacial Pain

    MedlinePlus

    ... time. Signs that may indicate a headache of dental origin include: ; Pain behind the eyes Sore jaw muscles or "tired" ... t Sleep? Check Your Bite What Causes a Toothache? Your Posture May Be the Cause of Jaw ...

  19. Abdominal Pain

    MedlinePlus

    ... can help the overall situation for the child. Teaching kids self-hypnosis [8] or guided imagery [8a] ... related topics? Functional Abdominal Pain (English, French or Spanish)—from The North American Society for Pediatric Gastroenterology, ...

  20. Testicle pain

    MedlinePlus

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

  1. Pain Control

    MedlinePlus

    ... have tried to find relief from cancer pain. ■■ Physical Therapy. Exercises or methods used to help restore strength, ... that you see a licensed expert when trying physical therapy, massage, hypnosis, or acupuncture. 25 To learn more ...

  2. Neck pain

    MedlinePlus

    A common cause of neck pain is muscle strain or tension. Most often, everyday activities are to blame. Such activities include: Bending over a desk for hours Having poor posture while watching TV or ...

  3. Face pain

    MedlinePlus

    ... gets worse when you bend forward) Tic douloureux Temporomandibular joint dysfunction syndrome Sometimes the reason for the face pain ... is persistent, unexplained, or accompanied by other unexplained symptoms. Call your primary provider. What to Expect at ...

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

    PubMed Central

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

    2014-01-01

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

  5. Pain relief by touch: a quantitative approach.

    PubMed

    Mancini, Flavia; Nash, Thomas; Iannetti, Gian Domenico; Haggard, Patrick

    2014-03-01

    Pain relief by touch has been studied for decades in pain neuroscience. Human perceptual studies revealed analgesic effects of segmental tactile stimulation, as compared to extrasegmental touch. However, the spatial organisation of touch-pain interactions within a single human dermatome has not been investigated yet. In 2 experiments we tested whether, how, and where within a dermatome touch modulates the perception of laser-evoked pain. We measured pain perception using intensity ratings, qualitative descriptors, and signal detection measures of sensitivity and response bias. Touch concurrent with laser pulses produced a significant analgesia, and reduced the sensitivity in detecting the energy of laser stimulation, implying a functional loss of information within the ascending Aδ pathway. Touch also produced a bias to judge laser stimuli as less painful. This bias decreased linearly when the distance between the laser and tactile stimuli increased. Thus, our study provides evidence for a spatial organisation of intrasegmental touch-pain interactions.

  6. The Effect of Daily Self-Measurement of Pressure Pain Sensitivity Followed by Acupressure on Depression and Quality of Life versus Treatment as Usual in Ischemic Heart Disease: A Randomized Clinical Trial

    PubMed Central

    Bergmann, Natasha; Ballegaard, Søren; Bech, Per; Hjalmarson, Åke; Krogh, Jesper; Gyntelberg, Finn; Faber, Jens

    2014-01-01

    Background Depressive symptoms and reduced quality of life (QOL) are parts of the chronic stress syndrome and predictive of adverse outcome in patients with ischemic heart disease (IHD). Chronic stress is associated with increased sensitivity for pain, which can be measured by algometry as Pressure Pain Sensitivity (PPS) on the sternum. Aim To evaluate if stress focus by self-measurement of PPS, followed by stress reducing actions including acupressure, can decrease depressive symptoms and increase psychological well-being in people with stable IHD. Design Observer blinded randomized clinical trial over 3 months of either intervention or treatment as usual (TAU). Statistical analysis: Intention to treat. Methods Two hundred and thirteen participants with IHD were included: 106 to active treatment and 107 to TAU. Drop-out: 20 and 12, respectively. The active intervention included self-measurement of PPS twice daily followed by acupressure as mandatory action, aiming at a reduction in PPS. Primary endpoint: change in depressive symptoms as measured by Major depression inventory (MDI). Other endpoints: changes in PPS, Well-being (WHO-5) and mental and physical QOL (SF-36). Results At 3 months PPS decreased 28%, to 58, in active and 11%, to 72, in TAU, p<0.001. MDI decreased 22%, to 6.5, in active group vs. 12%, to 8.3 in TAU, p = 0.040. WHO-5 increased to 71.0 and 64.8, active group and TAU, p = 0.015. SF-36 mental score sum increased to 55.3 and 53.3, active and TAU, p = 0.08. Conclusions PPS measurements followed by acupressure reduce PPS, depressive symptoms and increase QOL in patients with stable IHD. Trial Registration ClinicalTrials.gov NCT01513824 PMID:24849077

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

    PubMed

    Vierck, Charles J; Yezierski, Robert P

    2015-04-01

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

  8. Postoperative pain management.

    PubMed

    Joshi, G P

    1994-01-01

    discomfort is now possible for most patients undergoing elective surgical procedures. The aim of an analgesic technique should be not only to lower the pain scores but also to facilitate earlier mobilization and reduce perioperative complications. If future clinical investigations clarify the issues that have been raised by laboratory studies, clinicians may be able to effectively treat postoperative pain using combinations of "balanced," "preemptive," and "peripheral" analgesia. More important, improved analgesic techniques will increase patient satisfaction and enhance their perception of ambulatory anesthesia and surgery. PMID:7960170

  9. Painful Issues in Pain Prediction.

    PubMed

    Hu, Li; Iannetti, Gian Domenico

    2016-04-01

    How perception of pain emerges from neural activity is largely unknown. Identifying a neural 'pain signature' and deriving a way to predict perceived pain from brain activity would have enormous basic and clinical implications. Researchers are increasingly turning to functional brain imaging, often applying machine-learning algorithms to infer that pain perception occurred. Yet, such sophisticated analyses are fraught with interpretive difficulties. Here, we highlight some common and troublesome problems in the literature, and suggest methods to ensure researchers draw accurate conclusions from their results. Since functional brain imaging is increasingly finding practical applications with real-world consequences, it is critical to interpret brain scans accurately, because decisions based on neural data will only be as good as the science behind them. PMID:26898163

  10. Disposition and adjustment to chronic pain.

    PubMed

    Ramírez-Maestre, Carmen; Esteve, Rosa

    2013-03-01

    Several empirical studies have shown that personal characteristics act as differential variables, which determine how pain is experienced and how the chronic pain patient adjusts to pain. The main aim of the present research is to review the relationships between some dispositional characteristics and pain adjustment. Taking into account the empirical literature, 6 personality traits that are relevant to the pain experience have been selected: neuroticism, anxiety sensitivity, and experiential avoidance as risk factors that increase the probability of patients experiencing a disability; and extraversion, optimism, and resilience as personal resources that increase their capacity to manage pain effectively. The results suggest that it would be useful to include an assessment of normal personality structure during the multi-dimensional evaluation of a person with chronic pain. Understanding these individual personality characteristics will aid in designing pain intervention programs and help predict possible treatment outcomes. PMID:23338768

  11. [Myofascial pain syndrome--fascial muscle pain].

    PubMed

    Partanen, Juhani; Ojala, Tuula; Arokoski, Jari P A

    2010-01-01

    Symptoms of myofascial pain syndrome, i.e. fascial muscle pain may occur in several areas of the body, particularly in the neck-shoulder region. The muscle pain symptom in the neck-shoulder region is commonly termed tension neck pain or nonspecific neck pain, but myofascial pain syndrome can also be distinguished into its own diagnosis. This review deals with the clinical picture of myofascial pain syndrome along with pathophysiological hypotheses and treatment options.

  12. Low back pain - acute

    MedlinePlus

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

  13. [Forefoot pain].

    PubMed

    Damiano, Joël

    2010-03-20

    Forefoot chronic pain is a frequent problem in daily clinical practice. Mechanical pathology of the forefoot, usually called static metatarsalgia, represents the most frequent reason for consultation in pathology of the foot. The cause is a functionnal disorder or anatomic derangement of the forefoot architecture. Metatarsalgia can originate from a wide range of affections. Etiologies of chronic pain are described from medial to lateral with first ray pathologies (hallux valgus, hallux rigidus and sesamoid pathology) and first ray insufficiency, pathologies of the second, third and fourth ray and intermetatarsal spaces (second ray syndrome, Freiberg's disease, Morton neuroma, stress or bone insufficiency metatarsal fractures, intermetatarsal bursitis) and fifth ray pathology (lateral bursitis, quintus varus). Sometimes forefoot pain could also be caused by chronic inflammatory rheumatic diseases (rheumatoid and psoriatic arthritis) with a risk of structural metatarsophalangeal joints alteration. The pathology of the toes can, more rarely, explain a forefoot pain. So, several pathologic conditions can produce forefoot pain and the diagnostic approach must always be based on the anamnesis and clinical examination. In a second time if the cause is difficult to establish based solely on clinical findings, radiography and ultrasonography are today the most usefull auxiliary investigations.

  14. Predictors of Abdominal Pain in Depressed Pediatric Inflammatory Bowel Disease Patients

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2010-09-01

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

  16. Chronic Pain Medicines

    MedlinePlus

    ... Treatment of chronic pain usually involves medicines and therapy. Medicines used for chronic pain include pain relievers, antidepressants and anticonvulsants. Different types of medicines help ...

  17. Depressive symptoms and pain evaluations among persons with chronic pain: catastrophizing, but not pain acceptance, shows significant effects.

    PubMed

    Richardson, Elizabeth J; Ness, Timothy J; Doleys, Daniel M; Baños, James H; Cianfrini, Leanne; Richards, J Scott

    2009-12-15

    Cognitive factors such as catastrophic thoughts regarding pain, and conversely, one's acceptance of that pain, may affect emotional functioning among persons with chronic pain conditions. The aims of the present study were to examine the effects of both catastrophizing and acceptance on affective ratings of experimentally induced ischemic pain and also self-reports of depressive symptoms. Sixty-seven individuals with chronic back pain completed self-report measures of catastrophizing, acceptance, and depressive symptoms. In addition, participants underwent an ischemic pain induction procedure and were asked to rate the induced pain. Catastrophizing showed significant effects on sensory and intensity but not affective ratings of the induced pain. Acceptance did not show any significant associations, when catastrophizing was also in the model, with any form of ratings of the induced pain. Catastrophizing, but not acceptance, was also significantly associated with self-reported depressive symptoms when these two variables were both included in a regression model. Overall, results indicate negative thought patterns such as catastrophizing appear to be more closely related to outcomes of perceived pain severity and affect in persons with chronic pain exposed to an experimental laboratory pain stimulus than does more positive patterns as reflected in measures of acceptance.

  18. Genetic basis of pain variability: recent advances.

    PubMed

    Young, Erin E; Lariviere, William R; Belfer, Inna

    2012-01-01

    An estimated 15-50% of the population experiences pain at any given time, at great personal and societal cost. Pain is the most common reason patients seek medical attention, and there is a high degree of individual variability in reporting the incidence and severity of symptoms. Research suggests that pain sensitivity and risk for chronic pain are complex heritable traits of polygenic origin. Animal studies and candidate gene testing in humans have provided some progress in understanding the heritability of pain, but the application of the genome-wide association methodology offers a new tool for further elucidating the genetic contributions to normal pain responding and pain in clinical populations. Although the determination of the genetics of pain is still in its infancy, it is clear that a number of genes play a critical role in determining pain sensitivity or susceptibility to chronic pain. This review presents an update of the most recent findings that associate genetic variation with variability in pain and an overview of the candidate genes with the highest translational potential.

  19. Genetic Basis of Pain Variability: Recent Advances

    PubMed Central

    Young, Erin E.; Lariviere, William R.; Belfer, Inna

    2013-01-01

    An estimated 15–50% of the population experiences pain at any given time, at great personal and societal cost. Pain is the most common reason patients seek medical attention, and there is a high degree of individual variability in reporting the incidence and severity of symptoms. Research suggests that pain sensitivity and risk for chronic pain are complex heritable traits of polygenic origin. Animal studies and candidate gene testing in humans have provided some progress in understanding the heritability of pain, but the application of the genome-wide association methodology offers a new tool for further elucidating the genetic contributions to normal pain responding and pain in clinical populations. Although the determination of the genetics of pain is still in its infancy, it is clear that a number of genes play a critical role in determining pain sensitivity or susceptibility to chronic pain. In the present review, the authors provide an update of the most recent findings that associate genetic variation with variability in pain and an overview of the candidate genes with the highest translational potential. PMID:22058430

  20. A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents.

    PubMed

    McNeill, Daniel R; Wilson, David M

    2007-01-01

    Apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is the primary enzyme in mammals for the repair of abasic sites in DNA, as well as a variety of 3' damages that arise upon oxidation or as products of enzymatic processing. If left unrepaired, APE1 substrates can promote mutagenic and cytotoxic outcomes. We describe herein a dominant-negative form of APE1 that lacks detectable nuclease activity and binds substrate DNA with a 13-fold higher affinity than the wild-type protein. This mutant form of APE1, termed ED, possesses two amino acid substitutions at active site residues Glu(96) (changed to Gln) and Asp(210) (changed to Asn). In vitro biochemical assays reveal that ED impedes wild-type APE1 AP site incision function, presumably by binding AP-DNA and blocking normal lesion processing. Moreover, tetracycline-regulated (tet-on) expression of ED in Chinese hamster ovary cells enhances the cytotoxic effects of the laboratory DNA-damaging agents, methyl methanesulfonate (MMS; 5.4-fold) and hydrogen peroxide (1.5-fold). This MMS-induced, ED-dependent cell killing coincides with a hyperaccumulation of AP sites, implying that excessive DNA damage is the cause of cell death. Because an objective of the study was to identify a protein reagent that could be used in targeted gene therapy protocols, the effects of ED on cellular sensitivity to a number of chemotherapeutic compounds was tested. We show herein that ED expression sensitizes Chinese hamster ovary cells to the killing effects of the alkylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea (also known as carmustine) and the chain terminating nucleoside analogue dideoxycytidine (also known as zalcitabine), but not to the radiomimetic bleomycin, the nucleoside analogue beta-D-arabinofuranosylcytosine (also known as cytarabine), the topoisomerase inhibitors camptothecin and etoposide, or the cross-linking agents mitomycin C and cisplatin. Transient expression of ED in the human cancer cell line NCI-H1299 enhanced cellular

  1. Sensitivity and variability of visual scoring in the comet assay. Results of an inter-laboratory scoring exercise with the use of silver staining.

    PubMed

    García, Omar; Mandina, Tania; Lamadrid, Ana I; Diaz, Adriana; Remigio, Antonia; Gonzalez, Yanela; Piloto, Janet; Gonzalez, Jorge E; Alvarez, Aimeé

    2004-11-22

    Nineteen scorers from seven Cuban laboratories participated in this slide exercise designed to test the influence of the scorer on the accuracy, sensitivity and variability of the comet assay when a visual method of DNA damage evaluation is used. The assay was performed using human lymphocytes from a single donor exposed in vitro for 5 min at 0 degrees C to doses of 0, 5, 10, 25, 50, 100 and 200 microM of hydrogen peroxide. Each participant scored the same set of 14 coded slides with silver stained comets. The comets were classified visually into five categories according to the appearance resulting from the relative proportion of DNA in the tail. The extent of DNA damage was expressed in arbitrary units. At zero dose the median values of 12 scorers out of 19 were included between the values of the overall 25 and 75 per thousand. This proportion remains practically the same as the dose increases. The lowest dose detected by this method for the majority of scorers (11) was 10 microM. The coefficient of variation at the control dose was the highest (median value 26%), progressively declined to 20%, and starting from 25 microM, values are around 10%. The results of the exercise show the reliability of the silver staining and visual scoring for the comet method. PMID:15491629

  2. Neurophysiology of pain and hypnosis for chronic pain.

    PubMed

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

    2012-03-01

    In the past decade there has been a dramatic increase in (1) understanding the neurophysiological components of the pain experiences, (2) randomized clinical trials testing the efficacy of hypnotic treatments on chronic pain, and (3) laboratory research examining the effects of hypnosis on the neurophysiological processes implicated in pain. Work done in these areas has not only demonstrated the efficacy of hypnosis for treating chronic pain but is beginning to shed light on neurophysiological processes that may play a role in its effectiveness. This paper reviews a selection of published studies from these areas of research, focusing on recent findings that have the most potential to inform both clinical work and research in this area. The paper concludes with research and clinical recommendations for maximizing treatment efficacy based on the research findings that are available. PMID:24073099

  3. Complex regional pain syndrome.

    PubMed

    Bruehl, Stephen

    2015-07-29

    Complex regional pain syndrome is a chronic pain condition characterized by autonomic and inflammatory features. It occurs acutely in about 7% of patients who have limb fractures, limb surgery, or other injuries. Many cases resolve within the first year, with a smaller subset progressing to the chronic form. This transition is often paralleled by a change from "warm complex regional pain syndrome," with inflammatory characteristics dominant, to "cold complex regional pain syndrome" in which autonomic features dominate. Multiple peripheral and central mechanisms seem to be involved, the relative contributions of which may differ between individuals and over time. Possible contributors include peripheral and central sensitization, autonomic changes and sympatho-afferent coupling, inflammatory and immune alterations, brain changes, and genetic and psychological factors. The syndrome is diagnosed purely on the basis of clinical signs and symptoms. Effective management of the chronic form of the syndrome is often challenging. Few high quality randomized controlled trials are available to support the efficacy of the most commonly used interventions. Reviews of available randomized trials suggest that physical and occupational therapy (including graded motor imagery and mirror therapy), bisphosphonates, calcitonin, subanesthetic intravenous ketamine, free radical scavengers, oral corticosteroids, and spinal cord stimulation may be effective treatments. Multidisciplinary clinical care, which centers around functionally focused therapies is recommended. Other interventions are used to facilitate engagement in functional therapies and to improve quality of life.

  4. Facts and Figures on Pain

    MedlinePlus

    ... adults. Common chronic pain complaints include headache, low back pain, cancer pain, arthritis pain, neurogenic pain (pain resulting ... Institute of Health Statistics survey indicated that low back pain was the most common (27%), followed by severe ...

  5. When you dislike patients, pain is taken less seriously.

    PubMed

    De Ruddere, Lies; Goubert, Liesbet; Prkachin, Ken Martin; Stevens, Michael André Louis; Van Ryckeghem, Dimitri Marcel Leon; Crombez, Geert

    2011-10-01

    This study examined the influence of patients' likability on pain estimations made by observers. Patients' likability was manipulated by means of an evaluative conditioning procedure: pictures of patients were combined with either positive, neutral, or negative personal traits. Next, videos of the patients were presented to 40 observers who rated the pain. Patients were expressing no, mild-, or high-intensity pain. Results indicated lower pain estimations as well as lower perceptual sensitivity toward pain (i.e., lower ability to discriminate between varying levels of pain expression) with regard to patients who were associated with negative personal traits. The effect on pain estimations was only found with regard to patients expressing high-intensity pain. There was no effect on response bias (i.e., the overall tendency to indicate pain). These findings suggest that we take the pain of patients we do not like less seriously than the pain of patients we like.

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-04-01

    Fibromyalgia is a common disease with a high economic burden. The etiology of this disease remains unclear, as there are no specific abnormalities on clinical or technical examinations. Evidence suggests that central pain sensitization at the brain pain matrix might be involved. Understanding the pain characteristics of this disease is of importance both for diagnosis and treatment. The authors present their findings of pain characteristics in a Belgium population of fibromyalgia patients. Data of 65 patients (57 male and 8 female patients) were analyzed in this study (mean age 46.86, SD = +8.79). Patients filled out the following questionnaires: visual analogue scale, fibromyalgia impact questionnaire, pain-catastrophizing scale, pain vigilance and awareness questionnaire, modified fatigue impact scale, the Beck depression inventory, the short form 36 and the Dutch shortened profile of mood states. Statistical analysis was performed making use of a factor analysis and a hierarchical cluster analysis. We were able to define pain characteristics in this group of patients. The reciprocal effects of mood and fatigue on pain experience could be identified within the data, catastrophizing scores show a high correlation with overall life quality and pain experience. We have performed a cluster analysis on the fibromyalgia patients, based on the four main principal components defining the overall disease burden. Mood explained most of the variance in symptoms, followed by mental health state, fatigue, and catastrophizing. Three clusters of patients could be revealed by these components. Clusters: 1 high scores on mood disorders, pain, and decreased mental health, 2 high scores on fatigue and physical health, and 3 a mixture of these two groups. This data suggest that different subgroups of fibromyalgia patients could be identified and based on that, treatment strategies and results might be adapted. PMID:25048743

  8. [Social pain].

    PubMed

    Shimoyama, Naohito; Shimoyama, Megumi

    2011-09-01

    This chapter focuses on what social pain is and how it should be managed. In order to understand social pain in a cancer patient, it is necessary to recognize the change in the patient's daily life after the diagnosis of cancer. Because the degree of suffering and the relationships with family members and the people he or she worked with differ from patient to patient, it is important to note that the context of social pain is different in each patient. Five points shown below are essential in managing social pain. 1. Economical suffering may be alleviated by utilization of the social security system while taking into account each patient's standard of living. 2. Burdens on family members should be lessened, such as by not having them stay at the patient's bedside every day and letting them go home occasionally. 3. The normal patterns of communication, support, and conflict in the family should be identified, and the extent to which they have been disrupted by the illness should be assessed. 4. It is important to understand the ethnic, cultural, and religious background of the patient and the potential impact of their influence on the individual and the illness. 5. Practical or emotional unfinished business that the patient has needs to be identified, and efforts should be made to support fulfillment.

  9. Breast pain

    PubMed Central

    2007-01-01

    Introduction Breast pain may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20-30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: a low-fat diet, antibiotics, bromocriptine, danazol, diuretics, evening primrose oil, gestrinone, gonadorelin analogues, hormone replacement therapy, lisuride, progestogens, pyridoxine, tamoxifen, tibolone, topical non-steroidal anti-inflammatory drugs, toremifene, and vitamin E. PMID:19454068

  10. Breast pain

    PubMed Central

    2011-01-01

    Introduction Breast pain may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20% to 30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, bromocriptine, combined oral contraceptive pill, danazol, diuretics, evening primrose oil, gestrinone, gonadorelin analogues, hormone replacement therapy (HRT), lisuride, low-fat diet, progestogens, pyridoxine, tamoxifen, tibolone, topical or oral non-steroidal anti-inflammatory drugs (NSAIDs), toremifene, and vitamin E. PMID:21477394

  11. Breast pain

    PubMed Central

    2014-01-01

    Introduction Breast pain may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20% to 30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 11 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: bra wearing, combined oral contraceptive pill, danazol, gonadorelin analogues, progestogens, tamoxifen, and topical or oral non-steroidal anti-inflammatory drugs (NSAIDs).

  12. Achilles Pain.

    ERIC Educational Resources Information Center

    Connors, G. Patrick

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

  13. [Masticatory muscles. Part IX. Pain in the jaw muscles].

    PubMed

    de Laat, A

    1998-03-01

    Masticatory muscle pain is considered as a local expression of myofascial pain. The relationship with Myofascial Pain Syndrome and Fibromyalgia is not well understood. Muscle pain is generated through nociceptors served by small-diameter fibres, where processes of sensitization and neurogenic inflammation are important. In contrast to the 'vicious circle' concept, limitation of movement and loss of muscular power seem to be the result of the pain (pain-adaptation model). The diagnosis of muscle pain is made by algometry, while treatment should be simple, reversible and non-invasive.

  14. Painful menstrual periods

    MedlinePlus

    ... related activities for a few days during each menstrual cycle. Painful menstruation is the leading cause of lost ... when did the pain begin? When in your menstrual cycle do you experience the pain? Is the pain ...

  15. Back Pain During Pregnancy

    MedlinePlus

    ... Management Education & Events Advocacy For Patients About ACOG Back Pain During Pregnancy Home For Patients Search FAQs Back ... Pain During Pregnancy FAQ115, January 2016 PDF Format Back Pain During Pregnancy Pregnancy What causes back pain during ...

  16. When Sex Is Painful

    MedlinePlus

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

  17. Serotonin transporter polymorphism alters citalopram effects on human pain responses to physical pain.

    PubMed

    Ma, Yina; Wang, Chenbo; Luo, Siyang; Li, Bingfeng; Wager, Tor D; Zhang, Wenxia; Rao, Yi; Han, Shihui

    2016-07-15

    Humans exhibit substantial inter-individual differences in pain perception, which contributes to variability in analgesic efficacy. Individual differences in pain sensitivity have been linked with variation in the serotonin transporter gene (5-HTTLPR), and selective serotonin reuptake inhibitors (SSRIs) such as citalopram have been increasingly used as treatments for multiple pain conditions. We combined genotyping, pharmacological challenge, and neuroimaging during painful electrical stimulation to reveal how serotonin genetics and pharmacology interact to influence pain perception and its underlying neurobiological mechanisms. In a double-blind, placebo-controlled procedure, we acutely administrated citalopram (30mgpo) to short/short (s/s) and long/long (l/l) healthy male 5-HTTLPR homozygotes during functional MRI with painful and non-painful electrical stimulation. 5-HTTLPR genotype modulated citalopram effects on pain-related brain responses in the thalamus, cerebellum, anterior insula, midcingulate cortex and inferior frontal cortex. Specifically, citalopram significantly reduced pain-related brain responses in l/l but not in s/s homozygotes. Moreover, the interaction between 5-HTTLPR genotype and pain-related brain activity was a good predictor of the citalopram-induced reductions in pain reports. The genetic modulations of citalopram effects on brain-wide pain processing were paralleled by significant effects on the Neurological Pain Signature, a multivariate brain pattern validated to be sensitive and specific to physical pain. This work provides neurobiological mechanism by which genetic variation shapes brain responses to pain perception and treatment efficacy. These findings have important implications for the types of individuals for whom serotonergic treatments provide effective pain relief, which is critical for advancing personalized pain treatment. PMID:27132044

  18. The negative affect hypothesis of noise sensitivity.

    PubMed

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

    2015-05-01

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

  19. The Negative Affect Hypothesis of Noise Sensitivity

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  1. Pain in fibromyalgia and related conditions.

    PubMed

    Cassisi, G; Sarzi-Puttini, P; Casale, R; Cazzola, M; Boccassini, L; Atzeni, F; Stisi, S

    2014-06-06

    Pain is the hallmark symptom of fibromyalgia (FM) and other related syndromes, but quite different from that of other rheumatic diseases, which depends on the degree of damage or inflammation in peripheral tissues. Sufferers are often defined as patients with chronic pain without an underlying mechanistic cause, and these syndromes and their symptoms are most appropriately described as "central pain", "neuropathic pain", "nonnociceptive pain" or "central sensitivity syndromes". The pain is particular, regional or widespread, and mainly relates to the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is currently considered to be distorted pain or sensory processing, rather than a local or regional abnormality. FM is probably the most important and extensively described central pain syndrome, but the characteristics and features of FM-related pain are similar in other disorders of particular interest for rheumatologists, such as myofascial pain syndromes and temporo-mandibular joint disorders, and there is also an intriguing overlap between FM and benign joint hypermobility syndrome. This suggests that the distinctive aspects of pain in these idiopathic or functional conditions is caused by central nervous system hypersensitivity and abnormalities. Pharmacological and non-pharmacological therapies have been suggested for the treatment of these conditions, but a multidisciplinary approach is required in order to reduce the abnormal cycle of pain amplification and the related maladaptive and self-limiting behaviours.

  2. [Criteria for the evaluation of neonatal pain].

    PubMed

    Ghizzi, C; Benedetti, M; Barlocco, E G

    1996-01-01

    The common opinion about the painful sensation in newborn and in premature baby, is that the experience of pain begins since birth. One of the difficulties in taking care of pain in neonatology is the valuation of the symptom: actually there aren't enough sensitive and standard methods to define and quantify the pain of newborns and prematures babies. The authors illustrate two scales of pain valuation, that have been tested and then adopted by different french groups. These scales allow to examine respectively, the healthy newborn and the newborn after surgical care and permit also an objective measure of newborn malaise sensation. These scores need the valuation of clinical signs and physiological parameters that are sometimes neglected during the execution of invasive techniques; therefore these tables would awaken the sanitary staff to newborn expressions of pain or discomfort, allowing a best comprehension of baby's feelings and facilitating in this nursing and pharmacological interventions to relieve pain.

  3. Recent Advances in Postoperative Pain Management

    PubMed Central

    Vadivelu, Nalini; Mitra, Sukanya; Narayan, Deepak

    2010-01-01

    Good pain control after surgery is important to prevent negative outcomes such as tachycardia, hypertension, myocardial ischemia, decrease in alveolar ventilation, and poor wound healing. Exacerbations of acute pain can lead to neural sensitization and release of mediators both peripherally and centrally. Clinical wind up occurs from the processes of N-Methyl D-Aspartate (NMDA) activation, wind up central sensitization, long-term potentiation of pain (LTP), and transcription-dependent sensitization. Advances in the knowledge of molecular mechanisms have led to the development of multimodal analgesia and new pharmaceutical products to treat postoperative pain. The new pharmacological products to treat postoperative pain include extended-release epidural morphine and analgesic adjuvants such as capsaicin, ketamine, gabapentin, pregabalin dexmetomidine, and tapentadol. Newer postoperative patient-controlled analgesia (PCA) in modes such as intranasal, regional, transdermal, and pulmonary presents another interesting avenue of development. PMID:20351978

  4. The neural bases of social pain: evidence for shared representations with physical pain.

    PubMed

    Eisenberger, Naomi I

    2012-01-01

    Experiences of social rejection or loss have been described as some of the most "painful" experiences that we, as humans, face and perhaps for good reason. Because of our prolonged period of immaturity, the social attachment system may have co-opted the pain system, borrowing the pain signal to prevent the detrimental consequences of social separation. This review summarizes a program of research that has explored the idea that experiences of physical pain and social pain rely on shared neural substrates. First, evidence showing that social pain activates pain-related neural regions is reviewed. Then, studies exploring some of the expected consequences of such a physical pain-social pain overlap are summarized. These studies demonstrate that a) individuals who are more sensitive to one kind of pain are also more sensitive to the other and b) factors that increase or decrease one kind of pain alter the other in a similar manner. Finally, what these shared neural substrates mean for our understanding of socially painful experience is discussed. PMID:22286852

  5. The Biochemical Origin of Pain: The origin of all Pain is Inflammation and the Inflammatory Response. PART 2 of 3 –Inflammatory Profile of Pain Syndromes

    PubMed Central

    2009-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome / reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing

  6. The biochemical origin of pain: the origin of all pain is inflammation and the inflammatory response. Part 2 of 3 - inflammatory profile of pain syndromes.

    PubMed

    Omoigui, Sota

    2007-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby briefly describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome/reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and serve as a foundation to be built upon by other researchers and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain

  7. Feeling the pain of others is associated with self-other confusion and prior pain experience

    PubMed Central

    Derbyshire, Stuart W. G.; Osborn, Jody; Brown, Steven

    2013-01-01

    Some chronic pain patients and healthy individuals experience pain when observing injury or others in pain. To further understand shared pain, we investigated perspective taking, bodily ownership and tooth pain sensitivity. First, participants who reported shared pain (responders) and those who did not (non-responders) viewed an avatar on a screen. Intermittently, 0–3 circles appeared. Sometimes the participant's and avatar's perspective were consistent, both directly viewed the same circles, and sometimes inconsistent, both directly viewed different circles. Responders were faster than non-responders to identify the number of circles when adopting a consistent perspective. Second, participants sat with their left hand hidden while viewing a rubber hand. All participants reported an illusory sensation of feeling stroking in the rubber hand and a sense of ownership of the rubber hand during synchronous stroking of the rubber and hidden hand. The responders also reported feeling the stroking and a sense of ownership of the rubber hand during asynchronous stroking. For experiment three, participants with either low, moderate, or high tooth sensitivity observed a series of images depicting someone eating an ice-popsicle. Low sensitivity participants never reported pain. In contrast, moderate and high sensitivity participants reported pain in response to an image depicting someone eating an ice popsicle (4 and 19% of the time, respectively) and depicting someone eating an ice-popsicle and expressing pain (23 and 40%, respectively). In summary, responders have reduced ability to distinguish their own and others' visual perspective and enhanced ability to integrate a foreign arm into their bodily representation. The tendency to share pain is also enhanced when an observed pain is commonly experienced by the observer. Shared pain may therefore involve reactivation of pain memories or pain schema that are readily integrated into a self perspective and bodily

  8. Understanding pain, part 2: pain management.

    PubMed

    Godfrey, Helen

    This article is the second in a two-part series which explores pain and its management from a physiological perspective. Nurses play an important role in assessing and managing pain. Effective pain management by nurses requires them to have an understanding of the biological basis of the pain interventions which may be used to control pain. This article emphasizes the importance of pain assessment as a precursor for effective pain management and explores the biological basis of pain interventions which contribute to pain control. The role of non-pharmacological approaches in alleviating pain and their actions which contribute to pain relief are explored. The three main types of pharmaceutical agents used, non-opioids, opioids and adjuvant drugs, are introduced and their mechanisms of actions discussed. PMID:16224328

  9. A Comparison of Two Pain Scales in the Assessment of Dental Pain in East Delhi Children

    PubMed Central

    Khatri, Amit; Kalra, Namita

    2012-01-01

    Pain is the most common symptom of oral diseases. Pain perception in children is highly variable and unreliable due to poor communication. Therefore we designed a study to compare pain measurement techniques, that is, visual analogue scale (VAS) and Wong-Baker faces pain rating scale (WBFPS) among Delhi children aged 3 to 14 years undergoing dental extraction. Method. A cross-sectional study was conducted on 180 patients aged 3 to 14 years who had undergone dental extraction. Children were assessed for their pain sensitivity using visual analogue scale (VAS) and Wong-Baker faces pain rating scale (WBFPS ). Result and Conclusion. Pain threshold tends to decline, and the self-management of pain becomes more effective with increasing age. Genderwise result shows that communication ability of boys and girls is similar in all age groups. PMID:22461986

  10. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    PubMed

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  12. Visceral pain and gastrointestinal microbiome.

    PubMed

    Chichlowski, Maciej; Rudolph, Colin

    2015-03-30

    A complex set of interactions between the microbiome, gut and brain modulate responses to visceral pain. These interactions occur at the level of the gastrointestinal mucosa, and via local neural, endocrine or immune activity; as well as by the pro-duction of factors transported through the circulatory system, like bacterial metabolites or hormones. Various psychological, in-fectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain responses. There are critical sensitive periods that can impact visceral pain responses in adulthood. In this review we provide a brief background of the intestinal microbiome and emerging concepts of the bidirectional interactions between the micro-biome, gut and brain. We also discuss recent work in animal models, and human clinical trials using prebiotics and probiotics that alter the microbiome with resultant alterations in visceral pain responses.

  13. Psychophysical and neurochemical abnormalities of pain processing in fibromyalgia.

    PubMed

    Staud, Roland; Spaeth, Michael

    2008-03-01

    Fibromyalgia pain is frequent in the general population, but its pathogenesis is only partially understood. Patients with fibromyalgia lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold). Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain. In the CNS, persistent nociceptive input from peripheral tissues can lead to neuroplastic changes resulting in central sensitization and pain. This mechanism appears to represent a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established, only minimal peripheral input is required for the maintenance of the chronic pain state. Additional factors, including pain-related negative affect and poor sleep have been shown to significantly contribute to clinical fibromyalgia pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.

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

    NASA Astrophysics Data System (ADS)

    Magnuson, S. O.

    2002-05-01

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

  15. Neck pain

    PubMed Central

    2008-01-01

    Introduction Non-specific neck pain has a postural or mechanical basis and affects about two thirds of people at some stage, especially in middle age. Acute neck pain resolves within days or weeks, but may become chronic in about 10% of people. Whiplash injuries follow sudden acceleration–deceleration of the neck, such as in road traffic or sporting accidents. Up to 40% of people continue to report symptoms 15 years after the accident, although this varies between countries. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for people with non-specific neck pain without severe neurological deficit? What are the effects of treatments for acute whiplash injury? What are the effects of treatments for chronic whiplash injury? What are the effects of treatments for neck pain with radiculopathy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 91 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of the evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, biofeedback, drug treatments (analgesics, antidepressants, epidural steroid injections, muscle relaxants, non-steroidal anti-inflammatory drugs [NSAIDs]), early mobilisation, early return to normal activity, exercise, heat or cold, manipulation (alone or plus exercise), mobilisation, multimodal treatment, patient education, percutaneous radiofrequency neurotomy

  16. Shoulder pain

    PubMed Central

    2006-01-01

    Introduction Shoulder pain covers a wide range of problems and affects up to 20% of the population. It is not a specific diagnosis. Shoulder pain can be caused by problems with the acromioclavicular joint, shoulder muscles, or referred pain from the neck. Rotator cuff problems account for 65-70% of cases of shoulder pain. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatment; topical drug treatment; local injections; non-drug treatment; and surgical treatment? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 53 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: arthroscopic laser subacromial decompression, corticosteroid injections (intra-articular), corticosteroids (oral, subacromial injection), electrical stimulation, extracorporeal shock wave therapy, guanethidine (intra-articular), ice, laser treatment, manipulation under anaesthesia (plus intra-articular injection in people with frozen shoulder), multidisciplinary biopsychosocial rehabilitation, nerve block, non-steroidal anti-inflammatory drugs (oral, topical or intra-articular injection), opioid analgesics, paracetamol, phonophoresis, physiotherapy (manual treatment, exercises), surgical arthroscopic decompression, transdermal glyceryl trinitrate, ultrasound.

  17. Shoulder pain

    PubMed Central

    2010-01-01

    Introduction Shoulder pain is a common problem with an estimated prevalence of 4% to 26%. About 1% of adults aged over 45 years consult their GP with a new presentation of shoulder pain every year in the UK. The aetiology of shoulder pain is diverse and includes pathology originating from the neck, glenohumeral joint, acromioclavicular joint, rotator cuff, and other soft tissues around the shoulder girdle. The most common source of shoulder pain is the rotator cuff, accounting for over two-thirds of cases. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatment, topical drug treatment, local injections, non-drug treatment, and surgical treatment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, arthroscopic subacromial decompression, autologous whole blood injection, corticosteroids (oral, subacromial injection, or intra-articular injection), electrical stimulation, excision of distal clavicle, extracorporeal shock wave therapy, ice, laser treatment, manipulation under anaesthesia, suprascapular nerve block, non-steroidal anti-inflammatory drugs (oral, topical or intra-articular injection), opioid analgesics, paracetamol, physiotherapy (manual treatment, exercises), platelet-rich plasma injection

  18. Spontaneous Chronic Pain After Experimental Thoracotomy Revealed by Conditioned Place Preference: Morphine Differentiates Tactile Evoked Pain From Spontaneous Pain.

    PubMed

    Hung, Ching-Hsia; Wang, Jeffrey Chi-Fei; Strichartz, Gary R

    2015-09-01

    Chronic pain after surgery limits social activity, interferes with work, and causes emotional suffering. A major component of such pain is reported as resting or spontaneous pain with no apparent external stimulus. Although experimental animal models can simulate the stimulus-evoked chronic pain that occurs after surgery, there have been no studies of spontaneous chronic pain in such models. Here the conditioned place preference (CPP) paradigm was used to reveal resting pain after experimental thoracotomy. Male Sprague Dawley rats received a thoracotomy with 1-hour rib retraction, resulting in evoked tactile hypersensitivity, previously shown to last for at least 9 weeks. Intraperitoneal injections of morphine (2.5 mg/kg) or gabapentin (40 mg/kg) gave equivalent 2- to 3-hour-long relief of tactile hypersensitivity when tested 12 to 14 days postoperatively. In separate experiments, single trial CPP was conducted 1 week before thoracotomy and then 12 days (gabapentin) or 14 days (morphine) after surgery, followed the next day by 1 conditioning session with morphine or gabapentin, both versus saline. The gabapentin-conditioned but not the morphine-conditioned rats showed a significant preference for the analgesia-paired chamber, despite the equivalent effect of the 2 agents in relieving tactile allodynia. These results show that experimental thoracotomy in rats causes spontaneous pain and that some analgesics, such as morphine, that reduce evoked pain do not also relieve resting pain, suggesting that pathophysiological mechanisms differ between these 2 aspects of long-term postoperative pain. Perspective: Spontaneous pain, a hallmark of chronic postoperative pain, is demonstrated here in a rat model of experimental postthoracotomy pain, further validating the use of this model for the development of analgesics to treat such symptoms. Although stimulus-evoked pain was sensitive to systemic morphine, spontaneous pain was not, suggesting different mechanistic

  19. Spontaneous Chronic Pain After Experimental Thoracotomy Revealed by Conditioned Place Preference: Morphine Differentiates Tactile Evoked Pain From Spontaneous Pain.

    PubMed

    Hung, Ching-Hsia; Wang, Jeffrey Chi-Fei; Strichartz, Gary R

    2015-09-01

    Chronic pain after surgery limits social activity, interferes with work, and causes emotional suffering. A major component of such pain is reported as resting or spontaneous pain with no apparent external stimulus. Although experimental animal models can simulate the stimulus-evoked chronic pain that occurs after surgery, there have been no studies of spontaneous chronic pain in such models. Here the conditioned place preference (CPP) paradigm was used to reveal resting pain after experimental thoracotomy. Male Sprague Dawley rats received a thoracotomy with 1-hour rib retraction, resulting in evoked tactile hypersensitivity, previously shown to last for at least 9 weeks. Intraperitoneal injections of morphine (2.5 mg/kg) or gabapentin (40 mg/kg) gave equivalent 2- to 3-hour-long relief of tactile hypersensitivity when tested 12 to 14 days postoperatively. In separate experiments, single trial CPP was conducted 1 week before thoracotomy and then 12 days (gabapentin) or 14 days (morphine) after surgery, followed the next day by 1 conditioning session with morphine or gabapentin, both versus saline. The gabapentin-conditioned but not the morphine-conditioned rats showed a significant preference for the analgesia-paired chamber, despite the equivalent effect of the 2 agents in relieving tactile allodynia. These results show that experimental thoracotomy in rats causes spontaneous pain and that some analgesics, such as morphine, that reduce evoked pain do not also relieve resting pain, suggesting that pathophysiological mechanisms differ between these 2 aspects of long-term postoperative pain. Perspective: Spontaneous pain, a hallmark of chronic postoperative pain, is demonstrated here in a rat model of experimental postthoracotomy pain, further validating the use of this model for the development of analgesics to treat such symptoms. Although stimulus-evoked pain was sensitive to systemic morphine, spontaneous pain was not, suggesting different mechanistic

  20. Epipericardial fat necrosis as a cause of acute chest pain

    PubMed Central

    Bogale, Vivek; Hurst, David; dePrisco, Gregory

    2016-01-01

    Acute chest pain is one of the most common reasons for presentation to the emergency department. Although most etiologies of chest pain are easy to clinically ascertain with routine history, physical, and laboratory examinations, we present an important benign cause of acute chest pain that may mimic acute coronary syndrome.

  1. Epipericardial fat necrosis as a cause of acute chest pain

    PubMed Central

    Bogale, Vivek; Hurst, David; dePrisco, Gregory

    2016-01-01

    Acute chest pain is one of the most common reasons for presentation to the emergency department. Although most etiologies of chest pain are easy to clinically ascertain with routine history, physical, and laboratory examinations, we present an important benign cause of acute chest pain that may mimic acute coronary syndrome. PMID:27695190

  2. How Reliable Is Laboratory Testing?

    MedlinePlus

    ... to day in a laboratory. The other two, sensitivity and specificity, deal with how well the test ... are frequently monitored by the professional laboratory personnel. Sensitivity and specificity data are determined by research studies ...

  3. Sex differences in a Murine Model of Complex Regional Pain Syndrome.

    PubMed

    Tajerian, Maral; Sahbaie, Peyman; Sun, Yuan; Leu, David; Yang, Hsun Yu; Li, Wenwu; Huang, Ting Ting; Kingery, Wade; David Clark, J

    2015-09-01

    Complex Regional Pain Syndrome (CRPS) is a major cause of chronic pain after surgery or trauma to the limbs. Despite evidence showing that the prevalence and severity of many forms of chronic pain, including CRPS, differ between males and females, laboratory studies on sex-related differences in animal models of CRPS are not available, and the impact of sex on the transition from acute to chronic CRPS pain and disability are unexplored. Here we make use of a tibia fracture/cast mouse model that recapitulates the nociceptive, functional, vascular, trophic, inflammatory and immune aspects of CRPS. Our aim is to describe the chronic time course of nociceptive, motor and memory changes associated with fracture/cast in male and female mice, in addition to exploring their underlying spinal mechanisms. Our behavioral data shows that, compared to males, female mice display lower nociceptive thresholds following fracture in the absence of any differences in ongoing or spontaneous pain. Furthermore, female mice show exaggerated signs of motor dysfunction, deficits in fear memory, and latent sensitization that manifests long after the normalization of nociceptive thresholds. Our biochemical data show differences in the spinal cord levels of the glutamate receptor NR2b, suggesting sex differences in mechanisms of central sensitization that could account for differences in duration and severity of CRPS symptoms between the two groups.

  4. Sex Differences in a Murine Model of Complex Regional Pain Syndrome

    PubMed Central

    Tajerian, Maral; Sahbaie, Peyman; Sun, Yuan; Leu, David; Yang, Hsun Yu; Li, Wenwu; Huang, Ting Ting; Kingery, Wade; Clark, J David

    2015-01-01

    Complex Regional Pain Syndrome (CRPS) is a major cause of chronic pain after surgery or trauma to the limbs. Despite evidence showing that the prevalence and severity of many forms of chronic pain, including CRPS, differ between males and females, laboratory studies on sex-related differences in animal models of CRPS are not available, and the impact of sex on the transition from acute to chronic CRPS pain and disability are unexplored. Here we make use of a tibia fracture/cast mouse model that recapitulates the nociceptive, functional, vascular, trophic, inflammatory and immune aspects of CRPS. Our aim is to describe the chronic time course of nociceptive, motor and memory changes associated with fracture/cast in male and female mice, in addition to exploring their underlying spinal mechanisms. Our behavioral data shows that, compared to males, female mice display lower nociceptive thresholds following fracture in the absence of any differences in ongoing or spontaneous pain. Furthermore, female mice show exaggerated signs of motor dysfunction, deficits in fear memory, and latent sensitization that manifests long after the normalization of nociceptive thresholds. Our biochemical data show differences in the spinal cord levels of the glutamate receptor NR2b, suggesting sex differences in mechanisms of central sensitization that could account for differences in duration and severity of CRPS symptoms between the two groups. PMID:26070658

  5. Satisfaction with and Perception of Pain Management among Palliative Patients with Breakthrough Pain: A Qualitative Study.

    PubMed

    Pathmawathi, Subramanian; Beng, Tan Seng; Li, Lee Mei; Rosli, Roshaslina; Sharwend, Supermanian; Kavitha, Rasaiah R; Christopher, Boey Chiong Meng

    2015-08-01

    Breakthrough pain is a significant contributor to much suffering by patients. The experience of intense pain may interfere with, and affect, daily life functioning and has major consequences on patients' well-being if it is not well managed. The area of breakthrough pain has not been fully understood. This study thus aimed to explore the experiences of breakthrough pain among palliative patients. A qualitative study based on a series of open-ended interviews among 21 palliative patients suffering from pain at an urban tertiary hospital in Malaysia was conducted. Five themes were generated: (i) pain viewed as an unbearable experience causing misery in the lives of patients, (ii) deterioration of body function and no hope of recovery, (iii) receiving of inadequate pain management for pain, (iv) insensitivity of healthcare providers toward patients' pain experience, and (v) pain coping experiences of patients. The findings revealed that nonpharmacologic approaches such as psychosocial support should be introduced to the patients. Proper guidance and information should be given to healthcare providers to improve the quality of patient care. Healthcare providers should adopt a sensitive approach in caring for patients' needs. The aim is to meet the needs of the patients who want to be pain free or to attain adequate relief of their pain for breakthrough pain. PMID:26256219

  6. Pain and Hand Function.

    PubMed

    Howland, Nicholas; Lopez, Mariela; Zhang, Andrew Y

    2016-02-01

    Pain is a unique somatosensory perception that can dramatically affect our ability to function. It is also a necessary perception, without which we would do irreparable damage to ourselves. In this article, the authors assess the impact of pain on function of the hand. Pain can be categorized into acute pain, chronic pain, and neuropathic pain. Hand function and objective measurements of hand function are analyzed as well as the impact of different types of pain on each of these areas.

  7. Conditioned Pain Modulation and Situational Pain Catastrophizing as Preoperative Predictors of Pain following Chest Wall Surgery: A Prospective Observational Cohort Study

    PubMed Central

    Grosen, Kasper; Vase, Lene; Pilegaard, Hans K.; Pfeiffer-Jensen, Mogens; Drewes, Asbjørn M.

    2014-01-01

    Background Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency. Methods Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively. Results Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001). Conclusions Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative

  8. Effects of coping statements on experimental pain in chronic pain patients

    PubMed Central

    Roditi, Daniela; Robinson, Michael E; Litwins, Nola

    2009-01-01

    The present study measured the effects of catastrophizing self-statements and positive coping self-statements on cold pressor-induced pain. Participants were 58 adult chronic pain patients with current facial pain. It was hypothesized that catastrophizing would lead to a decrease in pain endurance whereas positive coping would lead to an increase in pain endurance. It was also hypothesized that catastrophizing would lead to an increase in peak pain intensity whereas positive coping would lead to a decrease in peak pain intensity. At pretest, participants submerged their nondominant hand in the cold pressor. Pain sensitivity ranges (PSR) were subsequently determined by calculating the difference between tolerance and threshold times. Ratings of peak pain intensity were measured using a pressure sensitive bladder/transducer. Participants underwent random assignment to either a catastrophizing group or a positive coping self-statement group. ANCOVA results revealed that on average, participants employing catastrophizing statements as a coping strategy experienced significantly lower PSR (M = 35.53, SD = 39.71) compared to participants employing positive coping self-statements (M = 73.70, SD = 86.14) when controlling for pretest PSR. Group assignment had no significant influence on peak pain intensity ratings. Thus, our results reveal that manipulation of coping causes changes in pain endurance. PMID:21197299

  9. Myofascial pain, fibromyalgia or fibrositis?

    PubMed

    Pearce, J M S

    2004-01-01

    The terms myofascial pain, fibromyalgia and fibrositis are critically examined. They constitute diagnostic labels for non-specific musculoskeletal aches and pains. Analysis of the evidence shows that none of these labels is substantiated by hard physical signs or by laboratory evidence of consistent pathological or biochemical abnormality. What is the objective evidence for disorder(s) of muscle, fascia or fibrous tissues, so clearly indicated by these diagnostic names? Alternative terms such as 'regional pain syndrome' or 'chronic pain syndrome' merely redefine the clinical problem without providing a mechanism or basis for diagnosis. Despite different diagnostic criteria, these conditions, along with chronic fatigue syndrome, have many demographic and clinical similarities, most notably tender trigger points. Indeed, the terms are often used interchangeably. There are few differences in the symptoms, physical findings, laboratory tests, functional status, psychosocial features and psychiatric disorders. This paper seeks not to deny the existence of aches and pains, but to critically examine the utility of these terms. The only claimed physical sign is the presence of tender trigger points over muscles or muscle attachments. Research suggests that tender points are a measure of general distress related to pain complaints but separately associated with fatigue and depression. They are present in some normal subjects and are variable in occurrence in time in the same individual. They reflect no demonstrable pathology. It is therefore argued that none of these commonly used diagnoses represent distinct disease entities. A possible but unproven alternative hypothesis is that such symptoms relate to neural pain with both peripheral and central components, and in some instances psychological or wilful embellishment.

  10. Women, but not men, report increasingly more pain during repeated (un)predictable painful electrocutaneous stimulation: Evidence for mediation by fear of pain.

    PubMed

    Meulders, Ann; Vansteenwegen, Debora; Vlaeyen, Johan W S

    2012-05-01

    An abundance of animal research suggests that fear inhibits pain whereas anxiety increases it. Human studies on this topic are more scarce, and the existing evidence seems rather inconsistent. Therefore, we aimed to investigate the divergent effects of both negative emotional states-that is, pain-related fear and anxiety on pain sensitivity and unpleasantness. Possible sex-related differences were also under investigation, as well as the potential mediational role of fear of movement-related pain on the differences in pain intensity and unpleasantness between both sexes. We employed a voluntary joystick movement paradigm using movements as conditioned stimuli (CSs) and a painful electrocutaneous stimulus as the unconditioned stimulus. Healthy participants received predictable shocks in one condition and unpredictable shocks in another condition. The former procedure is known to induce fear of movement-related pain to the CS+ movement (movement consistently followed by pain), whereas the latter procedure induces (contextual) pain-related anxiety. Results showed that fear of movement-related pain indeed resulted in decreased pain intensity/unpleasantness ratings, while pain-related anxiety led to increased pain intensity/unpleasantness reports. Further, the anticipated sex difference was modulated by time. That is, women gradually reported more pain/unpleasantness, whereas men do not show such a sensitization effect. Moreover, this sex-specific sensitization is partially mediated by (conditioned) fear of movement-related pain. Women also report increasingly more fear of pain over conditioning blocks, while men do not. These results might be interesting in the light of the overrepresentation of women in a number of clinical pain conditions as well as anxiety disorders.

  11. Back pain in astronauts (8-IML-1)

    NASA Technical Reports Server (NTRS)

    Wing, P. C.

    1992-01-01

    As a preliminary study for the International Microgravity Laboratory (IML-1) experiment, a pain diagram was used to elicit information about the incidence and severity of back pain experienced by 20 payload specialists (PS) on 22 shuttle flights from 1983 to 1986. There were 18 responses from 17 PSs (one PS provided information about two missions). Thirteen PSs (72 percent) reported experiencing some degree of back pain, ranging from dull (can be ignored) to severe, making concentration difficult. For the majority, the pain was dull in nature, and did not interfere with work or concentration. For some, the pain abated after only a few minutes; for others, the pain persisted for the entire duration of the flight.

  12. B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina

    PubMed Central

    2011-01-01

    Background Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. Methods We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. Results 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively. The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. Conclusion BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS. Trial Registration ClinicalTrials.gov Identifier: NCT01377402. PMID:21958326

  13. Conditioned pain modulation in women with irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence suggests that patients with irritable bowel syndrome (IBS) are more vigilant to pain-associated stimuli. The aims of this study were to compare women with IBS (n = 20) to healthy control (HC, n = 20) women on pain sensitivity, conditioned pain modulation (CPM) efficiency, and salivary corti...

  14. Recurrent abdominal pain during childhood.

    PubMed Central

    Scott, R. B.

    1994-01-01

    Recurrent abdominal pain is a common presenting complaint among children. A thorough history and physical examination and limited laboratory investigation should enable a physician to make a positive diagnosis of "functional" recurrent abdominal pain in 90% to 95% of cases; an organic cause is identified in only 5% to 10%. The care and thoroughness of the history and physical examination establish the physician's credibility; explaining the clinical basis for the diagnosis and educating the child and parents on what is known about the condition reassures the parents. PMID:8199511

  15. Postoperative pain control.

    PubMed

    Lovich-Sapola, Jessica; Smith, Charles E; Brandt, Christopher P

    2015-04-01

    Prevention and control of postoperative pain are essential. Inadequate treatment of postoperative pain continues to be a major problem after many surgeries and leads to worse outcomes, including chronic postsurgical pain. Optimal management of postoperative pain requires an understanding of the pathoph