Pain Sensitivity Testing Research Articles

Pain sensitivity and injury associated with three methods of disbudding goat kids: Cautery, cryosurgical and caustic paste

Pain sensitivity and skull/brain injury associated with cautery, cryosurgical and caustic paste disbudding were evaluated in goat kids. Kids (reared for meat; n=280) were randomly assigned to one of four treatments (n=70 per treatment): (1) sham-handling (SHAM) or (2) cautery (CAUT), (3) cryosurgical (CRYO) or (4) caustic paste (CASP) disbudding. A pain sensitivity test was carried out 15min pre-treatment and 1h post-treatment. Skull/brain injury was assessed at post-mortem examination. Kids with evidence of injury to the skull/brain, as well as a random sample of kids (n=15 per treatment) without evidence of skull/brain injury, were selected for histological examination of brain tissue. Average daily gains (ADG) were calculated from body weight measurements taken 10min pre-treatment and then at 2, 7 and 14days post-treatment as a measure of the potential effects of pain or injury on growth. CASP and CRYO kids displayed higher pain sensitivity post-treatment than CAUT or SHAM kids, suggesting that they experienced more acute pain 1h post-treatment. One of 70 CAUT kids had a perforated skull, but there was no histological evidence of brain injury in this animal; a further nine CAUT kids exhibited hyperaemia of the skull. The other treatments did not result in injury to the skull/brain. There was no evidence of a difference in ADG across treatments. Caustic paste and cryosurgical disbudding resulted in greater acute pain sensitivity than cautery disbudding; however, cautery disbudding has the potential to cause skull injury if performed incorrectly.

Bindarit Attenuates Pain and Cancer-Related Inflammation by Influencing Myeloid Cells in a Model of Bone Cancer.

C-C motif chemokine ligand 2 (CCL2) is a small cytokine that functions in inflammation and cancer development. Bindarit, a CCL2 inhibitor, is a small anti-inflammatory molecule proven safe by phase II trials in type 2 diabetic nephropathy patients. As cancer-related inflammation is a cause of pain, we investigated whether Bindarit suppresses cancer-related inflammation and pain. We established a bone-cancer mouse model by inoculating cancer cells. After applying Bindarit, we preformed pain sensitivity tests and checked cancer development by X-ray. Using flow cytometry and qRT-PCR assays, we assessed the effect of Bindarit on peripheral blood monocyte mobilization and M2 macrophage polarization. We also investigated the targets of Bindarit using western blotting and luciferase assay. Bindarit-treated mice performed better in pain sensitivity tests compare to control mice. X-ray imaging showed that Bindarit-treated mice had fewer cancer cell colonies and smaller overall tumor burden. Bindarit reduced the number of monocytes in peripheral blood and down-regulated the expression of M2 macrophage polarization makers. Bindarit also inhibited IKKβ phosphorylation. Bindarit efficiently relieves cancer-related pain and suppresses cancer development. Bindarit inhibits monocyte mobilization in peripheral blood as well as M2 macrophage polarization. IKKβ is identified as a target of Bindarit.

PainData: A clinical pain registry in Denmark

Abstract Aims Chronic pain is a significant clinical problem with few effective therapies. Objectives of this clinical registry are (1) to assist clinical decision-making, and (2) facilitate quality assurance and research projects to improve understanding and optimize treatment of patients with chronic pain. Methods PainData is an electronic software system developed for online data capture and clinical reporting, currently implemented in public pain clinics in Odense, Silkeborg, Aalborg, Næstved, Køge and Holbæk. The system captures patient-specific information across several bio-psychosocial domains of pain before the first consultation at the pain clinic as well as immediately after treatment, and 12 months after treatment. The registry also includes information from clinicians (e.g. pain diagnosis, and standardized pain sensitivity testing). PainData is registered as a clinical and research database with the Danish Data Protection Agency (16/39398, 14/44319). Results Since February 1st 2015 more than 3000 patients have completed questionnaires in PainData. The current completion rate at baseline is >80% and at follow-up is close to 50%. Pain-related data (e.g. pain-distribution, psychological distress and use of analgesics) from the registry will be presented on the poster. Conclusions The clinical pain registry contains data from a large cohort of consecutively referred chronic pain patients attending public pain clinics for multidisciplinary assessment and treatment. It contains detailed baseline and outcome data on a broad range of bio-psychosocial factors. The database has significant clinical relevance as it will contribute to an increased understanding of chronic pain conditions as well as contribute to substantial knowledge on how various psychological factors influence the experience of pain and disability in patients with chronic pain. In addition, early prediction of treatment efficacy and future stratification of patients with chronic pain has the potential to optimize treatment outcome. This will be of great interest to both the individual patient and to society.

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

ObjectiveTo evaluate how closely neuropathic-like ocular pain (NOP) symptoms align with a metric of central sensitisation (ie, the presence of persistent ocular pain after topical anaesthetic placement) in individuals with...

Pain Sensitivity and its Relation to Spreading on the Body, Intensity, Frequency, and Duration of Pain: A Cross-Sectional Population-based Study (SwePain).

Individuals with chronic pain often report increased pain sensitivity compared with pain-free individuals; hence, it is crucial to determine whether and how different pain characteristics influence or interact with pain sensitivity. An alternative to experimental pain sensitivity testing is the self-reported pain sensitivity questionnaire (PSQ), which captures pain sensitivity in various body areas.This study compares PSQ in individuals with and without pain and clarifies how pain sensitivity relates to spreading of pain on the body, and to intensity, frequency, duration of pain and to age and sex. A total of 5905 individuals with pain and 572 individuals without pain from the general population in southeastern Sweden completed and returned a postal questionnaire. The mean PSQ score was 3.9 (95% confidence interval [CI], 3.88-3.98) in individuals with pain and 3.5 (95% CI, 3.38-3.64) in pain-free individuals. Hence, PSQ was the highest among individuals with pain, with a difference of 0.4 (95% CI, 0.30-0.56). There was a considerable variation in the PSQ values (mean=3.5; SD=1.54) among pain-free individuals. Pain sensitivity was positively related to spreading, intensity, and frequency of pain, with a correlation coefficient of 0.3. PSQ was higher in widespread pain, 4.5 (95% CI, 4.27-4.69) in women and 4.3 (95% CI, 3.94-4.71) in men, than in local pain, 3.7 (95% CI, 3.61-3.91) in women and 3.8 (95% CI, 3.66-3.95) in men. The score for women with regional pain was between local and widespread pain at 4.0 (95% CI, 3.95-4.11) and that for men with regional pain was 3.8 (95% CI, 3.69-3.87), which is equal to that of local pain. The positive association between pain sensitivity and spreading of pain on the body provides some evidence that the extent of spreading may be related to the degree of pain sensitivity. Before clinical use of PSQ, psychometric development and further research are needed.

Hypoalgesia Induced by Reward Devaluation in Rats

Reduced sensitivity to physical pain (hypoalgesia) has been reported after events involving reward devaluation. Reward devaluation was implemented in a consummatory successive negative contrast (cSNC) task. Food-deprived Wistar rats had access to 32% sucrose during 16 sessions followed by access to 4% sucrose during 3 additional sessions. An unshifted control group had access to 4% sucrose throughout the 19 sessions. Pain sensitivity was measured using von Frey filaments (Experiment 1) and Hargreaves thermal stimuli (Experiment 2) in pretraining baseline, 5 min, and 300 min after either the first (session 17) or second (session 18) devaluation session in the cSNC situation. Sucrose consumption was lower in downshifted groups relative to unshifted groups during postshift sessions—the cSNC effect. Hypoalgesia was observed in downshifted groups relative to unshifted controls when pain sensitivity was assessed 5 min after either the first or second devaluation session, regardless of the pain sensitivity test used. Both pain sensitivity tests yielded evidence of hypoalgesia 300 min after the second downshift session, but not 300 min after the first devaluation session. Whereas hypoalgesia was previously shown only after the second devaluation session, here we report evidence of hypoalgesia after both the first and second devaluation sessions using mechanical and thermal nociceptive stimuli. Moreover, the hypoalgesia observed 300 min after the second devaluation session in both experiments provides unique evidence of the effects of reward loss on sensitivity to physical pain 5 hours after the loss episode. The underlying neurobehavioral mechanisms remain to be identified.

The Relationship among Physical Activity Level, Activity Type, and Thermal Pain Sensitivity

Previous research has shown a relationship between pain sensitivity and daily physical activity. However, it is unclear whether the type of physical activity may also influence pain sensitivity. PURPOSE: The purpose of this study was to examine differences in thermal pain sensitivity among college-aged females who engage in different amounts and types of physically activity. METHODS: Participants (n=27) were tested on two occasions. For the first visit participants went through informed consent, completed a menstrual history questionnaire, and were then familiarized with the protocol for pain sensitivity testing. Participants then wore an accelerometer at the waist for 7 days during waking hours (excluding water activity). The second visit was timed to occur during luteal phase of their menstrual cycle. Pain sensitivity was determined by having participants provide ratings of pain intensity (PI; 0–20) and ratings of pain unpleasantness (PU; 0–20) in response to brief (15-sec) applications of temperatures ranging from 43-49° C. Based upon their self-reported and measured activity levels and activity types participants were placed into the following groups: aerobically trained (AERO), resistance trained (RES), aerobic and resistance trained (A+R), and sedentary (SED). RESULTS: Total activity differed among the groups with the AERO (203±83 min) and A+R (183±28 min) groups accumulating more physical activity compared to the RES (39±39 min; p<0.05) and SED (62±32 min; p<0.05) groups. AERO (32±13 min) and A+R (34±7 min) also accumulated greater “vigorous” intensity activity than the RES (10±4 min; p<0.05) and SED (12±5 min) groups. Mean ratings of PI across all temperatures did not differ among activity groups for (6.0±3.2, 7.4±2.9, 6.6±3.5, and 5.3±3.3 for AERO, RES, A+R, and SED, respectively; p=0.652) nor did ratings of PU across all temperatures (4.1±2.3, 4.6±2.5. 4.5±3.0, and 3.5±2.4 for AERO, RES, A+R, and SED, respectively; p=0.78). CONCLUSIONS: Unlike previous results in middle-aged and older women where higher activity was associated with lower pain sensitivity, our results suggest pain sensitivity does not differ among individuals with differing activity levels in college-aged females. Additionally, we demonstrated pain sensitivity also did not differ among differing types of physical activity.

(319) The role of central sensitization in pain hypersensitivity in individuals with symptoms of migraine headache

Repeated migraine attacks are associated with maladaptive neural plasticity and lead to chronic headache. Sensitization of the pain pathways could play an important role in migraine’s pathophysiology and in the transition to the chronic forms of the disorder. In a previous study our laboratory found that subjects with a history of adverse childhood events presented a significantly increased area of capsaicin-induced secondary hyperalgesia, a measure of central sensitization, suggesting that exposure to trauma dysregulates neurogenic inflammation and pain modulatory systems. In addition, results from a recent study suggest that exposure to maltreatment can induce oxytocin dysregulation, which may also contribute to increased pain sensitivity. The goals of this study were to evaluate the differences in laboratory-induced pain and central sensitization between migraineurs and healthy controls. In addition, we explored whether childhood trauma and oxytocin levels mediate pain hypersensitivity. Thirty-three individuals with migraine headache and thirty-two healthy individuals underwent pain sensitivity testing following topical capsaicin application to the volar forearm. Childhood trauma, oxytocin levels and psychological measures were also assessed. We observed a significant increase in the area of secondary hyperalgesia (p=0.019) as well as capsaicin-induced unpleasantness (p=0.018) in migraineurs compared to healthy controls. However, no significant difference in oxytocin levels (p=0.110; Mann-Whitney U-test) and reported childhood traumatic events (p=0.055; Mann-Whitney U-test) were found between groups.

(182) Vulvodynia is not created equally: pain-related distress subgroups in vulvodynia

Women with vulvodynia exhibit elevated psychological distress associated with negative perceptions of pain compared to pain-free women, including catastrophizing, anxiety, and depression. Unclear from existing data is if women with vulvodynia experience similar levels of pain-related distress and pain sensitivity. Empirical classification of women with vulvodynia is needed in order to identify subgroups of women with vulvodynia who may better respond to specific treatments. Thus, the objective of this study is to identify unique subgroups of women with vulvodynia based on pain sensitivity measures and psychological distress. Baseline self-reported data from 131 patients with vulvodynia enrolled in the National Vulvodynia Registry were included in this analysis. Patients completed the Coping Strategies Questionnaire catastrophizing subscale, State Trait Anxiety Index, McGill Pain Questionnaire Affective Pain subscale, and the Beck Depression Index. Patients underwent standardized pain sensitivity testing of the vulvar vestibule and puborectalis muscles. Prior to conducting cluster analysis, raw scores for measures were transformed to z scores for standardization. We conducted an exploratory hierarchical agglomerative cluster analysis using Ward’s cluster method and squared Euclidean distances to identify unique subgroups based on distress and pain sensitivity measures. Based on the inspection of the agglomeration coefficients, a 2-cluster solution was derived: high distress (n=67) and low distress (n=64). Follow-up analyses of variance indicated significant subgroup differences on all psychological measures. No subgroup differences existed between any of the pain sensitivity measures. These data suggest that within this sample of women vulvodynia exist different phenotypes related to pain-related distress. The mechanisms underlying vulvodynia may differ in women with this condition. These data are consistent with data from other chronic pain conditions, including spinal pain, fibromyalgia, and whiplash. This work supports existing recommendations that vulvodynia providers should screen for and refer for distress management when indicated.

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

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

Effect of Motor Impairment on Analgesic Efficacy of Dopamine D2/3 Receptors in a Rat Model of Neuropathy.

Testing the clinical efficacy of drugs that also have important side effects on locomotion needs to be properly designed in order to avoid erroneous identification of positive effects when the evaluation depends on motor-related tests. One such example is the evaluation of analgesic role of drugs that act on dopaminergic receptors, since the pain perception tests used in animal models are based on motor responses that can also be compromised by the same substances. The apparent analgesic effect obtained by modulation of the dopaminergic system is still a highly disputed topic. There is a lack of acceptance of this effect in both preclinical and clinical settings, despite several studies showing that D2/3 agonists induce antinociception. Some authors raised the hypothesis that this antinociceptive effect is enhanced by dopamine-related changes in voluntary initiation of movement. However, the extent to which D2/3 modulation changes locomotion at analgesic effective doses is still an unresolved question. In the present work, we performed a detailed dose-dependent analysis of the changes that D2/3 systemic modulation have on voluntary locomotor activity and response to four separate tests of both thermal and mechanical pain sensitivity in adult rats. Using systemic administration of the dopamine D2/3 receptor agonist quinpirole, and of the D2/3 antagonist raclopride, we found that modulation of D2/3 receptors impairs locomotion and exploratory activity in a dose-dependent manner across the entire range of tested dosages. None of the drugs were able to consistently diminish either thermal or mechanical pain perception when administered at lower concentrations; on the other hand, the larger concentrations of raclopride (0.5–1.0 mg/kg) strongly abolished pain responses, and also caused severe motor impairment. Our results show that administration of both agonists and antagonists of dopaminergic D2/3 receptors affects sensorimotor behaviors, with the effect over locomotion and exploratory activity being stronger than the observed effect over pain responses.

Overcoming pain thresholds with multilevel models-an example using quantitative sensory testing (QST) data.

The assessment of somatosensory function is a cornerstone of research and clinical practice in neurology. Recent initiatives have developed novel protocols for quantitative sensory testing (QST). Application of these methods led to intriguing findings, such as the presence lower pain-thresholds in healthy children compared to healthy adolescents. In this article, we (re-) introduce the basic concepts of signal detection theory (SDT) as a method to investigate such differences in somatosensory function in detail. SDT describes participants’ responses according to two parameters, sensitivity and response-bias. Sensitivity refers to individuals’ ability to discriminate between painful and non-painful stimulations. Response-bias refers to individuals’ criterion for giving a “painful” response. We describe how multilevel models can be used to estimate these parameters and to overcome central critiques of these methods. To provide an example we apply these methods to data from the mechanical pain sensitivity test of the QST protocol. The results show that adolescents are more sensitive to mechanical pain and contradict the idea that younger children simply use more lenient criteria to report pain. Overall, we hope that the wider use of multilevel modeling to describe somatosensory functioning may advance neurology research and practice.

Sleep and pain sensitivity in adults.

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.

Physical activity, pain responses to heat stimuli, and conditioned pain modulation in postmenopausal women.

Postmenopausal women (PMW) are at high risk for disabling pain and physical inactivity. This study sought to enhance the understanding of relationships between physical activity (PA) and pain among PMW using heat pain sensitivity test and conditioned pain modulation test. We hypothesized that, compared with active women, (i) inactive women would report higher pain intensity and pain unpleasantness ratings; (ii) inactive women in disabling pain would report higher pain intensity and pain unpleasantness at high, but not low, stimulus intensities; and (iii) inactive women would have less modulation. Sixty-eight PMW rated the pain intensity and pain unpleasantness of hot stimuli presented to the thenar eminence of the hand. A subset of 31 women rated the pain intensity of a test stimulus (noxious heat) and a conditioning stimulus (cold water) as part of the conditioned pain modulation task. PA was assessed objectively with accelerometry. Mixed-model analysis of variance (2 × 4 × 2; PA × Temperature × Pain Status) showed that inactive women in disabling pain rated pain unpleasantness higher than active women in disabling pain (F3,192 = 3.526, ∂η = 0.052, P = 0.016). Significantly lower pain unpleasantness ratings were found at the highest stimulus intensity (49°C) only for active women in disabling pain compared with inactive women in disabling pain (t11 = 2.523, P = 0.028). The other hypotheses were not supported. PA is associated with a reduced sensitivity to the unpleasantness of painful high-intensity heat stimuli among women in disabling pain.

Painful intercourse is significantly associated with evoked pain perception and cognitive aspects of pain in women with pelvic pain.

IntroductionEvidence suggests that painful intercourse, pain-related psychosocial factors, and altered pain processing magnify the pain experience, but it is not clear how these factors are related to each other.AimThe aims were to (i) characterize differences between women with pelvic pain and pain-free women using a battery of pain-related psychosocial measures, clinical pain ratings, and evoked local and remote pain sensitivity; and (ii) examine the relationship between intercourse pain, clinical pain, and local and remote evoked pain sensitivity.MethodsWomen with pelvic pain lasting at least 3 months and pain-free women completed questionnaires and underwent pain sensitivity testing. Self-report measures included clinical pain intensity, pain catastrophizing, pain-related fear, pain anxiety, depression, sexual function, and self-efficacy. Pain sensitivity measures included threshold and tolerance and temporal summation of pain. Separate analyses of variance (anova) were used to test group differences in self-report and pain sensitivity measures. Correlations were calculated among dyspareunia, psychosocial factors, and evoked pain.Main Outcome MeasuresSelf-reported pain and pain sensitivity measures.ResultsTwenty-eight pain-free women and 14 women with pelvic pain participated in this study. Women with pelvic pain reported greater pain intensity and greater psychosocial involvement compared with pain-free women. No differences existed between groups for thermal or pressure measures, but women with pelvic pain rated their pain with pain testing significantly higher than pain-free women. Intercourse pain was significantly associated with affective and sensory pain and pressure pain ratings at the puborectalis, vulvar vestibule, adductor longus tendons, and tibialis anterior muscle.ConclusionsDifferences in local pain ratings suggest that women with pelvic pain perceive stimuli in this region as more painful than pain-free women although the magnitude of stimuli does not differ. Alappattu MJ, George SZ, Robinson ME, Fillingim RB, Moawad N, LeBrun EW, and Bishop MD. Painful intercourse is significantly associated with evoked pain perception and cognitive aspects of pain in women with pelvic pain. Sex Med 2015;3:14–23.

Can Fear, Pain, and Muscle Tension Discriminate Vaginismus from Dyspareunia/Provoked Vestibulodynia? Implications for the New DSM-5 Diagnosis of Genito-Pelvic Pain/Penetration Disorder.

Fear has been suggested as the crucial diagnostic variable that may distinguish vaginismus from dyspareunia. Unfortunately, this has not been systematically investigated. The primary purpose of this study, therefore, was to investigate whether fear as evaluated by subjective, behavioral, and psychophysiological measures could differentiate women with vaginismus from those with dyspareunia/provoked vestibulodynia (PVD) and controls. A second aim was to re-examine whether genital pain and pelvic floor muscle tension differed between vaginismus and dyspareunia/PVD sufferers. Fifty women with vaginismus, 50 women with dyspareunia/PVD, and 43 controls participated in an experimental session comprising a structured interview, pain sensitivity testing, a filmed gynecological examination, and several self-report measures. Results demonstrated that fear and vaginal muscle tension were significantly greater in the vaginismus group as compared to the dyspareunia/PVD and no-pain control groups. Moreover, behavioral measures of fear and vaginal muscle tension were found to discriminate the vaginismus group from the dyspareunia/PVD and no-pain control groups. Genital pain did not differ significantly between the vaginismus and dyspareunia/PVD groups; however, genital pain was found to discriminate both clinical groups from controls. Despite significant statistical differences on fear and vaginal muscle tension variables between women suffering from vaginismus and dyspareunia/PVD, a large overlap was observed between these conditions. These findings may explain the great difficulty health professionals experience in attempting to reliably differentiate vaginismus from dyspareunia/PVD. The implications of these data for the new DSM-5 diagnosis of Genito-Pelvic Pain/Penetration Disorder are discussed.

Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer disease compared to healthy control subjects

Patients with Alzheimer disease (AD) report pain less frequently than their cognitively intact peers. It has been hypothesized that pain processing is altered in AD. The aim of this study was to investigate agreement and reliability of 3 pain sensitivity tests and to examine pain threshold and tolerance in patients with AD. We examined 29 patients with mild to moderate AD and 29 age- and gender-matched healthy control subjects with quantitative sensory testing, ie, assessments of detection threshold (warmth detection threshold [WDT]) and pain threshold (heat pain threshold [HPT], pressure algometry, cold pressor test), and assessments of tolerance (pressure algometry, cold pressor test). All procedures were done twice on day 1, 1hour apart, and repeated on day 2. We found no difference between groups for WDT (patient vs control subjects: mean [95% confidence interval]: 35.5°C [33.4°C to 37.6°C] vs 35.4°C [34.3°C to 36.5°C], P=.8) or HPT (41.2°C [40.0°C to 42.4°C] vs 42.3°C [41.1°C to 43.5°C], P=.24). We observed comparable thresholds for pressure algometry (median [25% to 75% interquartile range]: 120kPa [100 to 142kPa] vs 131kPa [113 to 192kPa], P=.10), but significantly lower tolerance in AD patients (213kPa [188 to 306kPa] vs 289kPa [262 to 360kPa], P=.008). No differences were found for the cold pressor test. The study demonstrated good replicability of the sensory testing data with comparable data variability, for both groups, which supports the use of these methods in studies of patients with mild to moderate AD. Contrary to previous studies, we observed a reduced pain tolerance in patients with mild to moderate AD, which suggests that the reduced report of pain cannot be explained by reduced processing of painful stimuli.

Increased pain sensitivity among adults reporting irritable bowel syndrome symptoms in a large population-based study

The aim of this study was to examine whether irritable bowel syndrome (IBS) is associated with increased somatic pain sensitivity in a large population-based sample and to test whether this association was independent of sex, age, comorbid chronic pain, and psychological distress. Pain sensitivity tests included assessment of heat-pain threshold (N=4054) and pressure-pain threshold (N=4689) and of cold-pressor pain intensity and tolerance (N=10,487). Cox regression and analysis of variance (ANOVA) were used to assess the relationship between IBS and pain sensitivity in stepwise multivariate models. The prevalence of IBS symptoms meeting the ROME II criteria was 5.3%. Compared with control subjects, IBS cases had reduced cold-pressor tolerance (hazard ratio=1.4, P<.01), increased cold-pressor pain intensity ratings (z-score=+0.20, P<0.01), and lower heat-pain thresholds (z-score=–0.20, P<0.01), after adjusting for sex and age. These results were only slightly attenuated and remained significant when controlling for comorbid chronic pain and psychological distress. Results for pressure-pain threshold were not significant. Heat- and cold-pressor pain sensitivity was greatest for the IBS reporting severe chronic abdominal pain, indicating that hyperalgesia in IBS is related to degree of clinical pain rather than to the diagnosis per se. Because all pain tests were all carried out on the upper extremities, our findings indicate the presence of widespread hyperalgesia in IBS, which may be a contributing factor to the high rate of comorbid pain seen in this patient group.

Superficial Skin Sensitivity Impairment and Skeletal Stability After Sagittal Split Ramus Osteotomy

Adjustable osteosynthesis miniplates are used to facilitate positioning of the mandible after bilateral sagittal split osteotomy (BSSO) to avoid skeletal relapse and occlusal discrepancies. The short Obwegeser BSSO reduces neurosensory disturbances. Adjustable osteosynthesis plates suited for the Obwegeser BSSO are not commercially available. This study tested adjustable miniplates for the short Obwegeser BSSO in advancement of the mandible and correction of facial asymmetry, assessing (1) sensitivity impairment of the lower lip and (2) skeletal stability.A prototype of L-shaped, 6-hole, 2.0-mm miniplate with 2 sliding holes was used. Five patients with facial asymmetry (group 1) and 10 patients with mandibular hypoplasia (group 2) were operated on. Sensitivity of the lower lip was quantified using the pain and thermal sensitivity test before the surgery (T0), 1 week after the surgery (T1), and 12 months after the surgery (T2). The length of the ascending ramus (group 1) and the corpus (group 2) was determined at T1 and T2 using cone beam computed tomographic scans and lateral skull radiographs, respectively.After the surgery, occlusion was adequate. There was no need for revisional surgery. At T2, no patient showed a pathologically reduced sensitivity of the lower lip. The length of the ascending ramus in group 1 and the length of the corpus in group 2 did not have statistically significant changes between T1 and T2.The current study revealed that the adjustable osteosynthesis plates especially designed for the short Obwegeser BSSO can be safely used for the advancement of the mandible and the correction of facial asymmetry, with a minimum risk for neurosensory disturbance and a high skeletal stability.

Improvement in sensory function via granulocyte-macrophage colony-stimulating factor in rat spinal cord injury models

The aim in this study was to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) leads to sensory improvement in rat spinal cord injury (SCI) models. Thirty male Sprague-Dawley rats were included in this study: 10 in the sham group (laminectomy alone without SCI), 10 in the SCI group (SCI treated with phosphate-buffered saline), and 10 in the GM-CSF treatment group (SCI treated with GM-CSF). A locomotor function test and pain sensitivity test were conducted weekly for 9 weeks after SCI or sham injury. Spinal tissue samples from all rats were immunohistochemically examined for the expression of calcitonin gene-related peptide (CGRP) and abnormal sprouting at Week 9 post-SCI. Granulocyte-macrophage colony-stimulating factor treatment improves functional recovery after SCI. In the tactile withdrawal threshold and frequency of the hindlimb paw, the GM-CSF group always responded with a statistically significant lower threshold than the SCI group 9 weeks after SCI (p < 0.05). The response of the forelimb and hindlimb paws to cold in the GM-CSF group always reflected a statistically significant lower threshold than in the SCI group 9 weeks after injury (p < 0.05). Decreased CGRP expression, observed by density and distribution area, was noted in the GM-CSF group (optical density 113.5 ± 20.4) compared with the SCI group (optical density 143.1 ± 18.7; p < 0.05). Treatment with GM-CSF results in functional recovery, improving tactile and cold sense recovery in a rat SCI model. Granulocyte-macrophage colony-stimulating factor also minimizes abnormal sprouting of sensory nerves after SCI.