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There is a need to better understand biological factors that increase the risk of persistent musculoskeletal pain and heightened pain sensitivity. Knowing the heritability (how genes account for differences in people's traits) can enhance the understanding of genetic versus environmental influences of pain and pain sensitivity. However, there are gaps in current knowledge, including the need for intergenerational studies to broaden our understanding of the genetic basis of pain. Data from Gen1 and Gen2 of the Raine Study were used to investigate the heritability of musculoskeletal pain, and pressure and cold pain sensitivity. Participants included parents (Gen 1, n=1092) and their offspring (Gen 2, n=688) who underwent a battery of testing and questionnaires including pressure and cold pain threshold testing and assessments of physical activity, sleep, musculoskeletal pain, mental health and adiposity. Heritability estimates were derived using the Sequential Oliogenic Linkage Analysis Routines (SOLAR) software. Heritability estimates for musculoskeletal pain and pressure pain sensitivity were significant, accounting for between 0.190 and 0.289 of the variation in the phenotype. In contrast, heritability of cold pain sensitivity was not significant. This is the largest intergenerational study to date to comprehensively investigate the heritability of both musculoskeletal pain and pain sensitivity, using robust statistical analysis. This study provides support for the heritability of musculoskeletal pain and pain sensitivity to pressure, suggesting the need for further convergence of genetic and environmental factors in models for the development and/or maintenance of these pain disorders.

Fibromyalgia syndrome (FMS) is a chronic widespread pain condition of unknown aetiology. The role of temperature in FMS pain has not been reviewed systematically. The goal of this study was to review the influences of temperature on pain in FMS, from meteorological and quantitative sensory testing (QST) studies. The review was registered with Prospero: ID-CRD42020167687, and followed PRISMA guidance. Databases interrogated were: MEDLINE (via OVID), EMBASE, PubMed, Web of Science, ScienceDirect, CINAHL, and ProQuest (Feb'20). Exclusion criteria were: age18, animal studies, non-English, and noncontrolled articles. Thirteen studies pertaining to ambient temperature and FMS pain were identified; 9 of these found no uniform relationship. Thirty-five QST studies were identified, 17 of which assessed cold pain thresholds (CPTs). All studies showed numerically reduced CPTs in patients, ranging from 10.9°C to 26.3°C versus 5.9°C to 13.5°C in controls; this was statistically significant in 14/17. Other thermal thresholds were often abnormal. We conclude that the literature provides consistent evidence for an abnormal sensitization of FMS patients' temperature-sensation systems. Additional work is required to elucidate the factors that determine why a subgroup of patients perceive low ambient temperatures as painful, and to characterize that group. PERSPECTIVE: Patients often report increased pain with changes in ambient temperature; even disabling, extreme temperature sensitivity in winter. Understanding this phenomenon may help clinicians provide reassurance and advice to patients and may guide research into the everyday impact of such hypersensitivity, whilst directing future work into the pathophysiology of FMS.

Painful stimuli can disrupt the homeostasis of human body, which is associated with the changes in facial temperature. There is evidence that social touch as a special form of tactile sensation may modulate the transmission of nociception and pain perception. Here, we investigated the influence of social touch on pain-evoked changes in facial temperature and the association with pain perception. Thirty healthy participants were subjected to cold pain during which they held the hand of a romantic partner, a stranger, or an object. Facial temperature was evaluated using thermal infrared imaging. Subjective pain ratings were decreased in the romantic partner touch. Moreover, social touch by a romantic partner resulted in smaller pain-evoked increases in facial temperature, which were associated with greater pain reduction. Our data provide novel evidence that social touch can modulate pain-evoked changes in facial temperature, which may suggest an inhibitory influence on the processing of nociceptive inputs.

ObjectivesThe relationship of pain sensitivity with pain and disability in low back pain (LBP) is complicated. It has been suggested increased understanding of dynamic quantitative sensory testing (QST) might be useful in increasing understanding of these relationships. This study aimed to create subgroups based on participant responses to dynamic QST, profile these subgroups based on multidimensional variables (including clinical measures of pain and disability, psychological and lifestyle variables and static QST), and investigate the association of subgroup membership with levels of pain intensity, LBP-related disability and disability risk at 12-month follow up.MethodsParticipants (n=273) with dominant axial chronic non-specific LBP with duration of pain >3 months were included in this study. At baseline, eligible participants completed a self-report questionnaire to collect demographic, clinical, psychological and lifestyle data prior to dynamic and static QST. Dynamic QST measures were conditioned pain modulation (CPM) and temporal summation (TS). At 12-months follow up, clinical data were collected, including pain intensity and LBP-related disability. Sub-groups were formed by cross-tabulation. Analysis was undertaken to profile dynamic QST subgroup on demographic, clinical, psychological, lifestyle and static QST measures. Associations between dynamic QST subgroups and follow-up clinical variables were examined.ResultsBased on dynamic QST, participants were allocated into four subgroups; normal CPM and normal TS (n=34, 12.5%); normal CPM and facilitated TS (n=6, 2.2%); impaired CPM and normal TS (n=186, 68.1%); impaired CPM and facilitated TS (n=47, 17.2%). At baseline no differences were demonstrated between subgroups across most clinical variables, or any psychological or lifestyle measures. The two subgroups with impaired CPM were more likely to have a higher number of painful body areas. Cold pain sensitivity was heightened in both the subgroups with facilitated TS. Subgroups did not differ across pain intensity, LBP-related disability and disability risk stratification at follow-up.ConclusionsThe profiles of people with axial LBP did not vary significantly across dynamic QST subgroups, save for those in groups with impaired CPM being more likely to have more widespread symptoms and those with facilitated TS having heightened cold pain sensitivity. Further, subgroup membership was not related to future pain and disability. The role of dynamic QST profiles in LBP remains unclear. Further work is required to understand the role of pain sensitivity in LBP. The utility of dynamic QST subgrouping might not be in determining of future disability. Future research might focus on treatment modifying effects of dynamic QST subgroups.

Objective: Pain assessment is of great importance in both clinical research and patient care. Facial expression analysis is becoming a key part of pain detection because it is convenient, automatic, and real-time. The aim of this study is to present a cold pain intensity estimation experiment, investigate the importance of the spatial-temporal information on facial expression based cold pain, and study the performance of the personalized model as well as the generalized model. Methods: A cold pain experiment was carried out and facial expressions from 29 subjects were extracted. Three different architectures (Inception V3, VGG-LSTM, and Convolutional LSTM) were used to estimate three intensities of cold pain: No pain, Moderate pain, and Severe Pain. Architectures with Sequential information were compared with single-frame architecture, showing the importance of spatial-temporal information on pain estimation. The performances of the personalized model and the generalized model were also compared. Results: A mean F1 score of 79.48% was achieved using Convolutional LSTM based on the personalized model. Conclusion: This study demonstrates the potential for the estimation of cold pain intensity from facial expression analysis and shows that the personalized spatial-temporal framework has better performance in cold pain intensity estimation. Significance: This cold pain intensity estimator could allow convenient, automatic, and real-time use to provide continuous objective pain intensity estimations of subjects and patients.

BackgroundThe experience of pain has been dissociated into two interwoven aspects: a sensory-discriminative aspect and an affective-motivational aspect. We aimed to explore which of the pain descriptors is more deeply rooted in the human brain.FindingsParticipants were asked to evaluate applied cold pain. The majority of the trials showed distinct ratings: some were rated higher for unpleasantness and others for intensity. We compared the relationship between functional data recorded from 7 tesla MRI with unpleasantness and intensity ratings and revealed a stronger relationship between cortical data and unpleasantness ratings.ConclusionsThe present study underlines the importance of the emotional-affective aspects of pain-related cortical processes in the brain. The findings corroborate previous studies showing a higher sensitivity to pain unpleasantness compared to ratings of pain intensity. For the processing of pain in healthy subjects, this effect may reflect the more direct and intuitive evaluation of emotional aspects of the pain system, which is to prevent harm and to preserve the physical integrity of the body.

Background: Substantial literature has demonstrated racial differences in pain perception and endogenous pain modulation is proposed to be a mechanism for the racial differences. Although Indians in Singapore reported higher pain severity than Chinese, the only study on racial difference in experimental pain response in Singapore did not find any difference between the two racial groups. Purpose: The aim of this study was to investigate pain sensitivity and conditioned pain modulation in Chinese and Indians in Singapore. Patients and methods: Sixty age-and sex-matched (30 Chinese 50% female, 30 Indian, 50% female) healthy adults participated in this study. Pressure pain threshold, thermal pain threshold and cold pain tolerance were measured. Conditioned pain modulation, general self-efficacy and depression were also tested, in an attempt to assess endogenous pain inhibition and psychological presentation between the two groups. Results: No difference in pain thresholds was found between the two groups. Indians demonstrated less cold pain tolerance and less efficacious conditioned pain modulation than Chinese. Conditioned pain modulation was a mediator between race and cold pain tolerance. Conclusion: These findings of racial disparities in pain tolerance and endogenous pain inhibition could possibly contribute to the higher pain severity in Indians.

Intercellular adhesion molecule-1 (ICAM-1) mediates extravasation of leukocytes, releasing proinflammatory cytokines or endogenous opioids in the inflamed tissue. Thus, ICAM-1 is a crucial component of peripheral antinociception. Previously, we demonstrated a significant correlation between the soluble form of ICAM (sICAM-1) in serum and pain intensity reported by chronic pain patients. The present study examines the role and kinetics of sICAM-1 in experimentally induced acute pain. Three groups of 10 subjects were exposed to 10 min of high (capsaicin-enhanced) or low-intensity heat pain or cold pain, respectively. Thermal stimuli were induced using a device for quantitative sensory testing. Topical capsaicin significantly increased heat pain intensity without the risk of thermal tissue damage. Pain intensity was recorded every minute during testing. sICAM-1 concentrations in serum were determined by ELISA before, immediately after, and 60 min after test termination. Among all experimental groups, sICAM-1 significantly decreased immediately after pain induction. After 60 min, sICAM-1 concentrations returned towards initial values. Interestingly, a linear correlation was found between the extent of sICAM-1 changes and the initial concentrations. Whereas high initial values led to a distinct decrease of sICAM-1, low concentrations tended to increase. There was no statistically significant correlation between levels or alterations of serum sICAM-1 and pain intensity reported by the test subjects. In contrast to our previous findings in chronic pain patients, the present results show that sICAM-1 values do not correlate with the intensity of acute experimental pain. However, we were able to detect short-term changes of sICAM-1 after induction of nociceptive thermal stimuli, suggesting that this marker is part of a demand-oriented homeostatically controlled system.

Highlights • Normal limits for within-subject comparisons of thermal thresholds are wide. • Our findings advocate for site-specific normal values of adequate resolution. • The difference between distal and proximal thresholds increase drastically with age., Objective Quantitative thermal testing (QTT) is a psychophysical assessment method of small nerve fibers that relies on reference material to assess function. Normal limits for within-subject comparisons of thermal thresholds are scarce, and their association with age, height and sex is not fully elucidated. The aim of this study was to investigate the normal limits for distal-proximal– and contralateral homologous comparisons of thermal thresholds with QTT, and their association with age, sex or height. Methods Fifty healthy volunteers ages 20–79 participated in the experiment. Cold detection thresholds (CDT), warm detection thresholds (WDT), heat pain thresholds (HPT), and cold pain thresholds (CPT) were measured bilaterally at the thenar eminence, anterior thigh, distal medial leg and foot dorsum. Sample normal limits were calculated as (mean) ± 2 SD. Results Forty-eight subjects were included in the analysis. CPT was excluded from all analyses due to a large floor-effect. Sample normal limits for side-differences ranged from 1.8 to 7.2 °C for CDT, 2.4–6.8 °C for WDT and 3.2–4.0 °C for HPT, depending on anatomical site. For distal-proximal comparisons, sample normal limits ranged from 4.0 to 8.7 °C for CDT, 6.0–14.0 °C for WDT and 4.2–9.0 °C for HPT, depending on the pairs compared. Age was associated with side-differences for CDT in the thenar eminences (p

Improving the ability to predict persistent pain after spine surgery would allow identification of patients at risk and guide treatment decisions. Quantitative sensory tests (QST) are measures of altered pain processes, but in our previous study, preoperative QST did not predict pain and disability at single time-points. Trajectory analysis accounts for time-dependent patterns. We hypothesized that QST predict trajectories of pain and disability during 1 year after low back surgery. We performed a trajectory analysis on the cohort of our previous study (n = 141). Baseline QST included electrical, pressure, heat, and cold stimulation of the low back and lower extremity, temporal summation, and conditioned pain modulation. Pain intensity and Oswestry Disability Index were measured before, and 2, 6, and 12 months after surgery. Bivariate trajectories for pain and disability were computed using group-based trajectory models. Multivariable regressions were used to identify QST as predictors of trajectory groups, with sociodemographic, psychological, and clinical characteristics as covariates. Cold pain hypersensitivity at the leg, not being married, and long pain duration independently predicted worse recovery (complete-to-incomplete, incomplete-to-no recovery). Cold pain hypersensitivity increased the odds for worse recovery by 3.8 (95% confidence intervals 1.8-8.0, P < 0.001) and 3.0 (1.3-7.0, P = 0.012) in the univariable and multivariable analyses, respectively. Trajectory analysis, but not analysis at single time-points, identified cold pain hypersensitivity as strong predictor of worse recovery, supporting altered pain processes as predisposing factor for persisting pain and disability, and a broader use of trajectory analysis. Assessment of cold pain sensitivity may be a clinically applicable, prognostic test.

Conditioned pain modulation (CPM) is an endogenous pain inhibition phenomenon that can be summarized simply as one type of pain being able to inhibit another, which must be in a remote area in relation to the first pain. We aimed to compare the effectiveness of four CPM test paradigms as well as the association of the CPM effect with potential predictors in 72 healthy volunteers. Pressure pain from an algometer was used as the test stimulus, and pain provoked by cold water or ischemic pressure was used as the conditioning stimulus, applied either sequentially or in parallel. No significant differences were found between the test paradigms, although the cold-parallel test showed the most significant effect size (&eta, P2 = 0.614). No association was found between the CPM effect and sociodemographic variables (age or sex), nor anxiety, depression, catastrophizing, previous history of pain or self-perceived pain tolerance. Nevertheless, a strong association was found between the CPM effect and individual affinity for the stimulus in participants who underwent the cold water test paradigm, this explained around 45% of the total CPM effect when the paradigm (cold water) coincided with personal affinity for the stimulus (&ldquo, I prefer cold to heat&rdquo, &ldquo, cold is not unpleasant&rdquo, ).

[No abstract available] peer-reviewed

This is the peer reviewed version of the following article: Årnes, A.P., Nielsen, C.S., Stubhaug, A., Fjeld, M.K., Hopstock, L.A., Horsch, A., ... Steingrímsdóttir, O.A. (2020). Physical activity and cold pain tolerance in the general population. European Journal of Pain, 25, 637– 650, which has been published in final form at https://doi.org/10.1002/ejp.1699. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Background - The relationship between habitual physical activity (PA) and experimental pain tolerance has been investigated in small samples of young, healthy and/or single‐sex volunteers. We used a large, population‐based sample to assess this relationship in men and women with and without chronic pain. Methods - We used data from the sixth and seventh Tromsø Study surveys (2007–2008; 2015–2016), with assessed pain tolerance of participants with the cold pressor test (CPT: dominant hand in circulating cold water at 3°C, maximum test time 106 s), and self‐reported total amount of habitual PA in leisure time (n = 19,087), exercise frequency (n = 19,388), exercise intensity (n = 18,393) and exercise duration (n = 18,343). A sub‐sample had PA measured by accelerometers (n = 4,922). We used Cox regression to compare CPT tolerance times between self‐reported PA levels. For accelerometer‐measured PA, we estimated hazard ratios for average daily activity counts, and for average daily minutes of moderate‐to‐vigorous PA done in bouts lasting 10 min or more. Models were tested for PA‐sex, and PA‐chronic pain and PA‐moderate‐to‐severe chronic pain interactions. Results - Leisure‐time PA, exercise intensity and exercise duration were positively associated with CPT tolerance (p < .001; p = .011; p < .001). More PA was associated with higher CPT tolerance. At high levels of leisure‐time PA and exercise intensity, men had a significantly higher CPT tolerance than women. Accelerometer‐measured PA was not associated with CPT tolerance. Conclusions - This study is one of the first to show that higher self‐reported habitual PA was connected to higher experimental pain tolerance in a population‐based sample, especially for men. This was not found for accelerometer‐measured PA. Significance - This study finds that higher level of self‐reported leisure‐time physical activity is associated with increased cold pressor pain tolerance in a large population‐based sample. Though present in both sexes, the association is strongest among men. Despite the robust dose–response relationship between pain tolerance and self‐reported activity level, no such relationship was found for accelerometer‐measured activity, reflecting a possible discrepancy in the aspect of physical activity measured. Though the study design does not permit causal conclusions, the findings suggest that increasing physical activity may increase pain tolerance in the general population.

One previous study indicated the significance of trait self-compassion in psychological well-being and adjustment in people with chronic pain. Higher-frequency heart rate variability (HF-HRV) was found to be closely associated with self-compassion and pain coping. The current study was therefore designed to investigate the relationship between self-compassion and experimental pain as well as the impact of HF-HRV. Sixty healthy participants provided self-reported self-compassion and underwent a cold pain protocol during which HF-HRV was evaluated. Results demonstrated a dual relationship between self-compassion and pain, dependent on the level of HF-HRV during pain exposure. Specifically, self-compassion was associated with lower pain in the condition of higher HF-HRV, while there was an inverse relationship between self-compassion and pain when HF-HRV was lower. Our data indicate the significance of HF-HRV in moderating the association between self-compassion and experimental pain.

Multiple genome-wide association studies have identified non-coding single-nucleotide variants (SNVs) near (e.g., rs10166942[C]) or within (rs17862920[T]) the TRPM8 gene that encodes a cold thermosensor is associated with reduced migraine risk. Furthermore, rs10166942[C]) and rs10166942[T]) are more prevalent in populations that reside in hotter and colder climates, respectively. Here we assessed whether these alleles affect TRPM8 expression in humans and human physiologic responses to cold challenge. Here we show that TRPM8 expression is decreased from the chromosome harboring the rs10166942[C] allele in the human dorsal root ganglia. Moreover, carriers of rs10166942[C] required significantly lower temperatures and longer duration of exposure to reach a cold pain threshold (CPTh), which correlated with decreased TRPM8 expression expected in the carriers. This study provides evidence for a genotype-dependent influence on cold pain sensation suggesting that carriers of the reduced migraine risk allele have reduced sensitivity to cold stimuli and that TRPM8 acts as a cold thermosensor and cold pain transducer in humans. Reduced TRPM8 expression and function underpins the migraine protection in carriers of rs10166942[C]; thus, the evaluation of TRPM8 antagonists as migraine therapeutics is warranted. Furthermore, these results provide mechanistic insights for evolutionary positive selection of rs10166942[T] allele in adaptation along latitudinal cline to colder climates.

How obesity affects pain sensitivity in pain-free individuals remains to be fully characterized. Quantitative sensory testing revealed that obese individuals had responses to heat and cold pain that were indistinguishable from nonobese individuals. Thus, obesity alone does not appear to be associated with amplification of nociceptive processing., Introduction: There is emerging evidence suggesting a relationship between obesity and chronic pain. Objectives: The aim of this study was to determine whether pain-free obese individuals display altered pain responses to acute noxious stimuli, thus raising the possibility of greater pain sensitivity and potential susceptibility for chronic pain development. Methods: Psychophysical and anthropometric data were collected from 38 individuals with an obese body mass index (BMI) classification (BMI ≥ 30) and 41 age/sex-matched individuals of a healthy BMI (BMI < 24.9). Because BMI may be an inaccurate index of obesity, additional anthropometric parameters of central adiposity and percent body fat were examined. Pain responses to suprathreshold noxious heat and cold stimuli were examined. Subjects provided pain intensity and unpleasantness ratings to noxious heat (49°C) applied at varying durations and locations (ventral forearm/lower leg). Cold pain ratings, thresholds, and tolerances were obtained after immersion of the hand in a cold-water bath (0–2°C). Between-group differences in pain responses, as well as relationships between pain responses and obesity parameters, were examined. Importantly, confounds that may influence pain such as anxiety, depression, impulsivity, sleepiness, and quality of life were assessed. Results: No between-group differences in pain sensitivity to noxious heat and cold stimuli were found. No relationships were found between central adiposity or body fat (percentage or distribution) and pain responses to noxious heat or cold stimuli. Conclusions: Obesity has minimal influence on pain sensitivity. Accordingly, it is unlikely that obesity alone increases susceptibility for chronic pain development through amplification of nociceptive processes.

Machine learning identified differences in ultraviolet-B– and capsaicin-induced hypersensitization in the quantitative sensory testing parameter patterns acquired in 82 healthy subjects., The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.

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

We investigate how the attenuation of pain with cognitive interventions affects the strength of cortical connections by pursuing a whole brain approach. While receiving tonic cold pain, 20 healthy participants were asked to utilise three different pain attenuation strategies. During a 7T fMRI recording, participants were asked to rate their pain after each single trial. We related the trial-by-trial variability of the attenuation performance to the trial-by-trial functional connectivity of the cortical data.Across all conditions, we found that a higher performance of pain attenuation was predominantly associated with higher functional connectivity. Of note, we observed an association between low pain and high connectivity for regions that belong to the core areas of pain processing, i.e. the insular and cingulate cortices. For one of the cognitive strategies (safe place), the performance of pain attenuation was explained by diffusion tensor imaging metrics of increased white matter integrity.Impact StatementIn a single trial analysis, the more effective attempts to attenuate pain in three different conditions are associated with general higher functional connectivity across the entire brain.

Using electroencephalography (EEG) power measures within conventional delta, theta, alpha, beta, and gamma bands, the aims of the current study were to highlight cortical correlates of subjective perception of cold pain (CP) and the associations of these measures with behavioral inhibition system (BIS), fight-flight-freeze system (FFFS), and behavioral approach system personality traits. EEG was recorded in 55 healthy right-handed women under (i) a white noise interruption detection condition (Baseline); (ii) enduring CP induced by the cold cup test. CP and Baseline EEG band power scores within conventional frequency bands served for covariance analyses. We found that: (1) higher Pain scorers had higher EEG beta power changes at left frontal, midline central, posterior temporal leads; (2) higher BIS was associated with greater EEG delta activity changes at parietal scalp regions; (3) higher FFFS was associated with higher EEG delta activity changes at temporal and left-parietal regions, and with lower EEG gamma activity changes at right parietal regions. High FFFS, compared to Low FFFS scorers, also showed a lower gamma power across the midline, posterior temporal, and parietal regions. Results suggest a functional role of higher EEG beta activity in the subjective perception of tonic pain. EEG delta activity underpins conflict resolution system responsible for passive avoidance control of pain, while higher EEG delta and lower EEG gamma activity changes, taken together, underpin active avoidance system responsible for pain escape behavior.

Background and purpose Diagnosing small-fiber neuropathy (SFN) is challenging because there is no gold-standard test and few diagnostic tests. This study investigated the clinical symptom profile and its associations with the results of quantitative sensory testing (QST) and the quantitative sudomotor axon reflex test (QSART) as well as the quality of life (QOL) in patients with clinically suspected SFN. Methods This study involved 63 patients with clinically suspected length-dependent SFN. Assessments were performed using QST, QSART, SFN Symptoms Inventory Questionnaire, Neuropathic Pain Symptom Inventory, 'Sirim' frequency and 'Sirim' (cold) pain severity, and 36-item Short-Form Health Survey. Multiple logistic and linear regression analyses were performed to predict risk factors for QST or QSART abnormalities and QOL, respectively. Results 'Sirim' and 'Sirim' pain was the most-common (84%) and the most-severe complaint (mean score of 6.3 on a numerical rating scale ranging from 0 to 10) in patients with clinically suspected SFN. The findings of QST [cold detection threshold (CDT)] and QSART were abnormal in 71% (n=45/57) and 62% (n=39/56) of the patients, respectively. An abnormal CDT was correlated with more-severe stabbing pain (odds ratio=2.23, 95% CI=1.02-4.87, p=0.045). Restless-leg symptoms (β=-7.077) and pressure-evoked pain (β=-5.034) were independent predictors of the physical aspects of QOL. Conclusions 'Sirim' pain, similar to cold pain, should be considered a major neuropathic pain in SFN. Among pain characteristics, stabbing pain of a spontaneous paroxysmal nature may be more pronounced in the setting of dysfunctional Aδ fibers with functional autonomic C fibers.

Introduction We recently reported that a majority of opioid-dependent Malay males on methadone therapy are cold pain sensitive. It is postulated that common OPRM1 polymorphisms may be responsible. This study investigated the association between 118A>G (dbSNP rs1799971) and IVS2+691G>C (dbSNP rs2075572) variants on cold pain responses among opioid-dependent Malay males on methadone maintenance therapy. Methods Cold pain responses including pain threshold, pain tolerance, and pain intensity were measured using the cold pressor test. DNA was extracted from the venous blood before polymerase chain reaction genotyping. Repeated measures analysis of variance was used to compare the cold pain responses and OPRM1 polymorphisms (118A>G and IVS2+691G>C) using models including genotype dominant and recessive models, allelic additive models, and analysis of haplotypes and diplotypes. Results A total of 148 participants were recruited. With the recessive model, those with IVS2+691 homozygous CC genotype had a shorter cold pain tolerance time than those without CC genotype (i.e., GG/GC genotype; 29.81 vs. 43.08 s, respectively, P = 0.048). On the other hand, with diplotype analysis, participants with combined homozygous 118 AA genotype and heterozygous IVS2+691 GC genotype (i.e., AC/AG diplotype) had a longer cold pain tolerance time than those without this diplotype (49.34 vs. 31.48 s, respectively, P = 0.043). Cold pain threshold was not associated with any of the 118A>G and IVS2+691G>C variations despite being analyzed using various models (all P > 0.05). Conclusion The IVS2+691 CC genotype and AC/AG diplotype of 118A>G and IVS2+691G>C seem to have opposing roles in pain tolerance among opioid-dependent Malay males on methadone therapy. Haplotypes of OPRM1 may be associated with altered binding affinity. Electronic supplementary material The online version of this article (doi:10.1007/s40122-015-0041-y) contains supplementary material, which is available to authorized users.

Background and objectives The aim of this study was to clarify mechanisms of psychological fibromyalgia treatment by experimentally examining the effectiveness of its core elements. We assessed the effects of cognitive restructuring and acceptance on experimentally-induced heat and cold pain tolerance and pain intensity in fibromyalgia patients. Methods Cold and heat pain were induced in a sample of 60 fibromyalgia patients using a thermode. We conducted ANCOVAs to examine group differences in posttest scores, co-varying for pretest scores. The between-groups factor was the type of instruction provided (acceptance, cognitive restructuring, and a control condition). In addition, we controlled for pain sensitivity, age, and depression. Results We found that acceptance and cognitive restructuring were superior to the control condition in increasing heat pain tolerance, but did not differ from one another. With respect to cold pain tolerance, cognitive restructuring was associated with increases in cold pain tolerance compared to the control condition, while acceptance did not differ either from the control condition or from cognitive restructuring. Limitations Further experimental research on chronic pain treatment mechanisms is needed, particularly research on individually tailoring treatment strategies according to patients characteristics. Conclusion: Results show that both, cognitive restructuring and acceptance instructions, enhance pain tolerance in fibromyalgia patients.

Cold pain threshold (CPT) measures an individual’s pain threshold in response to a cold stimulus. CPT is most accurately determined with specialised equipment; however this technology is not readily accessible to clinicians. Instead, ice has been employed to measure CPT. An optimal ice protocol has not yet been identified. The aim of this study was to evaluate the reliability and validity of two CPT protocols using ice in a young, healthy population. Twenty-two participants aged 22.6 (SD 1.81) years underwent CPT measurements over 6 anatomical sites across 3 protocols, which were repeated in 2 sessions. One protocol measured pain (PVAS) following ice applied for a standardised period of 30 seconds; a second protocol measured time to onset of pain, and the reference standard measured CPT using laboratory equipment (TSA-II). The PVAS protocol demonstrated the best reliability (mean ICC 0.783, 95% CI 0.706 to 0.841), but the Timed protocol demonstrated superior validity compared to the reference standard (mean ICC −0.504, 95% CI −0.621 to −0.365).

Background. To prevent persistent post-surgery pain, early identification of patients at high risk is a clinical need. Supervised machine-learning techniques were used to test how accurately the patients' performance in a preoperatively performed tonic cold pain test could predict persistent post-surgery pain. Methods. We analysed 763 patients from a cohort of 900 women who were treated for breast cancer, of whom 61 patients had developed signs of persistent pain during three yr of follow-up. Preoperatively, all patients underwent a cold pain test (immersion of the hand into a water bath at 2-4 degrees C). The patients rated the pain intensity using a numerical ratings scale (NRS) from 0 to 10. Supervised machine-learning techniques were used to construct a classifier that could predict patients at risk of persistent pain. Results. Whether or not a patient rated the pain intensity at NRS=10 within less than 45 s during the cold water immersion test provided a negative predictive value of 94.4% to assign a patient to the "persistent pain" group. If NRS=10 was never reached during the cold test, the predictive value for not developing persistent pain was almost 97%. However, a low negative predictive value of 10% implied a high false positive rate. Conclusion. Results provide a robust exclusion of persistent pain in women with an accuracy of 94.4%. Moreover, results provide further support for the hypothesis that the endogenous pain inhibitory system may play an important role in the process of pain becoming persistent.

Chinese herbal medicinals that warm the interior and dispel cold and mainly indicated for the treatment of interior cold syndrome are called “Herbs that Warm the Interior” or “Herbs That Dispel Cold.” Herbs that warm the interior are commonly used for the treatment of syndrome caused by external cold invading and directly attacking the spleen and stomach, or syndrome of spleen and stomach deficiency-cold, such as cold pain in the stomach cavity and abdomen, vomiting and diarrhea, and pale tongue with white coating.

The purpose of this study was to after induced delayed onset muscle soreness, the purpose of this study is to present the effective way on skin temperature changes and cold pain for 14 subjects during to applied with only Cold-jet stream and Cold-jet stream with infra red. 14 healthy men and women who delayed onset muscle soreness eccentric contractions induced by exercise and then the biceps alone was applied to the Cold-jet stream. We measured the time that skin temperature fall from room temperature to 10℃(first period), the time rewarmed from 10℃ to 20℃(second period), the time fall again to 10℃(third period) and the time rewarmed again to 20℃(fourth period). Cold-jet stream with infrared combination therapy was performed with the same method. Results of this study were 1st and 2nd experimental cooling experiments in the to fall to 10℃ Cold-jet stream with infrared combination therapy than in the Cold-jet stream was longer(p

OBJECTIVES: Retrospective symptom reports tend to overestimate actual symptom intensity. This study explored how focusing on sensory-perceptual or on affective-motivational aspects of a somatic experience influenced retrospective symptom reports in high and low habitual symptom reporters (HSR). We hypothesized that a focus on affective-motivational aspects of somatic episodes contributes to retrospective overestimation compared to a focus on sensory-perceptual aspects. DESIGN: Dyspnoea (rebreathing) and pain (cold pain) were induced during two experimental sessions in healthy women: 21 high and 24 low HSR, selected using cut-off scores on a symptom checklist. Within-subject manipulation of sensory and affective processing focus (PF) took place at the encoding phase before symptom induction. METHODS: Dyspnoea and pain ratings were collected immediately after the symptom inductions and after 2 weeks. Breathing behaviour was recorded during dyspnoea trials, while affective state and symptom measures were collected after each trial. RESULTS: Compared to pain, dyspnoea induction was perceived as more unpleasant, arousing, and threatening (ps

After assessment of thermal sensitivity during development of a novel cold pain assay, one subject developed postinflammatory hyperpigmentation. Resultant epidermal darkening gradually faded without clinical intervention., Changes in cold temperature sensitivity are often associated with chronic pain conditions. Progress in understanding the neurobiological mechanism underlying these changes and resulting development of effective therapies has been slowed by the accessibility and affordability of devices used to measure thermal sensitivity in humans. To address this gap, we developed an inexpensive method to measure cold pain thresholds in healthy adult volunteers using dry ice and a thermode. However, early in preliminary testing, a subject presented with epidermal postinflammatory hyperpigmentation that lasted for >200 days. Although this response was unique among the small number of subjects in development of the assay, it raised questions as to the safety of the assay design.

Pain among individuals with knee osteoarthritis (OA) is associated with significant disability in older adults, and recent evidence demonstrates enhanced experimental pain sensitivity. Although previous research showed considerable heterogeneity in the OA clinical pain presentation, less is known regarding the variability in responses to experimental pain. The present study included individuals with knee OA (n = 292) who participated in the Understanding Pain and Limitations in Osteoarthritic Disease study and completed demographic and psychological questionnaires followed by a multimodal quantitative sensory testing (QST) session. Quantitative sensory testing measures were subjected to variable reduction procedures to derive pain sensitivity index scores, which in turn were entered into a cluster analysis. Five clusters were significantly different across all pain sensitivity index variables (P < 0.001) and were characterized by: (1) low pain sensitivity to pressure pain (N = 39); (2) average pain sensitivity across most modalities (N = 88); (3) high temporal summation of punctate pain (N = 38); (4) high cold pain sensitivity (N = 80); and (5) high sensitivity to heat pain and temporal summation of heat pain (N = 41). Clusters differed significantly by race, gender, somatic reactivity, and catastrophizing (P < 0.05). Our findings support the notion that there are distinct subgroups or phenotypes based on experimental pain sensitivity in community-dwelling older adults with knee OA, expanding previous findings of similar cluster characterizations in healthy adults. Future research is needed to further understand the pathophysiological mechanisms underlying pain within these subgroups, which may be of added value in tailoring effective treatments for people with OA.

Background Quantitative Sensory Testing (QST) is more often used because of the increasing recognition of small fiber neuropathy. Methods We studied QST in a systematic way in an age-stratified cohort of 83 neurological-free Hispanic Latinamerican patients. Predefined standardized stimuli were applied using the method of limits. Results WDT range from 2.2 to 3.3°C in hands, and from 4.0°C up to 6.6°C in feet. Cold detection threshold range from 2.2 to 3.6°C in hands, and from 2.6°C to 4.5°C in feet. Heat-induced pain (HP) was induced at lower temperatures than previously reported, with a range from 41.8°C to 44.5°C in hands and from 43.2 to 45.7°C in feet. Similar to HP, cold pain was also induced at much higher temperatures, between 21.4–17.3°C in hands and 21.5–16.5°C in feet. Vibratory stimuli ranged from 0.8 to 1.7 μ/sec in hands and from 1.4 to 3.5 μ/sec in feet. Conclusion Temperature and vibration thresholds were similar to those previously reported in other populations except for pain thresholds that were lower in this population than in the Caucasian population.

Previous studies found a relationship between response to experimentally-induced pain and scores for the gender role expectations of pain (GREP) questionnaire. Findings were similar in individuals from America, Portugal and Israel suggesting that gender role expectations may be universal. The aim of this study was to translate and validate Arabic GREP using Factor Analysis and to investigate if sex differences to cold-pressor pain in healthy Libyan men and women are mediated through stereotypical social constructs of gender role expectations and/or pain-related anxiety. One hundred fourteen university students (58 women) underwent two cycles of cold pressor pain test to measure pain threshold, tolerance, intensity, and unpleasantness. Participants also completed the Arabic GREP questionnaire and the Pain Anxiety Symptom Scale-Short form (PASS-20). It was found that Libyan men had higher pain thresholds and tolerances than women (mean difference, 95% CI: threshold = 4.69 (s), -0.72 to 10.1, p = 0.005; tolerance = 13.46 (s), 0.5-26.4, p = 0.018). There were significant differences between sexes in 6 out of 12 GREP items (p < 0.004 after Bonferonni adjustment). The results of mediational analysis showed that GREP factors were the mediators of the effects of sex on pain threshold (z = -2.452, p = 0.014 for Self Sensitivity); (z = -2.563, p = 0.01, for Self Endurance) and on pain tolerance (z = -2.538, p = 0.01 for Self Endurance). In conclusion, sex differences in response to pain were mediated by gender role expectations of pain but not pain-related anxiety.

Spatial summation (SS) and spatial discrimination (SD) are essential for pain perception. In the cold-pain sensation, these processes have hardly been studied. Our aim was to study the SS and SD of cold pain, as well as the SS of cold-pain threshold (CPT) in hairy and glabrous skin. Two discrete stimuli (9 cm2 each) were applied to the forearm with separation distances of 0–40 cm and in addition, a single stimulus on each forearm. For each configuration, the CPT, suprathreshold cold-pain ratings, and the reported number of activated stimuli (SD) were obtained. In another experiment, SS of CPT was tested in the hairy and glabrous skin of the hand using small (2.25 cm2) and large (9 cm2) probe sizes. The SS of CPT and of cold pain existed over separation distances of up to 30–40 cm, at which point SD became better than chance. When the 2 forearms were stimulated, SS was abolished and cold pain was inhibited. CPT was significantly higher in hairy than glabrous skin, but the amount of SS of CPT was similar in the 2 skin types. Noxious cold-evoked thermal qualities were more common in the glabrous than the hairy skin. In conclusion: (1) SS and SD of cold pain are reciprocal; (2) whereas cold pain can summate over large distances, the SD of cold pain is poor; (3) SS of cold pain does not exist between contralateral body sides, however, inhibition occurs; (4) SS is independent of skin type and sensitivity to cold pain; (5) differences in pain quality between hairy and glabrous skin may reflect innervation differences.

Normal heat pain threshold (HPT) and cold pain threshold (CPT) repeatability should be estimated in order to identify thermal allodynia in longitudinal studies, but such data are scarce in the literature. The aim of our study was to estimate normal HPT and CPT repeatability in the face, forehead, neck and hand. In addition, we reviewed briefly normative studies of thermal pain thresholds relevant for headache research. Thermal pain thresholds were measured on three different days in 31 healthy headache-free subjects. Coefficients of repeatability and normal limits were calculated. HPT and CPT were lowest in the face. Pooled across regions, the lower repeatability limit for the test/retest ratio was 63% for HPT and 55% for CPT. The upper normal CPT limit varied between 24.5 degrees C and 29.7 degrees C. Lower HPT limits ranged between 35.5 degrees C and 40.8 degrees C. Quantitative sensory methods provide useful information about headache and pain pathophysiology, and it is important to estimate the normal test/retest repeatability range in follow-up studies.

Studies using quantitative sensory testing (QST) often present incongruent results due to intra- and intersubject as well as interobserver variability which limit widespread use of the technique. Eliminating or reducing the factors responsible for this variability is of great interest, as it increases reliability and reproducibility of QST. Thermal sensory threshold determination is a crucial part of QST. It was previously suggested that the pressure of the thermode on the skin could influence measurements. To verify this, we developed a new thermode with a built-in pressure sensor. Thresholds obtained with this thermode were compared to those obtained with a commercially available thermotesting device (Medoc TSA-II). Heat detection and heat pain detection thresholds were higher, and cold detection thresholds were lower when measured with our thermode than they were with the Medoc thermode. Cold pain detection thresholds did not differ between the thermodes. Analysis of the heat transfer capacity of the thermodes indicated that the material of the skin contact surface of the thermode may play a role in these shifts in threshold values. Altering the thermode pressure on the skin did not affect the thermal thresholds. Furthermore, the intrasubject variability of the measurements (minimal-to-maximal range of measured threshold values in individual subjects) was also not influenced by the pressure with which the thermode was attached to the skin. Our results suggest that the pressure with which the thermode is attached to the skin does not significantly affect the intra- and intersubject reproducibility of the thermal sensory threshold measurements. Muscle Nerve, 2008

Background and Purpose A within-subject randomized controlled trial was conducted to compare monophasic pulsed current (PC) with a frequency of 50 Hz and a phase duration of 500 microseconds with burst-modulated alternating current (BMAC) (1-kHz alternating current, burst modulated at a frequency of 50 Hz with a 20% duty cycle) to establish whether there were differences in hypoalgesic efficacy as assessed by cold pain threshold measurements. Subjects Twenty-two young adults who were healthy and drawn from a population of students of La Trobe University volunteered to participate in the study. Nineteen subjects (7 male, 12 female) met the inclusion criteria. Method Each participant experienced monophasic PC and BMAC. Time to cold pain threshold was measured before, during, and after the electrical stimulation intervention. Results Both PC and BMAC currents were effective at elevating the cold pain threshold, although there was no statistically significant difference between the 2 currents during stimulation. Discussion and Conclusion Pulsed current and BMAC appear to be equally effective at elevating the cold pain threshold. Analysis indicated that if any real difference exists, it would only be apparent with large (100) subject numbers. Any differences in hypoalgesic efficacy thus are not likely to be clinically important.

Background Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents. New method We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured. Results Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: −11.3 °C to −11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours. Comparison Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients. Conclusion Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain.

Objective To evaluate the analgesic effects of interferential therapy (IFT) when using cold and mechanical pain models. The aim was to determine whether the effects of IFT are dependent on the origin of experimental pain. Design Randomised controlled trail. Setting University research laboratory. Participants Twenty pain-free participants. Intervention Each participant was exposed to the two methods of pain induction on different days. Main outcome measures Cold pain threshold (time to first sensation of pain), intensity and unpleasantness measured on a visual analogue scale (VAS); mechanical pain threshold (tolerance to pressure) and unpleasantness (VAS). Results IFT produced similar effects on the threshold (first sensation of pain) for both cold and mechanical pain. The thresholds were significantly increased and the percentage changes in both were similar, as were their standard deviations. This indicates that the analgesia provided by IFT is similar whether the origin of pain is cold or mechanical, and suggests that IFT can affect pain from a range of origins. The effect of IFT on other measures was not as pronounced. With mechanical pain, neither pain tolerance (maximum tolerable pain) nor unpleasantness was significantly altered. With cold pain, both intensity and unpleasantness showed a small but statistically significant change. Conclusions The cold and mechanical pain models are equally effective experimental tools to investigate electroanalgesia. These findings also suggest that future research should not induce pain beyond threshold when using the cold and mechanical pain models, as little additional information is gathered whilst subject discomfort and the risk of tissue damage is increased.

The Marstock method of limits was used to obtain thresholds for detection of cooling, warming, cold pain and heat pain for 34 young adults, upon eight spatially matched sites on the left and right sides of the face, the right ventral forearm and the scalp. Male and female subjects were tested by both a male and a female experimenter. Neither the experimenter nor the gender of the subject individually influenced the thresholds. The thermal thresholds varied greatly across facial sites: sixfold and tenfold for cool and warmth, respectively, from the most sensitive sites on the vermilion to the least sensitive facial site, the preauricular skin. Warm thresholds were 68% higher than cool thresholds, on average, and 12% higher on the left compared to the right side of the face. The mean cold pain threshold increased from 21.0 degrees C on the hairy upper lip to 17.8 degrees C on the preauricular skin. Sites on the upper lip were also most sensitive to noxious heat with pain thresholds of 42-43 degrees C. The scalp was notably insensitive to innocuous and noxious changes in temperature. For the sensations of nonpainful cool and warmth, the more sensitive a site, the less the estimates of the thresholds differed between subjects. In contrast, for heat pain, the more sensitive a site, the more the estimates differed between subjects. Subjects who were relatively more sensitive to cool tended to be relatively more sensitive to warmth. Subjects' sensitivities to nonpainful cool and warmth were less predictive of their sensitivities to painful cold and heat, respectively. Short-term within-subject variability increased with the magnitude of the thresholds. The lower the threshold, the more similar were repeated measurements of it, within a 5-25 s period.

There is some evidence that repetitive transcranial magnetic stimulation (rTMS) can alleviate the experience of chronic pain. The mechanisms by which rTMS may induce pain relief, however, are unknown. The present study examined whether a session of rTMS would produce sensory threshold changes in healthy individuals. Detection and pain thresholds for cold sensations were compared following low frequency (1 Hz) (Experiment 1) and high frequency (20 Hz) (Experiment 2) repetitive TMS. While cold detection threshold was significantly lowered by both rTMS rates, only high frequency rTMS produced a significant change in cold pain threshold. In contrast, sham rTMS did not alter thresholds for cold stimuli. These findings provide evidence that sensory thresholds can be influenced by repetitive transcranial magnetic stimulation.

The present study describes pain- and stress-coping strategies and life satisfaction in subgroups of fibromyalgia patients. Thirty-two females with fibromyalgia syndrome (FMS) and 21 healthy pain-free women were studied. Those with FMS were classified as thermal (both heat and cold) pain sensitive or slightly cold pain sensitive based on pain thresholds determined using a Thermotest device. Global stress-coping styles, life satisfaction, and specific pain-coping strategies were measured. Patients classified as thermal pain sensitive were affected by physical symptoms to a greater extent than were those classified as slightly cold pain sensitive. The thermal pain sensitive group used more diverting attention coping strategies than the slightly cold pain sensitive group did. Separating fibromyalgia patients into subgroups might increase the potential for improving nursing care of these patients. Through the use of effective coping strategies in dealing with stress and pain, life satisfaction may also be enhanced.

Sensory return in a split skin graft is an important factor in the protection of this graft from injury. Hence, three tests were compared: (1) the standard pain test using a simple pin, (2) the cold pain test, and (3) the hot pain test. Both the hot and cold pain tests were performed using the thermal sensory analyzer device. Thirteen patients were investigated; all had split skin grafts applied directly onto deep fascia after malignant melanoma excision on the lower limb. The period after grafting ranged from 4 to 15 years, and the mean age was 46.5 years. The normal contralateral side of each patient was used as the control for that patient. The results were collected in simple data tables and were analyzed using paired t tables for small samples with the level of significance set at p < 0.05. The standard pain test demonstrated that the split skin grafts applied on deep fascia did not recover sensation, even 15 years after surgery (p < 0.001). The hot and cold pain tests were both in agreement with the standard pain test at p < 0.001 and p < 0.03, respectively. The standard pain test is usually performed, as described in this study, using a pin, which is cheap and readily available in any plastic surgery and burn clinic. However, the cold and hot pain tests as performed here using the thermal sensory analyzer device are accurate but are costly, cumbersome, and not available in all clinics except for highly specialized units. Hence, the author would like to dispel the myth that the standard pain test is inaccurate. This might be so in testing sensation in "normal" skin but not in testing the recovery of sensation in a skin graft.

BACKGROUND: Test-retest reliability is important to establish for any diagnostic tool. The reliability of quantitative sensory testing (QST) in the trigeminal region has recently been described in Caucasians as well as differences in absolute thresholds and responses between Caucasians and Chinese. However, the test-retest reliability has not been determined in a Chinese population.OBJECTIVE: To provide novel information on the test-retest reliability of thermal QST in the trigeminal and spinal system in healthy Chinese.METHODS: Twenty healthy volunteers (10 women and 10 men) participated. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), and heat pain threshold (HPT) were measured at two sites: the surface of the left hand and the left masseter. The testing was performed over three consecutive stimuli trials, three sessions conducted on one day and repeated one week later. Data were analyzed with intra-tester reliability test and four-way analysis of variance (ANOVA) for repeated measures.RESULTS: There was a tendency for the first trial in CDT (p = 0.005), CPT (p = 0.02), and HPT (p < 0.001) to reflect higher sensitivity than the subsequent two trials. Most variables showed acceptable to excellent reliability and non-significant difference across different trials (ICC: 0.912-0.989), sessions (ICC: 0.791-0.977), and days (ICC: 0.415-0.837). Between-site differences were significant for CDT (p = 0.003) and HPT (p = 0.045) with higher sensitivity at the masseter muscle. There were significant gender differences with higher sensitivity in women for CPT (p = 0.001) and HPT (p = 0.001).CONCLUSION: Test site and gender affect thermal thresholds substantially. The test-retest reliability of most thermal threshold measures were acceptable for assessing somatosensory function, however, innocuous thresholds appear to be associated with larger variability than noxious thresholds in a Chinese population.

Studies investigating the effect of rate of temperature change on thermal thresholds have used a variety of different methods and threshold combinations, and many display incomplete reporting of statistical analyses. It has been suggested that C- and Adelta-fibre mediated thresholds differ in their reaction to different rates of temperature change. Ten healthy female volunteers (aged 18-26 years; mean 21 +/- S.D. 2.53) undertook cold sensation (CS), warm sensation (WS), cold pain (CP) and heat pain (HP) threshold determinations on the thenar eminence of the dominant hand. Rates of temperature change of 0.5, 1, 2.5 and 4 degrees C/s were used, with a modified method of limits. Adaptation temperature was 32 degrees C and thermode size 3 cm x 3 cm. Results showed a significant increase in WS, HP and CP thresholds with increased rates of temperature change (all p0.001), but no significant change for CS (p = 0.653). These results suggest that thresholds with a C-fibre component (WS, HP and CP) and those that are Adelta-fibre mediated (CS) behave differently. A traditional explanation of measurement artefact alone is insufficient in rationalizing these results, with additional factors potentially involved. Slow rates of temperature change were shown to reduce mean intra-individual differences in recorded threshold values, and also to abolish ceiling effects with HP threshold determinations. Clinically, therefore, using slow rates of temperature change with method of limits has a range of benefits over and above simply minimizing measurement artefact.

BackgroundThere is a dearth of knowledge about the link between cortisol and pain sensitivity.PurposeWe examined the association of salivary cortisol with indices of cold pain sensitivity in 198 female twins and explored the role of familial confounding.MethodsThree-day saliva samples were collected for cortisol levels and a cold pressor test was used to collect pain ratings and time to threshold and tolerance. Linear regression modeling with generalized estimating equations examined the overall and within-pair associations.ResultsLower diurnal variation of cortisol was associated with higher pain ratings at threshold (p = 0.02) and tolerance (p

The thermal grill illusion (TGI) in which interlacing cold and warm bars create the illusion of a painful sensation has been suggested as an experimental model for central pain states and pain processing. The aim of this study was to use this technique to gain further insights into the altered pain perception in major depressive disorder (MDD).In 18 unmedicated patients with MDD, cold and heat pain thresholds (CPT/HPT) as well as the perception of the TGI were examined and compared with 18 matched controls.CPT and HPT were significantly increased in patients (7.9°C and 47.5°C) compared with controls (15.9°C and 45.2°C, respectively; p.05). In the range of TGI stimuli that were perceived painful by controls, the patients did not indicate painful sensations, thereby indicating a shift of the stimulus-response curve of TGI pain perception toward higher stimulus intensities, that is, greater temperature differentials between cold and warm bars (11.5°C for controls, 16.7°C for patients). The patients rated the pain intensity perceived at the respective pain thresholds (CPT and HPT) in tendency higher than did the controls, whereas they perceived the TGI less painful despite increased stimulus intensities. Unpleasantness ratings were similar between groups.CPT, HPT and temperature differentials for the perception of the TGI, were increased in patients with MDD as compared with controls. Pain intensity, however, was rated differently for CPT and HPT, where patients indicated higher ratings in tendency, and for the TGI stimulation, where pain was perceived less intense.

Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants’ attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects, congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing.