Cold Pain Thresholds Research Articles

Pain and masochistic behaviour: The role of descending modulation.

The mechanisms of pain perception in individuals with masochistic behaviour (MB) remain poorly documented. We hypothesized that MB is associated with context-specific changes in descending pain modulation. We compared the effects of four standardized sets of images with positive (erotic), negative (mutilations), masochistic or neutral emotional valences on the RIII nociceptive reflex evoked by electrical stimulation of the sural nerve and recorded on the ipsilateral biceps femoris in 15 controls and 15 men routinely engaging in MB. We systematically assessed the RIII reflex threshold and recruitment curves (up to the tolerance threshold), thermal (heat and cold) pain thresholds measured on the upper and lower limbs and responses to the pain sensitivity questionnaire, to compare basal pain perception between our two groups of participants. We also assessed anxiety, depression, empathy, alexithymia, high sensation seeking and catastrophizing, to investigate their potential influence on the emotional modulation of pain. Thermal pain thresholds, RIII reflex recruitment curves, and responses to the psychological and pain sensitivity questionnaires were similar in the two groups. Neutral, positive and negative images modulated the RIII reflex similarly in the two groups. By contrast, masochistic images induced a significant (p< 0.01) decrease in RIII reflex responses in subjects with MB, whereas it tended to increase these responses in control subjects. Our data suggest that psychological profile, basal pain sensitivity and the emotional modulation of pain are normal in individuals with MB but that these subjects selectively engage descending pain inhibition in the masochistic context. Decrease pain perception related to masochistic behaviours is associated with specific activation of descending pain inhibition.

Somatosensory and trigeminal pathway abnormalities in Chinese patients with trigeminal neuralgia.

This study aimed to evaluate somatosensory function in Chinese patients with trigeminal neuralgia (TN) using a standard quantitative sensory testing (QST) battery and electrophysiological tests consisting of contact heat-evoked potentials (CHEPs) and blink reflex (BR). Twenty patients with TN and 20 sex- and age-matched healthy controls were recruited for this study. A standard QST protocol recommended by the German Research Network on Neuropathic Pain was carried out on the patients' painful and contralateral faces, the controls' right faces, and all participants' right hands. The CHEPs and BR were recorded at the Cz electrode and bilateral lower bellies of the orbicularis oculi, respectively, with thermal stimuli applied to both sides of the patient's face and the control's right face. The cold detection threshold, heat pain threshold, and mechanical pain threshold on the painful face were lower than those of healthy controls (P < 0.05), whereas the cold pain threshold and mechanical detection threshold were higher (P < 0.05) on the painful faces than those of the contralateral faces from patients or healthy controls. Mechanical pain sensitivity was higher in both test sites than in healthy controls (P < 0.05). Significantly longer N latencies (P < 0.05) and lower N-P amplitudes (P < 0.01) were detected in the patients' painful sites than in the contralateral sites and those of healthy controls. Comprehensive somatosensory abnormalities were found in painful facial sites in patients with TN, suggesting disturbances in the processing of somatosensory stimuli. Deficiencies in electrophysiological tests further revealed unilaterally impaired function of the trigeminal pathway in TN patients.

Effects of High-Definition Transcranial Direct Current Stimulation Targeting the Anterior Cingulate Cortex on the Pain Thresholds: A Randomized Controlled Trial.

The majority of existing clinical studies used active transcranial direct current stimulation (tDCS) over superficial areas of the pain neuromatrix to regulate pain, with conflicting results. Few studies have investigated the effect of tDCS on pain thresholds by focusing on targets in deep parts of the pain neuromatrix. This study applied a single session of high-definition tDCS (HD-tDCS) targeting the anterior cingulate cortex (ACC) and used a parallel and sham-controlled design to compare the antinociceptive effects in healthy individuals by assessing changes in pain thresholds. Sixty-six female individuals (mean age, 20.5 ± 2.4 years) were randomly allocated into the anodal, cathodal, or sham HD-tDCS groups. The primary outcome of the study was pain thresholds (pressure pain threshold, heat pain threshold, and cold pain threshold), which were evaluated before and after stimulation through the use of quantitative sensory tests. Only cathodal HD-tDCS targeting the ACC significantly increased heat pain threshold (P < 0.05) and pressure pain threshold (P < 0.01) in healthy individuals compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain threshold. Furthermore, no statistically significant difference was found in pain thresholds between anodal and sham HD-tDCS (P > 0.38). Independent of HD-tDCS protocols, the positive and negative affective schedule scores were decreased immediately after stimulation compared with baseline. The present study has found that cathodal HD-tDCS targeting the ACC provided a strong antinociceptive effect (increase in pain threshold), demonstrating a positive biological effect of HD-tDCS.

Test-Retest reliability and concurrent validity of novel nerve testing device for thermal detection and thermal pain thresholds

Thermal threshold testing is important for evaluating the thermal function of small-fibre nerve types C and A-delta. This study investigated the reliability and validity of a novel nerve testing device (NNTD) in evaluating thermal detection and thermal pain thresholds. Test-retest reliability of the NNTD and its concurrent validity compared to the current technology (Medoc TSA-2, Advanced Thermosensory Stimulator, Israel) were investigated among 10 healthy participants. Each participant was tested for the warm detection threshold (WDT), cold detection threshold (CDT), hot pain threshold (HPT) and cold pain threshold (CPT) on the medial forearm with NNTD for two trials and the Medoc TSA-2 for one trial over two consecutive days. Intraclass Correlation Coefficient values, Standard Error of Measurement and Bland Altman plots were calculated for test-retest reliability. One-way ANOVA and Bland Altman plots were calculated for validity. The test-retest reliability of the NNTD was good for CPT (ICC = 0.88), moderate for WDT (ICC = 0.545) and HPT (ICC = 0.710). The NNTD was valid for both trials of HPT and CPT and one trial for WDT compared to the Medoc TSA-2. In conclusion, the NNTD showed good to moderate reliability and was found to be valid compared to the Medoc TSA-2.

Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?

The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain. We hypothesized that the TGIP would be increased in comparison with controls in patients with fibromyalgia or irritable bowel syndrome, which are regarded as typical "nociplastic" primary pain syndromes related to changes in central pain processing. We compared the sensations elicited by a large range of combinations of temperature differentials between the warm and cold bars of a thermal grill applied to the hand between patients with fibromyalgia (n = 30) or irritable bowel syndrome (n= 30) and controls (n = 30). The percentage of TGIP responses and the intensity and unpleasantness of TGIP were significantly greater in patients than controls. Furthermore, positive correlations were found between TGIP intensity and clinical pain intensity and between TGIP intensity and the cold pain threshold measured on the hand. These results are consistent with our working hypothesis of shared mechanisms between TGIP and clinical pain mechanisms in patients with nociplastic chronic pain syndromes and suggest that TGIP might represent a clinical marker of central sensitization in these patients.

Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation.

Persistent pain despite satisfactory disease treatment is frequent in rheumatoid arthritis (RA) and spondyloarthritis (Spa) and may result from specific changes in central pain processing. We assessed these mechanisms further by systematically comparing thermal pain thresholds and conditioned pain modulation (CPM) between patients with active RA or Spa and healthy controls. We included 50 patients with RA and 50 patients with Spa and 100 age-matched and sex-matched controls. Heat and cold pain thresholds (HPT-CPT) were measured on the dominant forearm, and CPM was assessed by applying conditioning stimuli (immersion in a cold-water bath) to one foot and the nondominant hand in 2 successive randomized sequences. Descending pain modulation was assessed as the difference in HPTs (in °C) before and after conditioning. Larger HPT differences (ie, a larger CPM effect) reflected more efficient descending inhibition. Potential associations between changes in CPM and clinical data, including disease activity, pain intensity, and psychological and functional variables, were systematically assessed. Heat pain threshold and cold pain threshold were similar in patients and controls. The mean CPM effect was significantly weaker in patients than that in controls for conditioning applied to either the foot (0.25°C ±2.57 vs 2.79°C ±2.31; P < 0.001) or the nondominant hand (0.57°C ±2.74 vs 2.68°C ±2.12; P < 0.001). The smaller CPM effect in patients was correlated with average pain intensity, but not with disease activity or other clinical characteristics, suggesting a significant pathophysiological role for changes in endogenous pain modulation in the mechanisms of chronic pain associated with inflammatory rheumatism.

The Effects of Resistin Gene Polymorphism on Pain Thresholds and Postoperative Sufentanil Consumption in Gastric Cancer Patients.

PurposeAs an adipocyte-secreted hormone, resistin is linked to inflammation, insulin resistance and atherosclerosis. Currently, resistin is proposed as a novel biomarker for postoperative pain intensity. However, due to the various types of surgery and limited numbers of studies, previous conclusions should be validated. This study aimed to explore the effect of resistin polymorphism (rs3745367) on pain thresholds and sufentanil consumption in gastric cancer patients.Patients and MethodsA total of 148 gastric cancer patients enrolled in this study had their pain thresholds measured before surgery. After the exclusion of 16 patients, the characteristics of demography and clinic, numerical rating scale (NRS) and sufentanil consumption of 132 patients were recorded. Rs3745367 of resistin was identified by Sanger sequencing. Multivariate linear regression analysis was performed for sufentanil consumption and mechanical pain threshold.ResultsThe distributions of the GG, AG, and AA genotypes of rs3745367 among the participants were 54 (40.9%), 65 (49.2%), and 13 (9.9%), respectively. The mechanical pain threshold (P=0.04) and postoperative sufentanil consumption in the 1st 24 h (P=0.03) were significantly different among GG, AG, and AA genotype carriers. There was no significant difference among the three genotypes for the heat pain threshold and cold pain threshold. Regarding the NRS, no statistically significant difference among the three different genotypes was found 24 h postoperatively.ConclusionRs3745367 of resistin is associated with the mechanical pain threshold and postoperative sufentanil consumption in gastric cancer patients. Patients with the AA genotype of rs3745367 present an increased mechanical pain threshold and decreased postoperative sufentanil consumption.

Somatosensory Profiles Differentiate Pain and Psychophysiological Symptoms Among Young Adults With Irritable Bowel Syndrome: A Cluster Analysis.

The aim of this study was to investigate if somatosensory profiles can differentiate pain and psychophysiological symptoms among young adults with irritable bowel syndrome (IBS). We performed a cluster analysis of data collected from a randomized clinical trial of 80 IBS patients and 21 age-matched healthy controls (HCs) to stratify pain and symptoms among young adults with IBS by their peripheral sensory profiles. Data of quantitative sensory testing and IBS-related pain and symptoms were collected at baseline and 6-week and 12-week follow-ups. Using the K-means method, IBS patients were classified into 2 clusters, the "IBS normal threshold" (IBS-NT) and the "IBS increased threshold" (IBS-IT). The IBS-NT cluster had a similar pain threshold as the HCs, and the IBS-IT cluster had an increased threshold of somatic pain perception (lower cold pain threshold, higher heat pain threshold, and higher pressure pain threshold, all P<0.001) than HCs. Compared with the IBS-NT cluster, the IBS-IT cluster reported higher levels of IBS-related pain intensity, anxiety, fatigue, and sleep disturbance over the 3 visits (all P<0.05). Young adults with IBS fell into 2 clusters, one with a similar sensory threshold as the HCs and another with an increased pain threshold, who reported higher pain intensity and more severe symptoms. Somatic sensory profiles should be integrated into further personalized self-management intervention among patients with IBS.

Huangqi Guizhi Wuwu Decoction can prevent and treat oxaliplatin-induced neuropathic pain by TNFα/IL-1β/IL-6/MAPK/NF-kB pathway

Objective: This study explored the effects and mechanisms of Huangqi Guizhi Wuwu Decoction on chemotherapy-induced neuropathic pain (CINP).Methods: Bodyweight and related behavioral testing of the rat model were utilized to investigate the effects of Huangqi Guizhi Wuwu Decoction on CINP. ELISA was used to measure the levels of TNF-α, IL-1β, and IL-6, in the serum of chronic CINP rats. Immunohistochemistry and Western blot analysis were performed to detect the expression of MAPK pathway related-proteins namely ERK1/2, p38, and JNK, and the expression of downstream essential proteins such as c-Fos, CREB, and NF-κB.Results: Body weight and related behavioral testing of the rat model suggests that Huangqi Guizhi Wuwu Decoction can improve the slow weight gain of oxaliplatin-induced chronic CINP model rats and effectively prevent and treat oxaliplatin-induced regular CIPN rat model of hyperalgesia. It can also oppress the mechanical pain threshold, cold pain threshold, and heat pain threshold decreased. Furthermore, by ELISA, immunohistochemistry, and western blot analysis, we found that Huangqi Guizhi Wuwu Decoction can down-regulate the levels of TNF-α, IL-1β, and IL-6 in the serum of chronic CINP rats induced by oxaliplatin. It also suppresses the expression of MAPK pathway related-proteins ERK1/2, p38, and JNK. This results in a decrease in the expression of downstream essential proteins, c-Fos, CREB, and Nf-κB.Conclusions: In conclusion, we found that Huangqi Guizhi Wuwu Decoction can combat nerve cell injury, reduce pain sensitization, and prevent and repair the damage of nerve cells in the oxaliplatin CINP model rats via TNFα/IL-1β/IL-6/MAPK/NF-kB pathway.

The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study.

BackgroundThere is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner’s corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN.Patients and MethodsReflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison.ResultsIn controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner’s corpuscle density was correlated with mechanical detection (ρ = −0.51), warm detection (ρ = −0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001).ConclusionsThe findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

Association between pelvic pain bothersomeness and pain sensitivity: A community-based cross-sectional study of young adult females in the Raine Study.

Pelvic pain has been associated with augmented nociceptive processing, but large studies controlling for multiple potential confounding factors are lacking. This study investigated the association between pelvic pain bothersomeness and pain sensitivity in young adult women, accounting for potential confounding factors. Cross-sectional study. Community-dwelling sample. The Raine Study Gen2-22 year follow-up (n=475). The experience of bothersomeness related to pelvic pain was determined from a question in the Urogenital Distress Inventory short form. Pain sensitivity was measured using pressure pain and cold pain thresholds. Potential confounding factors included ethnicity, marital status, highest level of education, income, waist-hip ratio, level of activity, sleep quality, smoking, comorbidity history, C-reactive protein level, musculoskeletal pain experience and psychological distress. Three hundred and sixty-two women (76.2%) reported no pelvic pain bothersomeness, 74 (15.6%) reported mild pelvic pain bothersomeness and 39 (8.2%) reported moderate-severe pelvic pain bothersomeness. After adjusting for marital status (and test site), moderate-severe pelvic pain bothersomeness was associated with a lower pressure pain threshold (i.e. greater pressure pain sensitivity) (coefficient -51.46, 95%CI -98.06 to -4.86, p=0.030). After adjusting for smoking, moderate-severe pelvic pain bothersomeness was also associated with a higher cold pain threshold (i.e. greater cold pain sensitivity) (coefficient 4.35, 95%CI 0.90-7.79, p=0.014). This study suggests augmented nociceptive processing as a contributing factor in pelvic pain bothersomeness for some women. Thorough assessment of women who present clinically with pelvic pain should consider pain sensitivity as a potential contributing factor to their presentation.

Acute tryptophan depletion alters affective touch perception

RationaleAffiliative tactile interactions help regulate physiological arousal and confer resilience to acute and chronic stress. C-tactile afferents (CTs) are a population of unmyelinated, low threshold mechanosensitive cutaneous nerve fibres which respond optimally to a low force stimulus, moving at between 1 and 10 cm/s. As CT firing frequencies correlate positively with subjective ratings of touch pleasantness, they are hypothesised to form the first stage of encoding affiliative tactile interactions. Serotonin is a key modulator of social responses with known effects on bonding.ObjectivesThe aim of the present study was to determine the effect of acutely lowering central serotonin levels on perceptions of CT-targeted affective touch.MethodsIn a double blind, placebo-controlled design, the effect of acute tryptophan depletion (ATD) on 25 female participants’ ratings of directly and vicariously experienced touch was investigated. Psychophysical techniques were used to deliver dynamic tactile stimuli; some velocities were targeted to optimally activate CTs (1–10 cm/s), whereas other, faster and slower strokes fell outside the CT optimal range. Discriminative tactile function, cold pain threshold and tolerance were also measured.ResultsATD significantly increased pleasantness ratings of both directly and vicariously experienced affective touch, increasing discrimination of the specific hedonic value of CT targeted velocities. While ATD had no effect on either tactile or cold pain thresholds, there was a trend for reduced tolerance to cold pain.ConclusionsThese findings are consistent with previous reports that depletion of central serotonin levels modulates neural and behavioural responsiveness to appetitive sensory signals.

Time Course and Risk Profile of Work-Related Neck Disability: A Longitudinal Latent Class Growth Analysis

ObjectiveGiven the economic burden of work-related neck pain and disability, it is important to understand its time course and associated risk factors to direct better management strategies. This study aimed to identify the 1-year trajectories of work-related neck disability in a high-risk occupation group such as sonography and to investigate which baseline biopsychosocial factors are associated with the identified trajectories.MethodsA longitudinal study was conducted among 92 sonographers with neck disability assessed at 3 time points—baseline, 6 months, and 12 months—using the Neck Disability Index. Baseline biopsychosocial measures included individual characteristics (demographics and physical activity levels), work-related physical and psychosocial factors (eg, ergonomic risk, workplace social support, job satisfaction), general psychological features (depression, anxiety, pain catastrophizing, and fear-avoidance beliefs), and quantitative sensory testing of somatosensory function (cold and pressure pain thresholds at neck and tibialis anterior, and temporal summation).ResultsTwo distinct trajectories of neck disability were identified, including a “low-resolving disability” trajectory showing slow improvement toward no disability (64.8%) and a “moderate-fluctuating disability” trajectory characterized by persistent moderate disability with a small fluctuation across time (35.2%). The trajectory of moderate-fluctuating disability was associated with more severe symptoms, lower vigorous physical activity, higher ergonomic risk, remote cold hyperalgesia, widespread mechanical hyperalgesia, heightened pain facilitation, and several psychosocial factors such as anxiety, depression, lower job satisfaction, and lower workplace social support at baseline.ConclusionOver one-third of sonographers were at risk of developing a moderate-fluctuating disability trajectory. This unfavorable trajectory was associated with low physical activity level, poor ergonomics, psychosocial distress, and central sensitization at baseline.ImpactThis study has important implications for the management of neck disability in workers. Addressing modifiable factors including low vigorous physical activity, poor ergonomics, anxiety, depression, and lack of workplace social support may improve the trajectory of work-related neck disability.

Pain sensitivities predict prophylactic treatment outcomes of flunarizine in chronic migraine patients: A prospective study.

We aimed to assess the differences in quantitative sensory testing between chronic migraine and healthy controls and to explore the association between pain sensitivities and outcomes in chronic migraine following preventive treatment. In this prospective open-label study, preventive-naïve chronic migraine and healthy controls were recruited, and cold, heat, mechanical punctate, and pressure pain thresholds over the dermatomes of first branch of trigeminal nerve and first thoracic nerve were measured by quantitative sensory testing at baseline. Chronic migraines were treated with flunarizine and treatment response was defined as ≥50% reduction in the number of monthly headache days over the 12-week treatment period. Eighty-four chronic migraines and fifty age-and-sex-matched healthy controls were included in the analysis. The chronic migraine had higher cold pain thresholds over the dermatomes of the first branch of trigeminal nerve and the first thoracic nerve (p < 0.001 and < 0.001), lower pressure pain thresholds over the dermatomes of the first thoracic nerve (p = 0.003), heat pain thresholds over the dermatomes of the first branch of the trigeminal nerve and the first thoracic nerve (p < 0.001 and p = 0.015) than healthy controls. After treatment, 24/84 chronic migraine had treatment response. The responders with relatively normal pain sensitivity had higher heat pain thresholds over the dermatome of the first branch of the trigeminal nerve (p = 0.002), mechanical punctate pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.023), and pressure pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.026) than the hypersensitive non-responders. Decision tree analysis showed that patients with mechanical punctate pain threshold over the dermatomes of the first branch of the trigeminal nerve > 158 g (p = 0.020) or heat pain threshold over the dermatome of the first branch of the trigeminal nerve > 44.9°C (p = 0.002) were more likely to be responders. Chronic migraine were generally more sensitive compared to healthy controls. Preventive treatment with flunarizine should be recommended particularly for chronic migraine who have relatively normal sensitivity to mechanical punctate or heat pain.Trial registration: This study was registered on ClinicalTrials.gov (Identifier: NCT02747940).

Dissecting central post-stroke pain: a controlled symptom-psychophysical characterization.

Central post-stroke pain affects up to 12% of stroke survivors and is notoriously refractory to treatment. However, stroke patients often suffer from other types of pain of non-neuropathic nature (musculoskeletal, inflammatory, complex regional) and no head-to-head comparison of their respective clinical and somatosensory profiles has been performed so far. We compared 39 patients with definite central neuropathic post-stroke pain with two matched control groups: 32 patients with exclusively non-neuropathic pain developed after stroke and 31 stroke patients not complaining of pain. Patients underwent deep phenotyping via a comprehensive assessment including clinical exam, questionnaires and quantitative sensory testing to dissect central post-stroke pain from chronic pain in general and stroke. While central post-stroke pain was mostly located in the face and limbs, non-neuropathic pain was predominantly axial and located in neck, shoulders and knees (P < 0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%, n = 32, P < 0.001), tingling (66.7%, n = 26, P < 0.001) and evoked by cold (64.1%, n = 25, P < 0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group (P < 0.001), which also presented higher levels of deafferentation (P < 0.012) with more asymmetric cold and warm detection thresholds compared with controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was <41% of the contralateral threshold) odds ratio (OR) was 12 (95% CI: 3.8–41.6) for neuropathic pain. Additionally, cold detection threshold/warm detection threshold ratio correlated with the presence of neuropathic pain (ρ = −0.4, P < 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold (ρ = −0.4; P = 0.008) and heat pain thresholds (ρ = 0.5; P = 0.003), burning pain with mechanical detection (ρ = −0.4; P = 0.015) and mechanical pain thresholds (ρ = −0.4, P < 0.013), evoked pain with mechanical pain threshold (ρ = −0.3; P = 0.047). Logistic regression showed that the combination of cold hypoesthesia on quantitative sensory testing, the Neuropathic Pain Symptom Inventory, and the allodynia intensity on bedside examination explained 77% of the occurrence of neuropathic pain. These findings provide insights into the clinical-psychophysics relationships in central post-stroke pain and may assist more precise distinction of neuropathic from non-neuropathic post-stroke pain in clinical practice and in future trials.

Identifying Patients at High Risk of Chronic Pain After Video-Assisted Thoracoscopic Surgery Using Thermal Quantitative Sensory Testing

To examine whether perioperative thermal quantitative sensory testing could be used to identify patients at high risk of chronic pain after video-assisted thoracoscopic surgery (VATS). A single-center, prospective, observational study. At the Peking University People's Hospital. A total of 111 patients scheduled to undergo VATS were enrolled. Quantitative sensory testing was conducted at the anterior intercostal incision prior to surgery and after chest tube removal. The patient's chronic pain was assessed at 3 months after surgery using a questionnaire. The incidence of chronic pain was 35 out of 107 evaluable patients (32.7%). Among the 35 patients with chronic pain, 26 had features characteristic of neuropathic pain (74.3%). Compared to the patients without chronic pain, subjects with chronic pain had a significantly greater perioperative change in cold pain threshold (CPT; p=0.032), but not cold detection threshold, warm detection threshold, and hot pain threshold . In the multivariate regression, perioperative CPT change was associated with chronic pain after VATS (odds ratio=1.043, p=0.026). Chronic pain after VATS is typically neuropathic. The change in perioperative CPT at the incision site may help to identify patients at higher risk of chronic pain after VATS.

Effects of High-Definition Transcranial Direct Current Stimulation Over the Primary Motor Cortex on Cold Pain Sensitivity Among Healthy Adults.

Some clinical studies have shown promising effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on pain relief. Nevertheless, a few studies reported no significant analgesic effects of tDCS, likely due to the complexity of clinical pain conditions. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds that are present in the clinical data. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) stimulation over M1 on sensitivity to experimental pain and assess whether these effects could be influenced by the pain-related cognitions and emotions. A randomized, double-blinded, crossover, and sham-controlled design was adopted. A total of 28 healthy participants received anodal, cathodal, or sham HD-tDCS over M1 (1 mA for 20 min) in different sessions, in which montage has the advantage of producing more focal stimulation. Using a cold pressor test, several indices reflecting the sensitivity to cold pain were measured immediately after HD-tDCS stimulation, such as cold pain threshold and tolerance and cold pain intensity and unpleasantness ratings. Results showed that only anodal HD-tDCS significantly increased cold pain threshold when compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain tolerance, pain intensity, and unpleasantness ratings. Correlation analysis revealed that individuals that a had lower level of attentional bias to negative information benefited more from attenuating pain intensity rating induced by anodal HD-tDCS. Therefore, single-session anodal HD-tDCS modulates the sensory-discriminative aspect of pain perception as indexed by the increased pain threshold. In addition, the modulating effects of HD-tDCS on attenuating pain intensity to suprathreshold pain could be influenced by the participant’s negative attentional bias, which deserves to be taken into consideration in the clinical applications.

The Diurnal Profile of Human Basal Pain Sensitivity and Skin Sympathetic Nerve Activity: A Healthy Volunteer Study.

ObjectiveThe diurnal rhythm profile of human basal pain sensitivity and its association with sympathetic nerve activity are not fully understood. This study aimed to examine rhythmic changes in experimental pain sensitivity and skin sympathetic nerve activity in healthy volunteers.MethodsThirty healthy volunteers were included in the study. Experimental pain sensitivity, including pressure pain threshold and tolerance, cold pain threshold (CPT) and tolerance, skin sympathetic nerve activity, and cardiovascular parameters (including heart rate, cardiac output, and peripheral vascular resistance) at six time points throughout the day (08:00, 12:00, 16:00, 20:00, 00:00, and 04:00) were sequentially measured. Circadian rhythm analysis was performed on the mean values of the different measurements and individual subjects.ResultsSignificant differences were found in experimental pain sensitivity, skin sympathetic nerve activity, and non-invasive cardiovascular parameters at different time points (P < 0.05). The minimum measured values of all four types of experimental pain sensitivity were consistently observed at 04:00. Rhythmical analysis showed that the mean values of pressure pain threshold (meta2d P = 0.016) and skin sympathetic nerve activity (meta2d P = 0.039) were significant. Significant diurnal rhythms in pain sensitivity and skin sympathetic nerve activity existed in some individuals but not in others. No significant correlation between experimental pain sensitivity and skin sympathetic nerve activity was found at any time point (P > 0.05).ConclusionSignificant diurnal fluctuations were observed in different pain sensitivities and skin sympathetic nerve activity. No significant correlation between experimental pain sensitivity and sympathetic excitability at different times was found; the reasons for these phenomena remain to be further studied.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2000039709].

Psychosocial and Sensory Factors Contribute to Self-Reported Pain and Quality of Life in Young Adults with Irritable Bowel Syndrome

AimsPsychosocial and sensory factors, including anxiety, depression, and pressure pain threshold have been used to cluster chronic symptoms in irritable bowel syndrome (IBS). This study examined the contribution of psychosocial sensory factors on pain interference and quality of life (QOL) in this population. DesignWe performed a cross-sectional analysis of baseline data from a randomized controlled trial. SettingsTwo gastrointestinal clinics, general communities, and two large campuses of a public university in the Northeastern United States. Participants/SubjectsEighty young adults with IBS aged 21 ± 2.57 years (76.25% female). MethodsDemographic and psychosocial factors including anxiety, depression, fatigue, cognition or general concerns, sleep disturbance, self-efficacy, coping, and food intake were measured as independent variables. Quantitative sensory testing was conducted to measure mechanical, thermal, and pressure pain thresholds. Self-reported pain measured by the brief pain inventory (BPI) and IBS-QOL were assessed as the outcome variables. Regression analysis and mediation analysis were conducted to determine the associated factors of IBS pain and QOL. ResultsAge, sex, and psychosocial factors including coping, self-efficacy, alcohol intake, mechanical pain sensitivity, and cold pain threshold were significantly associated with pain interference (all p < 0.05). Coping, and self-efficacy were significantly associated with IBS-QOL (all p < 0.05). In the mediation analysis, coping catastrophizing and self-efficacy were indirectly associated with IBS-QOL mediated by fatigue. ConclusionsPsychosocial factors including coping and self-efficacy, and quantitative sensory testing factors significantly correlate with self-reported pain and QOL among young adults with IBS. This preliminary research calls for further interventional studies that target personalized psychosocial and quantitative sensory factors to improve pain management and quality of life in IBS patients.

New diagnostic measures of oxaliplatin-induced peripheral sensory neuropathy

ObjectiveOxaliplatin-induced peripheral neuropathy (OIPN) is an unwanted side effect of oxaliplatin chemotherapy treatment. OIPN manifests in an acute phase that lasts a few days after injection and a persistent phase that may become chronic. Currently, there is no consensus about a clinically applicable, quantitative, and objective measure of OIPN. MethodsSeventeen patients treated with oxaliplatin containing adjuvant chemotherapy for stage III colon cancer, but otherwise healthy, were tested with six quantitative sensory tests (QST) and five large fibre perception threshold tracking (PTT) measures (quantified by, e.g., rheobase and electrotonus threshold) one hour before each of the 12 chemotherapy cycles given at two weeks’ intervals. These measures were repeated at 3, 6, and 12-month follow-ups. The temporal development of OIPN assessed by the Common Terminology Criteria for Adverse Events (CTCAE) scale, QST, and PTT measures was calculated by linear regression. ResultsThe CTCAE score showed a tri-phasic increase during the treatment and remained increased during the follow-up. The vibration threshold (R = 0.25, p<0.001), the cold pain threshold (R = 0.17, p = 0.02), and the rheobase (R = 0.28, p < 0.001) increased during treatment, whereas the cold detection threshold (R=-0.16, p = 0.002) decreased. The cold pain threshold and the rheobase remained increased, and the cold detection and heat pain threshold remained decreased during follow-up. ConclusionsIncreased cold pain sensitivity and decreased large fibre sensitivity (increased rheobase) correlate to the persistent OIPN, whereas the CTCAE score assesses both acute and persistent OIPN. Furthermore, the novel PTT method assessed the nerve excitability changes caused by the oxaliplatin.