The role of voltage-gated calcium channel α2δ-1 in the occurrence and development in myofascial orofacial pain.

Patients who suffer from myofascial orofacial pain could affect their quality of life deeply. The pathogenesis of pain is still unclear. Our objective was to assess Whether Voltage-gated calcium channel α2δ-1(Cavα2δ-1) is related to myofascial orofacial pain. Rats were divided into the masseter tendon ligation group and the sham group. Compared with the sham group, the mechanical pain threshold of the masseter tendon ligation group was reduced on the 4th, 7th, 10th and 14th day after operation(P < 0.05). On the 14th day after operation, Cavα2δ-1 mRNA expression levels in trigeminal ganglion (TG) and the trigeminal spinal subnucleus caudalis and C1-C2 spinal cervical dorsal horn (Vc/C2) of the masseter tendon ligation group were increased (PTG=0.021, PVc/C2=0.012). Rats were divided into three groups. On the 4th day after ligating the superficial tendon of the left masseter muscle of the rats, 10 ul Cavα2δ-1 antisense oligonucleotide, 10 ul Cavα2δ-1 mismatched oligonucleotides and 10 ul normal saline was separately injected into the left masseter muscle of rats in Cavα2δ-1 antisense oligonucleotide group, Cavα2δ-1 mismatched oligonucleotides group and normal saline control group twice a day for 4 days. The mechanical pain threshold of the Cavα2δ-1 antisense oligonucleotides group was higher than Cavα2δ-1 mismatched oligonucleotides group on the 7th and 10th day after operation (P < 0.01). After PC12 cells were treated with lipopolysaccharide, Cavα2δ-1 mRNA expression level increased (P < 0.001). Cavα2δ-1 may be involved in the occurrence and development in myofascial orofacial pain.

Contribution of mechanoreceptors to spinal cord injury-induced mechanical allodynia.

ABSTRACT: Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown to reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim of the present study was to understand the contribution of mechanoreceptors with respect to mechanical allodynia in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B expressing mechanoreceptors before SCI, mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. Peptidergic nociceptor sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. However, skin-nerve preparations of contusion SCI mice 7 days after injury yielded hyperexcitability in nociceptors, not in mechanoreceptors, which makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors seem to be the main drivers of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early-onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.

Associations between pain intensity, pain sensitivity, demographics, psychological factors, disability, physical activity, pain phenotype and COVID-19 history in low back pain: An observational study.

BACKGROUND AND PURPOSE: Knowledge of the factors affecting pain intensity and pain sensitivity can inform treatment targets and strategies aimed at personalizing the intervention, conceivably increasing its positive impact on patients. Therefore, this study aimed to investigate the association between demographic factors (sex and age), body mass index (BMI), psychological factors (anxiety and depression, kinesiophobia and catastrophizing), self-reported physical activity, pain phenotype (symptoms of central sensitization, and nociceptive or neuropathic pain), history of COVID-19 and pain intensity and sensitivity in patients with chronic non-specific low back pain (LBP). METHODS: This was a cross-sectional secondary analysis with 83 participants with chronic non-specific LBP recruited from the community between August 2021 and April 2022. BMI, pain intensity (Visual Analog Scale), pain sensitivity at the lower back and at a distant point [pressure pain threshold], catastrophizing (Pain Catastrophizing Scale), kinesiophobia (Tampa Scale for Kinesiophobia), anxiety and depression (Hospital Anxiety and Depression Scale), pain phenotype (Central Sensitization Inventory and PainDetect Questionnaire), physical activity (International Physical Activity Questionnaire), and disability (Roland Morris Disability Questionnaire) were assessed. Multiple linear regression analyses with pain intensity and sensitivity as the dependent variables were used. RESULTS: The model for pain intensity explained 34% of its variance (Adjusted R2 = -0.343, p < 0.001), with depression and anxiety (p = 0.008) and disability (p = 0.035) reaching statistical significance. The model for pain sensitivity at the lower back, also explained 34% of its variance (Adjusted R2 = 0.344, p < 0.001) at the lower back with sex, BMI, and kinesiophobia reaching statistical significance (p < 0.05) and 15% of the variance at a distant body site (Adjusted R2 = 0.148, p = 0.018) with sex and BMI reaching statistical significance (p < 0.05). DISCUSSION: This study found that different factors are associated with pain intensity and pain sensitivity in individuals with LBP. Increased pain intensity was associated with higher levels of anxiety and depression and disability and increased pain sensitivity was associated with being a female, higher kinesiophobia, and lower BMI.

Quality of life, craniomandibular function, and psychosocial factors related to pain and movement in patients with head and neck cancer.

PURPOSE: To describe the characteristics of and the associations between health-related quality of life, pain, craniomandibular function, and psychosocial factors related to pain and fear of movement in patients with head and neck cancer. METHODS: Seventy-eight patients diagnosed with HNC were recruited. Measurements of the maximum mouth opening range and pressure pain thresholds on the masseter muscle and the distal phalanx of the thumb were conducted, as well as a battery of self-report questionnaires were administrated, including the QoL Questionnaire (EORT QLQ-H&N35), Numeric Rating Scale (NRS), Pain Catastrophizing Scale (PCS), the Spanish translation of the Tampa Scale for Kinesiophobia for Temporomandibular Disorders (TSK-TMD), and the short version of the Craniofacial Pain and Disability Inventory (CF-PDI-11). RESULTS: The study sample (66.7% men, mean age 60.12 [11.95] years) experienced a moderate impact on their QoL levels (57.68 [18.25] EORT QLQ-H&N35) and high kinesiophobia values (20.49 [9.11] TSK-TMD). Pain was present in 41% of the patients, but only 3.8% reported severe pain. 26.4% had a restricted mouth opening range, and 34.62% showed significant catastrophism levels. There were strong positive correlations between EORT QLQ-H&N35 and CF-PDI-11 (r = 0.81), between NRS and CF-PDI-11 (r = 0.74), and between PCS and CF-PDI-11 (r = 0.66). CONCLUSION: Patients with HNC experience negative effects in their QoL, related to their impairment in craniomandibular function. Fear of movement, pain intensity, and catastrophism are associated with poorer functionality; relationships that should be considered when attempting to improve health care.

Functional connectivity associated with attention networks differs among subgroups of fibromyalgia patients: an observational case-control study.

Fibromyalgia is a heterogenous chronic pain disorder diagnosed by symptom-based criteria. The aim of this study was to clarify different pathophysiological characteristics between subgroups of patients with fibromyalgia. We identified subgroups with distinct pain thresholds: those with a low pressure pain threshold (PL; 16 patients) and those with a normal pressure pain threshold (PN; 15 patients). Both groups experienced severe pain. We performed resting-state functional MRI analysis and detected 11 functional connectivity pairs among all 164 ROIs with distinct difference between the two groups (p < 0.001). The most distinctive one was that the PN group had significantly higher functional connectivity between the secondary somatosensory area and the dorsal attention network (p < 0.0001). Then, we investigated the transmission pathway of pain stimuli. Functional connectivity of the thalamus to the insular cortex was significantly higher in the PL group (p < 0.01 - 0.05). These results suggest that endogenous pain driven by top-down signals via the dorsal attention network may contribute to pain sensation in a subgroup of fibromyalgia patients with a normal pain threshold. Besides, external pain driven by bottom-up signals via the spinothalamic tract may contribute to pain sensations in another group of patients with a low pain threshold. Trial registration: UMIN000037712.

Influence of psychometric and sleep quality features on painful mechanical sensitivity and pain modulation in patients with temporomandibular disorders.

Investigating the collective impact of psychometric properties and sleep quality on pain sensitivity in temporomandibular disorder (TMD) patients could improve clinical management strategies. OBJECTIVE: Assessing whether combined psychometric properties and sleep quality impact painful mechanical sensitivity and pain modulation in TMD patients. MATERIALS AND METHODS: A cross-sectional study using secondary data analysis of 77 TMD patients and 101 controls. All participants completed questionnaires characterizing their psychometric profile (anxiety, depression, stress and catastrophizing) and sleep quality, alongside psychophysical tests for painful mechanical sensory (mechanical pain threshold (MPT), pressure pain threshold (PPT), and wind-up ratio (WUR)) and conditioned pain modulation (CPM). Participants were grouped into "High distress" or "Low distress" categories based on psychometric properties and sleep quality using hierarchical cluster and k-means analyses. Multiple linear regression evaluated the influence of TMD, age, and the distress cluster on MPT, WUR, PPT, and CPM in masseter and thenar muscles. Differences were statistically significant when p < 0.05. RESULTS: The presence of TMD was the strongest predictor of mechanical painful sensitivity in the trigeminal region (MPT[F(3,174) = 51.902;p < .001;R2 = .463]; TMD presence (ß = -.682) / PPT[F(3,174) = 15.573;p < .001;R2 = .198] TMD presence (ß = -.452), and extra-trigeminal (MPT[F(3,174) = 35.897;p < .001;R2 = .382] TMD (ß = -.647) / CPM [F(3,174) = 4.106;p < .05;R2 = .050] TMD presence (ß = .197). Furthermore, neither the high distress group nor the low distress group were able to significantly influence the variation of the values of any of the psychophysical variables evaluated (p > .05). CONCLUSIONS: There is not a significant influence of impairment clusters based on psychological variables and sleep quality on painful mechanical sensitivity and pain modulation, regardless of the presence of TMD. CLINICAL RELEVANCE: This outcome suggests that psychosocial factors and sleep quality may not play a decisive role in the sensory-discriminative aspect of pain, particularly concerning painful TMD.

The Relationship between Abdominal Diastasis and Lumbar Pain Pressure Threshold in Women Who Have Given Birth between the Ages of 30 and 45 Years-An Observational Pilot Study.

Background and Objectives: Current evidence confirms that the magnitude of the inter-rectus distance (IRD) is associated with the severity of abdominal pain. Furthermore, evidence exists in the literature about the impact abdominal muscles have on low back pain, lumbopelvic pain, breathing and lumbar abdominal strength; however, no studies analysing the level of association between abdominal diastasis and lumbar pain pressure threshold (PPT) exist. The aim of this study was to analyse the level of association between the rectus abdominis distance and pain pressure threshold in the lumbar spinous processes in women who have given birth between the ages of 30 and 45 years. Secondly, it was to study the level of association between the time elapsed since the last delivery and low back pain in women who have given birth between 30 and 45 years of age. Material and Methods: This was a pilot observational study in which 21 females participated. The abdominal diastasis was measured by ultrasound, the pain pressure threshold was assessed by an algometer and the pain perception by the Mc Gill questionnaire. Results: There was no significant relationship between increased abdominal distance and increased lumbopelvic pain in women who gave birth between the ages of 30 and 45 years. However, there was a correlation between the time that had elapsed since the last delivery and low back pain. Conclusions: there was a correlation between the time that had elapsed since the last delivery and low back pain. Further studies analysing factors that may perpetuate the chronicity of symptoms, such as lifestyle and intrinsic factors, are needed.

Is the Central Sensitization Inventory (CSI) associated with quantitative sensory testing (QST)? A systematic review and meta-analysis.

Central sensitization (CS) involves an amplification of neural processing within the central nervous system that can result in widespread pain patterns and hypersensitivity to stimuli. The Central Sensitization Inventory (CSI) and various quantitative sensory testing (QST) methods purport to assess clinical markers of CS. The purpose of this systematic review and meta-analysis was to summarize and quantify the associations between total CSI scores and QST measures from previous studies. A systematic search identified 39 unique studies that were deemed eligible for the systematic review and 33 studies for meta-analyses (with 3314 subjects and 154 effect sizes), including five QST modalities: conditioned pain modulation, temporal summation, pressure pain threshold, heat pain threshold, and cold pain threshold. The meta-analysis yielded statistically significant CSI-QST correlations in total subject samples for all five QST modalities. The strongest associations were identified between CSI scores and pain threshold testing, especially pressure pain threshold, in which 51% of effects sizes, from 29 studies and 3071 subjects, were determined to be in a medium to large range.

Pain symptoms are associated with two-point discrimination threshold in patients with temporomandibular disorders.

OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.

Effects of transcutaneous electrical nerve stimulation on pain, function, and descending inhibition in people with non-specific chronic low-back pain: a study protocol for a randomized crossover trial.

BACKGROUND: Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP. METHODS/DESIGN: This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2-125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05. DISCUSSION: This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.

Exercise induced hypoalgesia during different intensities of a dynamic resistance exercise: A randomized controlled trial.

INTRODUCTION: Exercise produces an immediate lessening of pain sensitivity (Exercise-Induced Hypoalgesia (EIH)) in healthy individuals at local and distant sites, possibly through a shared mechanism with conditioned pain modulation (CPM). Dynamic resistance exercise is a recommended type of exercise to reduce pain, yet limited research has examined the effects of intensity on EIH during this type of exercise. Therefore, the primary purpose of this study is to compare changes in PPT at a local and distant site during a leg extension exercise at a high intensity, a low intensity, or a quiet rest condition. A secondary purpose is to examine if CPM changes after each intervention. The final purpose is to examine if baseline pain sensitivity measures are correlated with response to each intervention. METHODS: In a randomized controlled trial of 60 healthy participants, participants completed baseline pain sensitivity testing (heat pain threshold, temporal summation, a cold pressor test as measure of CPM) and were randomly assigned to complete a knee extension exercise at: 1) high intensity (75% of a 1 Repetition Maximum (RM), 2) low intensity (30% 1RM), or 3) Quiet Rest. PPT was measured between each set at a local (quadriceps) and distant (trapezius) site during the intervention. CPM was then repeated after the intervention. To test the first purpose of the study, a three-way ANOVA examined for time x site x intervention interaction effects. To examine for changes in CPM by group, a mixed-model ANOVA was performed. Finally, a Pearson Correlation examined the association between baseline pain sensitivity and response to each intervention. RESULTS: Time x site x intervention interaction effects were not significant (F(5.3, 150.97) = 0.87, p = 0.51, partial eta2 = 0.03). CPM did not significantly change after the interventions (time x intervention F(1,38) = 0.81, p = 0.37, partial eta2 = 0.02. EIH effects at the quadriceps displayed a significant, positive moderate association with baseline HPT applied over the trapezius (r = 0.61, p<0.01) and TS (r = 0.46, p = 0.04). DISCUSSION: In healthy participants, PPT and CPM did not significantly differ after a leg extension exercise performed at a high intensity, low intensity, or quiet rest condition. It is possible pre-intervention CPM testing with a noxious stimuli may have impaired inhibitory effects frequently observed during exercise but future research would need to examine this hypothesis.

Sex Dimorphism in Pain Threshold and Neuroinflammatory Response: The Protective Effect of Female Sexual Hormones on Behavior and Seizures in an Allergic Rhinitis Model.

Our previous research demonstrated that allergic rhinitis could impact behavior and seizure threshold in male mice. However, due to the complex hormonal cycles and hormonal influences on behavior in female mice, male mice are more commonly used for behavioral tests. In this study, we aimed to determine whether these findings were replicable in female mice and to explore the potential involvement of sexual hormones in regulating neuroinflammation in an allergic model. Our results indicate that pain threshold was decreased in female mice with allergic rhinitis and the levels of IL-23/IL-17A/IL-17R were increased in their Dorsal root ganglia. However, unlike males, female mice with AR did not display neuropsychological symptoms such as learning and memory deficits, depression, and anxiety-like behavior. This was along with decreased levels of DNA methyl transferase 1 (DNMT1) and inflammatory cytokines in their hippocampus. Ovariectomized mice were used to mitigate hormonal effects, and the results showed that they had behavioral changes and neuroinflammation in their hippocampus similar to male mice, as well as increased levels of DNMT1. These findings demonstrate sex differences in how allergic rhinitis affects behavior, pain sensitivity, and seizure thresholds. Furthermore, our data suggest that DNMT1 may be influenced by sexual hormones, which could play a role in modulating inflammation in allergic conditions.

Reliability and measurement error of exercise-induced hypoalgesia in pain-free adults and adults with musculoskeletal pain: A systematic review.

OBJECTIVES: We systematically reviewed the reliability and measurement error of exercise-induced hypoalgesia (EIH) in pain-free adults and in adults with musculoskeletal (MSK) pain. METHODS: We searched EMBASE, PUBMED, SCOPUS, CINAHL, and PSYCINFO from inception to November 2021 (updated in February 2024). In addition, manual searches of the grey literature were conducted in March 2022, September 2023, and February 2024. The inclusion criteria were as follows: adults - pain-free and with MSK pain - a single bout of exercise (any type) combined with experimental pre-post pain tests, and assessment of the reliability and/or measurement error of EIH. Two independent reviewers selected the studies, assessed their Risk of Bias (RoB) with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) RoB tool, and graded the individual results (COSMIN modified Grading of Recommendations Assessment, Development, and Evaluation). RESULTS: We included five studies involving pain-free individuals (n = 168), which were deemed to have an overall "doubtful" RoB. No study including adults with MSK pain was found. The following ranges of parameters of reliability and measurement error of EIH were reported: intraclass correlation coefficients: 0-0.61; kappa: 0.01-0.46; standard error of measurement: 30.1-105 kPa and 10.4-21%; smallest detectable changes: 83.54-291.1 kPa and 28.83-58.21%. CONCLUSIONS: We concluded, with a very low level of certainty, that the reliability and measurement error of EIH is, in pain-free adults, respectively, "insufficient" and "indeterminate." Future studies should focus on people with MSK pain and could consider using tailored exercises, other test modalities than pressure pain threshold, rater/assessor blinding, and strict control of the sources of variations (e.g., participants' expectations).

Conditioned pain modulation (CPM) paradigm type affects its sensitivity as a biomarker of fibromyalgia.

Fibromyalgia (FM) is a widespread chronic pain syndrome, possibly associated with the presence of central dysfunction in descending pain inhibition pathways. Conditioned Pain Modulation (CPM) has been proposed as a biomarker of FM. Nonetheless, the wide variety of methods used to measure CPM has hampered robust conclusions being reached. To clarify the validity of CPM as a biomarker of FM, we tested two CPM paradigms (parallel and sequential) in a sample of 23 female patients and 23 healthy women by applying test (mechanical) stimuli and conditioning (pressure cuff) stimuli. We evaluated whether CPM indices could correctly classify patients and controls, and we also determined the correlations between the indices and clinical variables such as symptomatology, disease impact, depression, quality of life, pain intensity, pain interference, fatigue and numbness. In addition, we compared the clinical status of CPM responders (efficient pain inhibitory mechanism) and non-responders. We observed that only parallel CPM testing correctly classified about 70% of patients with FM. In addition, more than 80% of healthy participants were found to be responders, while the rate was about 50% in the FM patients. The sequential CPM test was not as sensitive, with a decrease of up to 40% in the response rate for both groups. On the other hand, we did not observe any correlation between CPM measures and clinical symptoms. In summary, our findings demonstrate the influence of the CPM paradigm used and confirm that CPM may be a useful marker to complement FM diagnosis. However, the findings also cast doubts on the sensitivity of CPM as a marker of pain severity in FM.

The normative values of pain thresholds in healthy Taiwanese.

OBJECTIVE: Quantitative sensory testing is widely used in clinical and research settings to assess the sensory functions of healthy subjects and patients. It is of importance to establish normative values in a healthy population to provide reference for studies involving patients. Given the absence of normative values for pain thresholds in Taiwan, the aim of this study was to report the normative values for future reference in the Taiwanese population and compare the differences between male and female participants. METHODS: Healthy adults without any chronic or acute pain condition were recruited. The pain thresholds were assessed over the cephalic (supraorbital area and masseter muscle) and extracephalic (medio-volar forearm and thenar eminence) areas. The heat, cold, mechanical punctate, and pressure pain thresholds were measured with a standardized protocol. Comparisons between male and female participants were performed. RESULTS: One hundred and thirty healthy participants (55 males: 30.4 ± 7.4 years; 75 females: 30.5 ± 8.1 years) finished the assessments. Male participants were less sensitive to mechanical stimuli, including pressure over masseter muscle (male vs. female: 178.5 ± 56.7 vs. 156.6 ± 58.4 kPa, p = .034) and punctate over medio-volar forearm (male vs. female: 116.4 ± 45.2 vs. 98.7 ± 65.4 g, p = .011), compared to female participants. However, female participants were less sensitive to cold stimuli, indicated by lower cold pain thresholds over the supraorbital area (male vs. female: 18.6 ± 8.4 vs. 13.6 ± 9.3°C, p = .004), compared to male participants. No significant differences were found between sexes in other pain threshold parameters. CONCLUSIONS: We provided the normative values of healthy male and female adults in Taiwan. This information is crucial for comparison in future pain-related studies to identify potential hypoalgesia or hyperalgesia of tested subjects.

Investigating mortality salience as a potential causal influence and moderator of responses to laboratory pain.

Background: Because pain can have profound ramifications for quality of life and daily functioning, understanding nuances in the interplay of psychosocial experiences with pain perception is vital for effective pain management. In separate lines of research, pain resilience and mortality salience have emerged as potentially important psychological correlates of reduced pain severity and increased tolerance of pain. However, to date, there has been a paucity of research examining potentially interactive effects of these factors on pain perception. To address this gap, the present experiment investigated mortality salience as a causal influence on tolerance of laboratory pain and a moderator of associations between pain resilience and pain tolerance within a Chinese sample. Methods: Participants were healthy young Chinese adults (86 women, 84 men) who first completed a brief initial cold pressor test (CPT) followed by measures of demographics and pain resilience. Subsequently, participants randomly assigned to a mortality salience (MS) condition completed two open-ended essay questions in which they wrote about their death as well as a death anxiety scale while those randomly assigned to a control condition completed analogous tasks about watching television. Finally, all participants engaged in a delay task and a second CPT designed to measure post-manipulation pain tolerance and subjective pain intensity levels. Results: MS condition cohorts showed greater pain tolerance than controls on the post-manipulation CPT, though pain intensity levels did not differ between groups. Moderator analyses indicated that the relationship between the behavior perseverance facet of pain resilience and pain tolerance was significantly stronger among MS condition participants than controls. Conclusions: This experiment is the first to document potential causal effects of MS on pain tolerance and Ms as a moderator of the association between self-reported behavior perseverance and behavioral pain tolerance. Findings provide foundations for extensions within clinical pain samples.

Paradox pain sensitivity using cuff pressure or algometer testing in patients with hemophilia.

INTRODUCTION: Pain is a common comorbidity in patients with hemophilia (PwH) due to hemophilic arthropathy. This study aims to explore pain sensitivity in PwH methodologically investigating in cuff pressure testing compared to algometer testing. METHODS: 37 PwH and 35 healthy control subjects (Con) enrolled in this study. Joint health status was assessed. Subjective pain was evaluated using numeric rating scales. Pain sensitivity was measured with pressure algometry and cuff pressure algometry. Pressure pain thresholds of the algometer (PPTa) were measured at knee, ankle joints, and forehead. Subsequently, thresholds of cuff pressure were measured at the left and right lower legs (PPTcuff). In both, lower values represent higher pain sensitivity. RESULTS: PwH exerted a worse joint health status than Con. Pain sensitivity was higher in PwH compared to Con as PPTa of the knee and ankle joints were lower in PwH. No difference was observed in PPTa at the forehead. Contrastingly, lower pain sensitivity was detected in PwH by higher PPTcuff values compared to Con in both legs. CONCLUSION: While PPTa of the knee and ankle joints are lower in PwH, PPTcuff are higher in PwH compared to Con. This reveals a paradox situation, highlighting that PwH experience local, joint- and hemophilic arthropathy-related pain, whereas pain sensitivity of non-affected soft tissue structures is lower. The reasons explaining the PPTcuff results remain elusive but might be explained by coping strategies counteracting chronic joint pain, resulting in lower sensitivity at non-affected structures.

Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram.

Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants. TMS-EEG was recorded before, during, and after noxious heat (acute pain condition) and non-noxious warm (Control condition), delivered in a randomized sequence. The main frequency bands (α, ß1, and ß2) of TMS-evoked potentials after M1 and DLPFC stimulation were recorded close to the TMS coil and remotely. Cold and heat pain thresholds were measured before TMS-EEG. Over M1, acute pain decreased α-band oscillatory power locally and α-band phase synchronization remotely in parietal-occipital clusters compared with non-noxious warm (all p < .05). The remote (parietal-occipital) decrease in α-band phase synchronization during acute pain correlated with the cold (p = .001) and heat pain thresholds (p = .023) and to local (M1) α-band oscillatory power decrease (p = .024). Over DLPFC, acute pain only decreased ß1-band power locally compared with non-noxious warm (p = .015). Thus, evoked-oscillatory cortical activity to M1 stimulation is reduced by acute pain in central and parietal-occipital regions and correlated with pain sensitivity, in contrast to DLPFC, which had only local effects. This finding expands the significance of α and ß band oscillations and may have relevance for pain therapies.

Pain tolerance as a 'barrier' to nonsuicidal self-injury: A longitudinal study.

Theoretical perspectives underscore that low pain tolerance may be a relevant 'barrier' to non-suicidal self-injury (NSSI). However, there is limited longitudinal work on the link between pain tolerance and NSSI, which is needed to assess if pain tolerance precedes NSSI engagement, and/or if NSSI precedes altered pain tolerance. Further, assessing both NSSI frequency and versatility (or number of NSSI methods), in addition to engagement, can provide a more nuanced understanding of the influence of pain on NSSI severity. In the present study, 1125 undergraduate students at a large university (72 % female, Mage = 17.96) reported on their NSSI frequency, NSSI versatility, and perceived pain tolerance. Four individual regressions were run to examine the potential bidirectional nature of the association between NSSI frequency and pain tolerance, and NSSI versatility and pain tolerance. Pain tolerance predicted both NSSI frequency and versatility over time. Neither NSSI frequency nor versatility predicted pain tolerance. Results suggest that high pain tolerance may be a risk factor for severe NSSI engagement.