Exploring the association of gender role expectations of pain and measures of pain sensitization in people with knee osteoarthritis: A cross-sectional study.

OBJECTIVES: First, we explored the association between Gender Role Expectations of Pain (GREP), and psychophysical measures of sensitization in people with knee osteoarthritis (OA). Second, we explored whether the association differed by level of GREP items (high vs low scores). DESIGN: We conducted secondary analyses of a cohort study. Those who were (i) age of ≥40, English or French speaking, ii) diagnosed with knee OA using American College of Rheumatology criteria and iii) consulting with an orthopedic surgeon were included. GREP items pertaining to pain sensitivity and pain endurance of the typical man or woman were rated by males and females respectively. Psychophysical tests consisted of pressure pain thresholds (PPTs), Temporal Summation (TS), and Conditioned Pain Modulation (CPM). Multiple linear regression models for males and females were run with GREP scores (independent variables) and psychophysical tests (dependent variables). Next models stratified on the median split of GREP scores were run. Models were adjusted for age, BMI, pain catastrophizing, anxio-depressive symptoms, and radiographic severity. RESULTS: 280 participants (57% females; age (SD): 63.9 (9.6) and BMI (SD): 31.3 (8.40)) were included. GREP pain sensitivity scores in males were associated with CPM values (ß: 95% CI: 0.09 (0.01 to 0.17)). Males with low GREP pain sensitivity or pain endurance had very small to small positive associations with PPT and CPM values. CONCLUSION: This first exploration of gendered pain sensitivity and pain endurance by males and females has small and clinically unimportant associations with measures of pain sensitization requiring further validation.

Diminished vibration perception and greater pressure pain sensitivity are associated with worse knee osteoarthritis outcomes across sex and race.

OBJECTIVE: To examine associations of vibration sensitivity and pressure pain sensitivity with knee osteoarthritis (OA) outcomes across sex and race, which may relate to known sex and race disparities in clinical outcomes. DESIGN: Data were from the 2013-2015 visit of the Johnston County Osteoarthritis Project. Exposures were vibration perception threshold (VPT) measured at the bilateral medial femoral condyle (MFC) and first metatarsophalangeal joint (MTP), and pressure pain threshold (PPT) measured at the bilateral upper trapezius. Outcomes were knee pain severity and presence of knee symptoms, radiographic knee OA, and symptomatic knee OA in each knee. Cross-sectional associations of the exposures with the outcomes were examined using logistic regression models, overall and separately by sex and race. RESULTS: In the VPT and PPT analyses, 851 and 862 participants (mean age 71 years, 68% female, 33% Black, body mass index 31 kg/m2) and 1585 and 1660 knees were included, respectively. Higher VPT (lower vibration sensitivity) at the MFC and first MTP joint was associated with all outcomes. Lower PPT (greater pressure pain sensitivity) was associated with greater knee pain severity. Associations of VPT and PPT with all outcomes were similar among females and males and Black and White individuals. CONCLUSIONS: Diminished vibration perception and greater pressure pain sensitivity were cross-sectionally associated with worse knee OA outcomes. Despite differences in VPT and PPT among females and males and Black and White adults, associations with knee OA outcomes did not differ by sex or race, suggesting neurophysiological differences do not relate to established disparities.

Pain sensitivity as a state marker and predictor for adolescent non-suicidal self-injury.

BACKGROUND: The pain analgesia hypothesis suggests that reduced pain sensitivity (PS) is a specific risk factor for the engagement in non-suicidal self-injury (NSSI). Consistent with this, several studies found reduced PS in adults as well as adolescents with NSSI. Cross-sectional studies in adults with borderline personality disorder (BPD) suggest that PS may (partially) normalize after remission or reduction of BPD symptoms. The objective of the present study was to investigate the development of PS over 1 year in a sample of adolescents with NSSI and to investigate whether PS at baseline predicts longitudinal change in NSSI. METHODS: N = 66 adolescents who underwent specialized treatment for NSSI disorder participated in baseline and 1-year follow-up assessments, including heat pain stimulation for the measurement of pain threshold and tolerance. Associations between PS and NSSI as well as BPD and depressive symptoms were examined using negative binomial, logistic, and linear regression analyses. RESULTS: We found that a decrease in pain threshold over time was associated with reduced NSSI (incident rate ratio = 2.04, p = 0.047) and that higher pain tolerance at baseline predicted lower probability for NSSI (odds ratio = 0.42, p = 0.016) 1 year later. However, the latter effect did not survive Holm correction (p = 0.059). No associations between PS and BPD or depressive symptoms were observed. CONCLUSION: Our findings suggest that pain threshold might normalize with a decrease in NSSI frequency and could thus serve as a state marker for NSSI.

Chronic restraint stress induces abnormal behaviors in pain sensitivity and cognitive function in mice: the role of Keap1/Nrf2 pathway.

Stress is a series of physical and psychological responses to external and internal environmental stimuli. Growing studies have demonstrated the detrimental impacts of acute restraint stress (ARS) and chronic restraint stress (CRS) on animal behavior. However, the related pathogenesis and therapeutic mechanisms remain unclear. Hence, the present study aimed to examine whether unfolded protein response (UPR) and Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 related factor 2 (Nrf2) pathway are associated with ARS- and CRS- induced abnormal behaviors of pain sensitivity and cognitive function. We here used four behavioral tests to evaluate pain sensitivity and cognitive function in ARS and CRS mice. CRS markedly decreased Paw Withdrawal Mechanical Threshold (PWMT) and Tail-flick Latency (TFL) scores, whereas ARS altered TFL but had no effect on PWMT scores. Additionally, CRS, but not ARS, significantly changed behaviors in nest building behavior and MWMT. Intriguingly, the expression of Keap1 and Nrf2 protein were decreased in the spinal cord and hippocampus in CRS mice, but not in ARS mice. Moreover, neither the ARS nor the CRS groups significantly differed from the control group in terms of endoplasmic reticulum stress (ERS). Taken together, this study demonstrated that CRS could induce abnormal pain sensitivity and cognitive function probably via Keap1/Nrf2 pathway in spinal cord and hippocampus. It is therefore likely that effective intervention of Keap1/Nrf2 pathway may contribute to preventing and treating hyperalgesia and cognitive dysfunction in CRS.

The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model.

OBJECTIVE: Migraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA-induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene-related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP-25 through western blot analysis to gain insights into the mechanistic action of BoNT/A. METHODS: BoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post-inflammation, and alterations in CGRP release were evaluated. Changes in SNAP-25 levels were determined using western blot analysis. RESULTS: Upon CFA-induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP-25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A-treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release. CONCLUSION: Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP-25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model.

Preoperative pain sensitivity and its correlation with postoperative acute and chronic pain: a systematic review and meta-analysis.

BACKGROUND: Preoperative pain sensitivity (PPS) can be associated with postsurgical pain. However, estimates of this association are scarce. Confirming this correlation is essential to identifying patients at high risk for severe postoperative pain and for developing analgesic strategy. This systematic review and meta-analysis summarises PPS and assessed its correlation with postoperative pain. METHODS: PubMed, Scopus, Cochrane Library, and PsycINFO were searched up to October 1, 2023, for studies reporting the association between PPS and postsurgical pain. Two authors abstracted estimates of the effect of each method independently. A random-effects model was used to combine data. Subgroup analyses were performed to investigate the effect of pain types and surgical procedures on outcomes. RESULTS: A total of 70 prospective observational studies were included. A meta-analysis of 50 studies was performed. Postoperative pain was negatively associated with pressure pain threshold (PPT; r=-0.15, 95% confidence interval [CI] -0.23 to -0.07]) and electrical pain threshold (EPT; r=-0.28, 95% CI -0.42 to -0.14), but positively correlated with temporal summation of pain (TSP; r=0.21, 95% CI 0.12-0.30) and Pain Sensitivity Questionnaire (PSQ; r=0.25, 95% CI 0.13-0.37). Subgroup analysis showed that only TSP was associated with acute and chronic postoperative pain, whereas PPT, EPT, and PSQ were only associated with acute pain. A multilevel (three-level) meta-analysis showed that PSQ was not associated with postoperative pain. CONCLUSIONS: Lower PPT and EPT, and higher TSP are associated with acute postoperative pain while only TSP is associated with chronic postoperative pain. Patients with abnormal preoperative pain sensitivity should be identified by clinicians to adopt early interventions for effective analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023465727).

A brain-wide genome-wide association study of candidate quantitative trait loci associated with structural and functional phenotypes of pain sensitivity.

Individual pain sensitivity is modulated by the brain's structural and functional features, but its heritability remains unclear. This paper conducted a brain-wide genome-wide association study (GWAS) to explore the genetic bases of neuroimage phenotypes of pain sensitivity. In total, 432 normal participants were divided into high and low pain sensitivity groups according to the laser quantitative test threshold. Then, the brain's gray matter density (GMD) features correlated with pain sensitivity were identified. Next, GWAS was performed on each GMD phenotype using quality-controlled genotypes. Based on the heatmap and hierarchical clustering results, the right insula was identified for further refined analysis in terms of subregions GMD and resting-state functional connectivity (rs-FC) phenotypes. The results indicate that the right insula GMD in the high sensitivity group is significantly lower than that in the low sensitivity group. Also, the TT/TC group at locus rs187974 has lower right insula GMD than the CC group. Further, loci at gene CYP2D6 may lead to a variation of rs-FC between the right insula and left putamen. In conclusion, our study suggests that the right insula and multiple candidate loci may be importantly involved in pain sensitivity modulation, which may guide the future development of precision pain therapeutics.

Individuals with fibromyalgia report greater pain sensitivity than healthy adults while listening to their favorite music: the contribution of negative affect.

OBJECTIVE: We investigated the impact of favorite music on pain processing among individuals with fibromyalgia. We also examined differences in pain processing between individuals with fibromyalgia and healthy controls (HC) while listening to favorite music and explored whether psychosocial factors contributed to these differences. METHODS: Individuals with fibromyalgia and HC completed baseline psychosocial questionnaires and then underwent quantitative sensory testing (QST) during 3 randomized music conditions (meditative music, favorite music, white noise). Among individuals with fibromyalgia, Friedman tests were used to investigate differences in QST across conditions. Analyses of Covariance were used to examine group (HC vs fibromyalgia) differences in QST during favorite music. Correlations were conducted to explore associations of baseline psychosocial factors with QST during favorite music. Mediation analyses were conducted to explore whether psychosocial factors contributed to greater pain sensitivity among individuals with fibromyalgia compared to HC during favorite music. RESULTS: Individuals with fibromyalgia were less sensitive to pressure pain while listening to their favorite music compared to white noise. Compared to HC, individuals with fibromyalgia reported higher baseline negative affect and lower pain thresholds and tolerances during favorite music. Negative affect partially mediated the relationship between pain status (HC vs fibromyalgia) and pain sensitivity during favorite music. CONCLUSIONS: Individuals with fibromyalgia were less pain sensitive while listening to favorite music than white noise, although they were more sensitive than HC. Greater negative affect endorsed by individuals with fibromyalgia contributed to their greater pain sensitivity. Future studies should explore the impact of favorite music on clinical pain. CLINICAL TRAILS REGISTRATION: This study was registered with ClinicalTrials.gov (NCT04087564) and began on 6/13/2019.

Blood flow restriction augments exercise-induced pressure pain thresholds over repetition and effort matched conditions.

We sought to determine the effects of blood flow restriction (BFR) on exercise-induced hypoalgesia, specifically using low-load (LL) resistance exercise (30% 1RM) protocols that accounted for each individual's local muscular endurance capabilities. Forty-four participants completed four conditions: (1) 70% of maximal BFR repetitions with blood flow restriction (LL+BFR exercise); (2) 70% maximal BFR repetitions without LL+BFR (LL exercise); (3) 70% maximal free flow repetitions (LL+EFFORT exercise); (4) time-matched, non-exercise control (CON). Pressure pain threshold (PPT) was measured before and after exercise. Ischaemic pain threshold and tolerance was assessed only at post. The change in upper body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.15 (0.35) kg/cm2], LL+EFFORT exercise [difference of 0.23 (0.45) kg/cm2], and the CON condition. The change in lower body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.40 (0.55) kg/cm2], LL+EFFORT exercise [difference of 0.36 (0.62) kg/cm2], and the CON condition. Ischaemic pain thresholds and tolerances did not change. Submaximal exercise with BFR resulted in systemic increases in PPT but had no influence on ischaemic pain sensitivity. This effect is likely unique to BFR as we did not see changes in the effort matched free flow condition.

Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and positively influences pain sensitivity and work capacity.

The aim of the study was to investigate the effects of rat housing conditions-standard conditions, social isolation, environmental enrichment-and the subsequent reversal of these conditions on the vulnerability of the gastric mucosa to ulcerogenic stimuli, somatic pain sensitivity, and treadmill work capacity. Rats, aged 30 days, were placed in standard conditions (SC), social isolation (Is), and environmental enrichment (EE) for 4 weeks. Then half of each group underwent a reversal of housing conditions: SC rats were moved to Is, Is rats were placed in EE, EE rats were moved to Is, for 2 weeks. The other half served as a control with no change in their initial housing. Two weeks after the reversal, vulnerability of the gastric mucosa to ulcerogenic action of indomethacin (IM, 35 mg/kg, sc), somatic pain sensitivity (hot plate test), and work capacity (measured by the running distance on a treadmill) were assessed in control and reversed groups. Social isolation induced a proulcerogenic effect, increasing IM-induced gastric erosions, which was effectively reversed when rats were transferred to an environmental enrichment. Conversely, transferring rats from an environmental enrichment to social isolation exacerbated ulcerogenic action of IM. Somatic pain sensitivity and treadmill work capacity were also influenced by housing conditions, with environmental enrichment showing positive effects. The present findings show that social isolation of rats induces a proulcerogenic effect. Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and increases resilience to pain stimuli and treadmill work capacity.

Activation of vascular endothelial cells by synovial fibrosis promotes Netrin-1-induced sensory nerve sprouting and exacerbates pain sensitivity.

Synovial fibrosis is one of the most dominant histopathological changes in osteoarthritis of the knee (KOA), and activation of vascular endothelial cells in synovial fibrosis is both an important factor in mediating pain in KOA and a major contributor to the generation of pain signals. At the same time, angiogenesis and nerve fibres are more likely to underlie the pathology of pain induced by synovial fibrosis. In the present study, we established a co-culture model of human umbilical vein endothelial cells (HUVECs) with dorsal root ganglion (DRG) and detected tissue and cellular Netrin-1, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), growth-associated protein-43 (GAP43), colorectal cancer deleted (DCC), uncoordinated 5 (UNC5), and the related expression of calcitonin gene-related peptide (CGRP), substance P (SP) and nerve growth factor (NGF) in supernatant by ELISA to investigate the intervention of vascular endothelial cell activation on sensory nerve sprouting exacerbating peripheral pain sensitivity and to investigate the effect of Netrin-1 from the perspective of Netrin-1 secretion to illustrate its effector mechanism.

Relationship between individual differences in pain empathy and task- and resting-state EEG.

Pain empathy is a complex form of psychological inference that enables us to understand how others feel in the context of pain. Since pain empathy may be grounded in our own pain experiences, it exhibits huge inter-individual variability. However, the neural mechanisms behind the individual differences in pain empathy and its association with pain perception are still poorly understood. In this study, we aimed to characterize brain mechanisms associated with individual differences in pain empathy in adult participants (n = 24). The 32-channel electroencephalography (EEG) was recorded at rest and during a pain empathy task, and participants viewed static visual stimuli of the limbs submitted to painful and nonpainful stimulation to solicit empathy. The pain sensitivity of each participant was measured using a series of direct current stimulations. In our results, the N2 of Fz and the LPP of P3 and P4 were affected by painful pictures. We found that both delta and alpha bands in the frontal and parietal cortex were involved in the regulation of pain empathy. For the delta band, a close relationship was found between average power, either in the resting or task state, and individual differences in pain empathy. It suggested that the spectral power in Fz's delta band may reflect subjective pain empathy across individuals. For the alpha band, the functional connectivity between Fz and P3 under painful picture stimulation was correlated to individuals' pain sensitivity. It indicated that the alpha band may reflect individual differences in pain sensitivity and be involved in pain empathy processing. Our results suggested the distinct role of the delta and alpha bands of EEG signals in pain empathy processing and may deepen our understanding of the neural mechanisms underpinning pain empathy.

Psychophysical assessment of pain in adults with moderate and severe haemophilia: A cross-sectional study.

BACKGROUND: Joint pain is the hallmark of haemophilia; therefore it seems clinically rather a musculoskeletal than a bleeding disorder. Although joint pain in people with haemophilia (PwH) is a complex and multidimensional problem, pain assessment remains primarily focused on the structural evaluation of their joints. Whereas, only few data are available on the potential implication of psychophysical and psychological factors. OBJECTIVE: This study aimed to perform a psychophysical pain assessment including quantitative sensory testing (QST) and an evaluation of psychological factors in a large sample of PwH, to get insight into the individuals' pain system. METHODS: Ninety-nine adults (36.9 ± 13.5 years) with moderate/severe haemophilia A/B and 46 healthy controls filled in self-reported pain and psychological questionnaires and underwent a QST evaluation including static and dynamic tests. Static tests focused on the determination of thermal detection and pain thresholds and mechanical pressure pain thresholds. Dynamic tests evaluated pain facilitation and the efficacy of endogenous pain inhibition. Besides comparing PwH and healthy controls, between-subgroup differences were studied in PwH based on their pain distribution. RESULTS: The study revealed increased thermal and mechanical pain sensitivity and the presence of unhelpful psychological factors such as anxiety/depression in PwH. Among the subgroups, especially PwH with widespread pain showed altered somatosensory functioning. Enhanced pain facilitation and impaired efficacy of endogenous pain inhibition in PwH could not be observed. CONCLUSION: Altered somatosensory functioning and unhelpful psychological factors, appear to play an important role in the pathophysiology of pain in PwH, especially in PwH with widespread pain.

Profiling migraine patients according to clinical and psychophysical characteristics: a cluster analysis approach.

AIM: This study aims to profile migraine patients according clinical and psychophysical characteristics. METHOD: In this observational study, two cohorts of migraine patients(episodic/chronic) were included. Cohort-1: ictal/perictal phase; Cohort-2: interictal phase.The following variables were assessed: headache frequency; disability; cervical active range of motion(AROM) in flexion, extension, right/left lateral flexion, right/left rotation; pressure-pain threshold(PPT) over: temporalis, two cervical areas(C1/C4 vertebral segments), and two distal pain-free areas(hand/leg). Cluster analysis was performed using the K-means algorithm. Differences across clusters were investigated. RESULTS: Cohort-1: 100 patients were included, and two clusters were identified. Cluster-1.1 (19%), Cluster-1.2 (81%). Cluster 1.1 had a higher percentage of men (P = .037) and higher disability (P = .003) compared to Clusters 1.2. Cluster 1.2 had reduced AROM in flexion, extension, and left/right lateral flexion (P < .037), and lower PPT value in all areas (P < .001) compared to Cluster 1.1. Cohort-2: 98 patients were included and three clusters were identified. Cluster-2.1(18%), Cluster-2.2(45%), and Cluster-2.3(37%). Cluster-2.1 had a higher percentage of men compared to clusters-2.2 and 2.3 (P = .009). Cluster-2.3 had higher headache frequency, and disability compared to Cluster-2.2 (P < .006), and higher disability compared to Cluster-2.1 (P = .010). Cluster-2.3 had reduced AROM in all directions compared to Clusters-2.1 and 2.2 (P < .029). Clusters-2.2 and 2.3 have lower PPT values in all areas compared to Cluster-1.1 (P < .001). CONCLUSION: In the Ictal/perictal phase, two clusters were identified according to clinical and psychophysical characteristics, with one group showing no psychophysical impairment and one with increased pain-sensitivity and cervical musculoskeletal-dysfunctions.In the interictal phase, three clusters could be identified, with one group showing no psychophysical impairment, one increased pain-sensitivity, and one increased pain sensitivity and cervical musculoskeletal-dysfunctions.

Trigeminocervical pain sensitivity during the migraine cycle depends on headache frequency.

OBJECTIVE: This experimental study aimed to assess pain sensitivity in low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM), and chronic migraine (CM) patients across the different phases of the migraine cycle. METHOD: In this observational, experimental study, clinical characteristics (diary and time from the last/next headache attack), and quantitative sensory testing (QST) (wind-up pain ratio (WUR) and pressure pain threshold (PPT) from the trigeminal area and PPT from the cervical spine) was performed. LFEM, HFEM, and CM were assessed in each of the 4 migraine phases (HFEM and LFEM: interictal, preictal, ictal, and postictal; CM: interictal and ictal) and compared vs. each other's (matched for the phase) and controls. RESULTS: A total of 56 controls, 105 LFEM, 74 HFEM, and 32 CM were included. No differences in QST parameters were observed between LFEM, HFEM, and CM in any of the phases. During the interictal phase and when comparing with controls the following were found: 1) LFEM had lower trigeminal PPT (p = 0.001) and 2) lower cervical PPT (p = 0.001). No differences were observed between HFEM or CM and healthy controls. During the ictal phase and when comparing with controls the following were found: HFEM and CM had 1) lower trigeminal PPTs (HFEM p = 0.001; CM = p < 0.001), 2) lower cervical PPT s (HFEM p = 0.007; CM p < 0.001), and 3) higher trigeminal WUR (HFEM p = 0.001, CM p = 0.006). No differences were observed between LFEM and healthy controls. During the preictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.007), 2) HFEM had lower trigeminal (p = 0.013) and 3) HFEM had lower cervical (p = .006) PPTs. During the postictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.003), 2) HFEM had lower trigeminal PPT (p = 0.005), and 3) and HFEM had lower cervical (p = 0.007) PPTs. CONCLUSION: This study suggested that HFEM patients have a sensory profile matching CM better than LFEM. When assessing pain sensitivity in migraine populations, the phase with respects to headache attacks is of utmost importance and can explain the inconsistency in pain sensitivity data reported in the literature.

Developing non-opioid therapeutics to alleviate pain among persons with opioid use disorder: a review of the human evidence.

The opioid crisis remains a major public health concern, causing significant morbidity and mortality worldwide. Pain is frequently observed among individuals with opioid use disorder (OUD), and the current opioid agonist therapies (OAT) have limited efficacy in addressing the pain needs of this population. We reviewed the most promising non-opioid analgesic therapies for opioid-dependent individuals synthesising data from randomised controlled trials in the Medline database from December 2022 to March 2023. Ketamine, gabapentin, serotoninergic antidepressants, and GABAergic drugs were found to be the most extensively studied non-opioid analgesics with positive results. Additionally, we explored the potential of cannabinoids, glial activation inhibitors, psychedelics, cholecystokinin antagonists, alpha-2 adrenergic agonists, and cholinergic drugs. Methodological improvements are required to advance the development of novel analgesic strategies and establish their safety profile for opioid-dependent populations. We highlight the need for greater integration of experimental pain methods and abuse liability assessments, more granular assessments of prior opioid exposure, greater uniformity of pain types within study samples, and a particular focus on individuals with OUD receiving OAT. Finally, future research should investigate pharmacokinetic interactions between OAT and various non-opioid analgesics and perform reverse translation basic experiments, particularly with methadone and buprenorphine, which remain the standard OUD treatment.

Is your pain my pain? A study exploring the relation between pain sensitivity, pain thresholds and empathy for somatic and psychological pain.

OBJECTIVES: Research has shown that empathy for both somatic and psychological pain recruits affective components of the so-called pain matrix, a set of brain regions that is activated during the perception of somatic pain. In addition, the subjective evaluation of experimentally induced somatic pain is related to empathy for somatic pain. In contrast, it is unclear whether or not the subjective sensitivity to somatic pain impacts on empathy for psychological pain. METHODS: In the present study, 55 healthy participants conducted a pain-pressure-test (PPT) and a cold-pressor test (CPT) in order to assess pain thresholds, pain tolerance and evaluation of pain during the task. They further conducted the social interaction empathy task (SIET), which investigates empathy for somatic as well as psychological pain. All participants completed the interpersonal-reactivity index (IRI) and the pain-sensitivity questionnaire (PSQ). RESULTS: Participants who are in general more sensitive to somatic pain, as indicated by high-PSQ scores, showed higher empathy, that is, higher pain ratings, for both somatic and psychological painful situations observed in others as compared to those with low-PSQ scores. High-PSQ scores and high pain and unpleasantness ratings during the CPT were correlated with empathy for pain (both pain conditions), whereas pain thresholds (PPT) and pain tolerance thresholds (CPT) did not correlate with empathy. The IRI subscore 'personal distress' correlated with psychological pain ratings. CONCLUSIONS: Thus, empathy for both somatic and psychological pain were related to the subjective evaluation of somatic pain and general pain sensitivity.

Skin temperature normalizes faster than pressure pain thresholds, pain intensity, and pain distribution during recovery from eccentric exercise.

INTRODUCTION: Acute musculoskeletal injuries have diverse symptomatology and a multidimensional recovery process, including changes in swelling, redness, hyperalgesia, and expanded pain distribution. In a small proportion of cases, the tissue heals, although these symptoms persist, reflecting altered peripheral and central pain mechanisms. However, the otherwise healthy multidimensional recovery process following damage and pain is less than clear. The objective was to assess mechanical muscle hyperalgesia, skin temperature, and pain intensity and distribution during the recovery process in response to eccentric exercise in the hamstring muscles. METHODS: Twenty-four healthy males participated in four sessions (Day-0, Day-2, Day-4, and Day-7). Exercise-induced muscle soreness was induced on Day-0 by five sets of 20 repetitions of an eccentric exercise involving the hamstrings on the dominant leg. Each session included assessments of thermography, pressure pain thresholds (PPTs), pain intensity, and area of exercise-induced pain. RESULTS: Decreased PPTs (P < 0.005), higher pain intensity (P < 0.001), and a larger area of pain (P < 0.001) were displayed on Day-2 and Day-4 than Day-0. Skin temperature decreased on Day-2 than Day-0 (P < 0.01) and returned to baseline assessments by Day-4, despite lower temperature than the contralateral tight (P < 0.01). Further, there was a positive correlation between pain intensity and area on Day-2 and Day-4 (P < 0.005), but no for changes in skin temperature. CONCLUSION: Thermographic changes and pain-related variables altered following eccentric exercise demonstrate different recovery times. These results provide insights into potential mechanisms and measures that can be used to assess recovery from exercise-induced damage.

Influence of genetic polymorphisms on mechanical pain sensitivity and endogenous pain modulation of trigeminal and spinal areas.

BACKGROUND: Previous evidence indicates significant association between genetic polymorphisms and phenotypes related to pain sensitivity in patients with temporomandibular disorders (TMD). Despite the important advances in cataloguing diverse factors such as sleep disorders, anxiety and depression, the interrelated mechanisms of painful TMD aetiopathogenesis still need investigation. OBJECTIVES: This case-control study aimed to evaluate the influence of genetic polymorphisms (rs6296, rs6295, rs1799971, rs4680, rs4633, rs4818) and psychosocial factors on the mechanical pain sensitivity and endogenous pain modulation in women with painful TMD and asymptomatic controls. METHODS: We evaluated six independent variables: anxiety levels, depression, stress, sleep quality, pain catastrophising and genetic polymorphisms, and four dependent variables: mechanical pain threshold (MPT), pressure pain threshold (PPT), wind-up ratio (WUR) and conditioned pain modulation (CPM) collected at masseter (trigeminal) and hand (spinal) areas in a sample of 95 painful TMD patients and 85 controls. A regression model was used to test the possible effect of the independent variables on dependent variables. RESULTS: The regression model was significant for MPT (F11,168  = 9.772; R2  = .390). Painful TMD diagnoses and sleep quality were associated with trigeminal MPT (B coefficient = -.499; and B coefficient = -.211, respectively). WUR was associated with rs6295 and rs6746030, respectively, for the spinal and the trigeminal area. CONCLUSION: Genetic polymorphisms had a slight contribution to endogenous pain modulation as indicated by the significant association with WUR but did not contribute to mechanical pain sensitivity. On the other hand, the presence of painful TMD and the sleep quality contributed significantly to mechanical pain sensitivity.

Pain sensitivity and quality of life of patients with burning mouth syndrome: a preliminary study in a Chinese population.

BACKGROUND: Burning mouth syndrome (BMS) is an oral-facial pain disorder involving the central and peripheral nervous systems, but the evidence for altered pain sensitivity remains inconclusive. The aim of this study was to investigate pain sensitivity and oral health-related quality of life (OHRQoL) in patients with BMS and to assess the relationship between them. METHODS: Fifty Chinese patients with BMS (57.82 ± 11.2 years) and fifty age- and gender-matched healthy subjects (55.64 ± 10.1 years) participated in the study. The Pain Sensitivity Questionnaire (PSQ) was used to assess participants' pain sensitivity. The Oral Health Impact Profile (OHIP-14) was used to evaluate participants' OHRQoL. RESULTS: The PSQ total score (p = 0.009), the PSQ minor score (p = 0.003) and the OHIP-14 score (p<0.05) of patients with BMS were significantly higher than those of the healthy subjects. Simple linear regression showed that the PSQ minor score was significantly associated with the OHIP-14 score in patients with BMS (ß = 0.338, p = 0.016). CONCLUSION: Patients with BMS have higher pain sensitivity than healthy subjects. Reducing pain sensitivity might help to improve the quality of life of patients with BMS.