Research on myofascial temporomandibular disorder (mTMD) has often focused on potential dysfunction in endogenous pain modulation. However, studies on the specific inhibitory and facilitatory components of endogenous pain modulation using conditioned pain modulation (CPM) and temporal summation of second pain (TSSP) have shown mixed results. This study aimed to 1) examine whether women with mTMD demonstrated efficient CPM compared to controls; 2) explore the association between independent measures of CPM and TSSP in women with mTMD relative to controls; and 3) determine whether resulting modulatory profiles differentially predicted pain intensity among cases. All participants were recruited from dental clinics. Cases were women who met the research diagnostic criteria for mTMD. Controls did not have facial pain on exam and were selected to be sociodemographically similar to cases. CPM and TSSP were assessed via independent psychophysical protocols. CPM was examined in linear mixed models predicting pain thresholds adjusted for age and stratified by TSSP. Mean CPM was estimated at a 2.2 (SD = 2.8) degree increase in pain thresholds (P ≤ .001), similar in cases and controls (P = .67). CPM was less efficient in cases with enhanced TSSP (P = .031), but not in controls. Although the double-pronociceptive profile of both low CPM and high TSSP trended higher among cases than controls, it did not predict higher levels of pain intensity among cases. This study does not support deficient inhibitory endogenous pain modulation in mTMD, but results suggest that inhibitory and facilitatory pain modulation should be examined concomitantly in the study of endogenous pain modulation. PERSPECTIVE: This manuscript presents a novel examination of inhibitory modulation by the level of facilitatory modulation in mTMD. The findings and approach may prove useful for mechanistic researchers studying endogenous pain modulation and clinical researchers seeking to jointly examine conditioned pain modulation and temporal summation in future research on chronic pain.

While pain after trauma generally resolves, some trauma patients experience pain for months to years after injury. An example, relevant to both combat and civilian settings, is chronic pain after traumatic brain injury (TBI). Headache as well as pain in the back and extremities are common locations for TBI-related chronic pain to be experienced. TBI-related pain can exist alone or can exacerbate pain from other injuries long after healing has occurred. Consequences of chronic pain in these settings include increased suffering, higher levels of disability, serious emotional problems, and worsened cognitive deficits. The current review will examine recent evidence regarding dysfunction of endogenous pain modulatory mechanisms, neuroplastic changes in the trigeminal circuitry and alterations in spinal nociceptive processing as contributors to TBI-related chronic pain. Key pain modulatory centers including the locus coeruleus, periaqueductal grey matter, and rostroventromedial medulla are vulnerable to TBI. Both the rationales and existing evidence for the use of monoamine reuptake inhibitors, CGRP antagonists, CXCR2 chemokine receptor antagonists, and interventional therapies will be presented. While consensus guidelines for the management of chronic post-traumatic TBI-related pain are lacking, several approaches to this clinically challenging situation deserve focused evaluation and may prove to be viable therapeutic options.

We aimed to compare the effects of three intensities of treadmill running on exercise-induced hypoalgesia (EIH) in healthy individuals. We anticipated that the primary and secondary changes in pain perception and modulation may differ between running intensities. Sixty-six women were randomly assigned to one of three treadmill running intensities for 35 min: 40% reserved heart rate (HRR), 55% HRR, or 70% HRR. The effects of EIH were assessed using pressure pain thresholds (PPT) and tolerance thresholds (PPTol). We measured conditional pain modulation (CPM). Compared with baseline, PPT and PPTol significantly increased in all groups during running and at the 5-10-min follow-up. The PPT and PPTol changes in the moderate- and low-intensity groups were significantly higher than those in the high-intensity group during running and 24 h after running, while the CPM responses of the high-intensity group were significantly reduced at the 24-h follow-up. Moderate- and low-intensity running may elicit significant primary and secondary (persisting over 24 h) EIH effects and increase CPM responses in females. However, high-intensity running induced only limited analgesic effects and reduced CPM responses, which may be attributed to the activation of endogenous pain modulation.

UNASSIGNED: Conservative pain management strategies for knee osteoarthritis (KOA) have limited effectiveness and do not employ a pain-mechanism informed approach. Pain Informed Movement is a novel intervention combining mind-body techniques with neuromuscular exercise and pain neuroscience education (PNE), aimed at improving endogenous pain modulation. While the feasibility and acceptability of this program has been previously established, it now requires further evaluation in comparison to standard KOA care.
UNASSIGNED: This protocol describes the design of a pilot two-arm randomized controlled trial (RCT) with an embedded qualitative component. The primary outcome is complete follow-up rate. With an allocation ratio of 1:1, 66 participants (33/arm) (age ≥40 years, KOA diagnosis or meeting KOA NICE criteria, and pain intensity ≥3/10), will be randomly allocated to two groups that will both receive 8 weeks of twice weekly in-person exercise sessions. Those randomized to Pain Informed Movement will receive PNE and mind-body technique instruction provided initially as videos and integrated into exercise sessions. The control arm will receive neuromuscular exercise and standard OA education. Assessment will include clinical questionnaires, physical and psychophysical tests, and blood draws at baseline and program completion. Secondary outcomes are program acceptability, burden, rate of recruitment, compliance and adherence, and adverse events. Participants will be invited to an online focus group at program completion.
UNASSIGNED: The results of this pilot RCT will serve as the basis for a larger multi-site RCT aimed at determining the program\'s effectiveness with the primary outcome of assessing the mediating effects of descending modulation on changes in pain.

UNASSIGNED: To establish the feasibility of an intervention consisting of neuromuscular exercise, mind-body techniques, and pain neuroscience education (PNE), referred to as Pain Informed Movement in people with knee Osteoarthritis (KOA). This program has the potential to improve our understanding of intrinsic pain modulation and its role in the management of chronic pain.
UNASSIGNED: This was a single-arm feasibility trial with a nested qualitative component. Primary outcome: complete follow-up. Inclusion criteria: age ≥40 years, KOA clinical diagnosis or meeting KOA NICE criteria, and pain intensity ≥3/10. The program consisted of 8-week in-person and at-home exercise sessions. PNE and mind-body techniques were provided as videos and integrated into the exercise sessions. Participants completed questionnaires and physical assessments including blood draws at baseline and program completion. Secondary feasibility outcomes: acceptability of the intervention, burden, rates of recruitment, compliance and adherence, and adverse events. A priori success criteria were identified. Participants were invited to an online focus group.
UNASSIGNED: 19 participants were enrolled, with a complete follow-up rate of 74% (mean age 63.3 years (SD 10.5), 73% female), indicating modifications were necessary to proceed. All other success criteria were met. The focus groups revealed that the video content pertaining to the mind-body techniques would benefit from on screen demonstrations.
UNASSIGNED: The Pain Informed Movement program is deemed feasible, with minor modifications needed to proceed. A pilot two-arm RCT will be conducted to establish the feasibility and explore potential effects of Pain Informed Movement compared to conventional neuromuscular exercise and standard OA education.

Digital technologies are increasingly being used to strengthen national health systems. Music is used as a management technique for pain. The objective of this study is to demonstrate the effects of a web app-based music intervention on pain. The participants were healthy adults and underwent three conditions: Conditioned Pain Modulation (CPM), Most-Liked Music (MLM) and Least-Liked Music (LLM). The music used is MUSIC CARE©, a web app-based personalized musical intervention (\"U\" Sequence based on a musical composition algorithm). Thermal pain was measured before starting the 20-min music intervention and after three time points for each music condition: 2.20, 11.30, and 20 min. Mean pain perceptions were significantly reduced under both LLM and MLM conditions. Pain decrease was more important under MLM condition than LLM condition at 2.20 min with a mean difference between both conditions of 9.7 (±3.9) (p = 0.0195) and at 11.30 min [9.2 (±3.3), p = 0.0099]. LLM is correlated with CPM but not MLM, suggesting different mechanisms between LLM and MLM. Musical intervention, a simple method of application, fits perfectly into a multidisciplinary global approach and helps to treat the pain and anxiety disorders of participants. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04862832], ClinicalTrials.gov [NCT04862832].

Relief of ongoing pain is a potent motivator of behavior, directing actions to escape from or reduce potentially harmful stimuli. Whereas endogenous modulation of pain events is well characterized, relatively little is known about the modulation of pain relief and its corresponding neurochemical basis. Here, we studied pain modulation during a probabilistic relief-seeking task (a \'wheel of fortune\' gambling task), in which people actively or passively received reduction of a tonic thermal pain stimulus. We found that relief perception was enhanced by active decisions and unpredictability, and greater in high novelty-seeking trait individuals, consistent with a model in which relief is tuned by its informational content. We then probed the roles of dopaminergic and opioidergic signaling, both of which are implicated in relief processing, by embedding the task in a double-blinded cross-over design with administration of the dopamine precursor levodopa and the opioid receptor antagonist naltrexone. We found that levodopa enhanced each of these information-specific aspects of relief modulation but no significant effects of the opioidergic manipulation. These results show that dopaminergic signaling has a key role in modulating the perception of pain relief to optimize motivation and behavior.

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.
OBJECTIVE: 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.
CONCLUSIONS: 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.

UNASSIGNED: Mechanisms underlying myofascial temporomandibular disorder (mTMD) are poorly understood. One theory is dysfunction in the central mediation of pain, specifically in enhanced facilitatory pain modulation. Because mechanisms leading to central sensitization may differ for joint and muscle pain, this study of mTMD addressed phenotypic heterogeneity by temporomandibular (TM) joint pain in the examination of quantitative sensory testing (QST).
UNASSIGNED: The stimulus dependent increase in second pain (temporal summation (TS)) and associated aftersensations (AS) were examined across groups of women with mTMD with TM joint pain and without, and a demographically matched control group.
UNASSIGNED: TS was slightly more evident in mTMD without joint pain vs with (p = 0.035), but AS were most robustly persistent in the group with joint pain vs without (p < 0.002).
UNASSIGNED: While both subgroups demonstrated evidence of central sensitization relative to controls on one of two measures, differences in QST results, if replicated, may point to possible differences in the mechanisms that yield central sensitization. Alternatively, it may represent methodological artifacts that need to be addressed. Therefore, greater consideration should be given to symptom-based phenotypes in studies examining TS and AS.

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