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.

Descending pain modulatory efficiency in healthy subjects is related to structure and resting connectivity of brain regions.

The descending pain modulatory system in humans is commonly investigated using conditioned pain modulation (CPM). Whilst variability in CPM efficiency, i.e., inhibition and facilitation, is normal in healthy subjects, exploring the inter-relationship between brain structure, resting-state functional connectivity (rsFC) and CPM readouts will provide greater insight into the underlying CPM efficiency seen in healthy individuals. Thus, this study combined CPM testing, voxel-based morphometry (VBM) and rsFC to identify the neural correlates of CPM in a cohort of healthy subjects (n =40), displaying pain inhibition (n = 29), facilitation (n = 10) and no CPM effect (n = 1). Clusters identified in the VBM analysis were implemented in the rsFC analysis alongside key constituents of the endogenous pain modulatory system. Greater pain inhibition was related to higher volume of left frontal cortices and stronger rsFC between the motor cortex and periaqueductal grey. Conversely, weaker pain inhibition was related to higher volume of the right frontal cortex - coupled with stronger rsFC to the primary somatosensory cortex, and rsFC between the amygdala and posterior insula. Overall, healthy subjects showed higher volume and stronger rsFC of brain regions involved with descending modulation, while the lateral and medial pain systems were related to greater pain inhibition and facilitation during CPM, respectively. These findings reveal structural alignments and functional interactions between supraspinal areas involved in CPM efficiency. Ultimately understanding these underlying variations and how they may become affected in chronic pain conditions, will advance a more targeted subgrouping in pain patients for future cross-sectional studies investigating endogenous pain modulation.

Somatosensory dysfunction in patients with posttraumatic headache: A systematic review.

OBJECTIVES: Aim of the review is to summarize the knowledge about the sensory function and pain modulatory systems in posttraumatic headache and discuss its possible role in patients with posttraumatic headache. BACKGROUND: Posttraumatic headache is the most common complication after traumatic brain injury, and significantly impacts patients' quality of life. Even though it has a high prevalence, its origin and pathophysiology are poorly understood. Thereby, the existing treatment options are insufficient. Identifying its mechanisms can be an important step forward to develop target-based personalized treatment. METHODS: We searched the PubMed database for studies examining pain modulation and/or quantitative sensory testing in individuals with headache after brain injury. RESULTS: The studies showed heterogenous alterations in sensory profiles (especially in heat and pressure pain perception) compared to healthy controls and headache-free traumatic brain injury-patients. Furthermore, pain inhibition capacity was found to be diminished in subjects with posttraumatic headache. CONCLUSIONS: Due to the small number of heterogenous studies a distinct sensory pattern for patients with posttraumatic headache could not be identified. Further research is needed to clarify the underlying mechanisms and biomarkers for prediction of development and persistence of posttraumatic headache.

Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45, 47, and 48.9°C) in 38 healthy men (age: 27.05 ± 5.7 years). We also reconstructed the MFB using multitensor tractography from diffusion magnetic resonance imaging (dMRI) and calculated free-water corrected dMRI measures of fractional anisotropy (FAt ), radial diffusivity (RDt ), and axial diffusivity (ADt ). Lower ratings of interindividual pain intensity correlated with higher FAt and lower RDt of the MFB. As changes in FAt and RDt may reflect abnormalities in myelination, the results might be interpreted as that a lower pain rating is associated with higher degree of myelination of the MFB and could represent an inhibitory pathway of pain. Our results suggest that alteration of microstructure in the MFB contributes to the interindividual variation of pain perception.

Recovery of Impaired Endogenous Pain Modulation by Dopaminergic Medication in Parkinson's Disease.

BACKGROUND: Of patients with Parkinson's disease (PD), 30% to 85% report pain. However, mechanisms underlying this pain remain unclear. In line with known neuroanatomical impairments, we hypothesized that pain in PD is caused by alterations in emotional-motivational as opposed to sensory-discriminative pain processing and that dopamine recovers the capacity for endogenous emotional-motivational pain modulation in patients with PD. METHODS: A total of 20 patients with PD played a random reward paradigm with painful heat stimuli in addition to assessments of pain sensitivity once with and once without levodopa. RESULTS: Levodopa increased endogenous pain inhibition in terms of perceived pain intensity and un/pleasantness compared with a medication off state. Higher clinical pain was associated with higher increases in pain inhibition. Levodopa did not affect heat pain threshold, tolerance, or temporal summation. CONCLUSION: Patients with PD seem to be predominately impaired in emotional-motivational as opposed to sensory-discriminative pain processing. A differential understanding of pain in PD is urgently needed because effective treatment strategies are lacking. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature.

OBJECTIVE: Descending pain modulation can be experimentally assessed by way of testing conditioned pain modulation. The application of tonic heat as a test stimulus in such paradigms offers the possibility of observing dynamic pain responses, such as adaptation and temporal summation of pain. Here we investigated conditioned pain modulation effects on tonic heat employing participant-controlled temperature, an alternative tonic heat pain assessment. Changes in pain perception are thereby represented by temperature adjustments performed by the participant, uncoupling this approach from direct pain ratings. Participant-controlled temperature has emerged as a reliable and sex-independent measure of tonic heat. METHODS: Thirty healthy subjects underwent a sequential conditioned pain modulation paradigm, in which a cold water bath was applied as the conditioning stimulus and tonic heat as a test stimulus. Subjects were instructed to change the temperature of the thermode in response to variations in perception to tonic heat in order to maintain their initial rating over a two-minute period. Two additional test stimuli (i.e., lower limb noxious withdrawal reflex and pressure pain threshold) were included as positive controls for conditioned pain modulation effects. RESULTS: Participant-controlled temperature revealed conditioned pain modulation effects on temporal summation of pain (P = 0.01). Increased noxious withdrawal reflex thresholds (P = 0.004) and pressure pain thresholds (P < 0.001) in response to conditioning also confirmed inhibitory conditioned pain modulation effects. CONCLUSIONS: The measured interaction between conditioned pain modulation and temporal summation of pain supports the participant-controlled temperature approach as a promising method to explore dynamic inhibitory and facilitatory pain processes previously undetected by rating-based approaches.

Enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.

Chronic pain in persons living with HIV (PLWH) may be related to alterations in endogenous pain modulatory processes (e.g., high facilitation and low inhibition of nociception) that promote exaggerated pain responses, known as hyperalgesia, and central nervous system (CNS) sensitization. This observational study examined differences in endogenous pain modulatory processes between 59 PLWH with chronic pain, 51 PLWH without chronic pain, and 50 controls without HIV or chronic pain. Quantitative sensory testing for temporal summation (TS) of mechanical and heat pain as well as conditioned pain modulation (CPM) were used to assess endogenous pain facilitatory and inhibitory processes, respectively. Associations among TS, CPM, and self-reported clinical pain severity were also examined in PLWH with chronic pain. Findings demonstrated significantly greater TS of mechanical and heat pain for PLWH with chronic pain compared to PLWH without chronic pain and controls. CPM effects were present in controls, but not in either PLWH with or without chronic pain. Among PLWH with chronic pain, greater TS of mechanical pain was significantly associated with greater average clinical pain severity. Results of this study suggest that enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.

Endogenous pain modulation assessed with offset analgesia is not impaired in chronic temporomandibular disorder pain patients.

BACKGROUND: Abnormal endogenous pain modulation (EPM) was suggested as a pathophysiological characteristic of chronic pain. EPM has been investigated using psychophysical tests for pain facilitation and inhibition such as temporal summation of pain and conditioned pain modulation, respectively. Another psychophysical test for pain inhibition is offset analgesia (OA), where small variations in noxious stimulus intensity over time elicit a disproportionately large analgesic response. OA has been investigated in patients with mixed pain conditions, but not in chronic temporomandibular disorder (TMD) patients. OBJECTIVE: To compare OA responses in chronic TMD female cases to age-matched, pain-free female controls. METHODS: Offset analgesia was assessed by applying noxious heat over the non-dominant forearm of chronic TMD cases (n = 22) and controls (n = 17), using a previously reported paradigm with individualised test temperatures (TT): T1(5 seconds) = TT, T2(5 seconds) = TT + 1°C and T3(20 seconds) = TT. Clinical and psychosocial characteristics were measured. Main outcomes for OA were delta computerised visual analogue scale (COVAS), per cent change (T2-T3/T2-T1) and area under the curve (AUC) ratio of pain ratings controlling for TT. RESULTS: No statistically significant between-group differences were found for delta COVAS (TMD cases mean ± SD = 53.5 ± 22.0; controls = 51.6 ± 22.9, P = 0.876) and per cent change (T2-T3/T2-T1) (cases mean = 327.2 ± 375.1; controls = 226.9 ± 553.4, P = 0.515), with both groups presenting a robust OA response. TMD cases perceived more pain during OA trials than controls, as measured by AUC ratio (mean difference [95% CI] = -15.6 [-26.9, -3.5], P = 0.017). CONCLUSION: Chronic TMD cases presented with similar OA response over the forearm as controls; however, they experienced greater pain during testing. Future studies including this patient population should investigate OA responses over painful body sites, for example, jaw/face.

Endogenous pain modulation in chronic temporomandibular disorders: Derivation of pain modulation profiles and assessment of its relationship with clinical characteristics.

BACKGROUND: Endogenous pain modulation (EPM) reflects the brain's ability to modulate incoming nociceptive inputs, and deficient EPM was implicated as a chronic pain mechanism. EPM status has been investigated in temporomandibular disorders (TMD) patients with conflicting results, and its relationship with clinical characteristics in this population is not well known. OBJECTIVES: (a) Determine EPM responses in chronic TMD cases and pain-free controls; (b) Derive pain modulation profiles (PMP) based on individual EPM responses; and (c) Categorise clinical characteristics of TMD cases and pain-free controls based on their individual PMP. METHODS: Twenty-two chronic TMD cases and 17 age-matched pain-free controls, all females, were comprehensively characterised regarding clinical characteristics and underwent EPM testing using temporal summation of pain (TSP) and conditioned pain modulation (CPM) protocols over the face and hand. Individuals were categorised into PMPs (I-IV) based on predetermined cut-off points for TSP and CPM responses. RESULTS: Between-group comparisons showed similar TSP and CPM responses (P > 0.23) in the face, while TMD cases showed significantly increased TSP (P = 0.04) but similar CPM responses (P > 0.17) in the hand relative to controls. Similar distribution across PMPs and clinical characteristics when categorised into PMPs was found for both groups. Body mass index was associated with increased TSP and reduced CPM in the face in TMD cases. CONCLUSION: Endogenous pain modulation responses over the face were similar between groups. TMD cases showed increased hand TSP compared to controls while both groups showed no significant hand CPM. PMP classification showed similar results between groups, and further refinement of PMP determination is warranted.

Noxious mechanical heterotopic stimulation induces inhibition of the spinal dorsal horn neuronal network: analysis of spinal somatosensory-evoked potentials.

Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.

Mechanisms and treatments of chronic pain after traumatic brain injury.

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.

Feasibility of pain informed movement program for people with knee osteoarthritis.

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Pain Informed Movement for people with knee osteoarthritis: Protocol for a pilot randomized controlled trial.

Objective: 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. Design: 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. Conclusion: 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.

Modulation of pain perceptions following treadmill running with different intensities in females.

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.

Examination of Conditioned Pain Modulation in Myofascial TMD With Consideration of Temporal Summation.

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.

Evidence for dopaminergic involvement in endogenous modulation of pain relief.

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.

A web app-based music intervention reduces experimental thermal pain: A randomized trial on preferred versus least-liked music style.

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].

Temporal Summation and Aftersensations of Second Pain in Women with Myofascial Temporomandibular Disorder Differ by Presence of Temporomandibular Joint Pain.

Purpose: 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). Patients and Methods: 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. Results: 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). Conclusion: 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.

Family History of Alcohol Use Disorder as a Predictor of Endogenous Pain Modulation Among Moderate to Heavy Drinkers.

Family history of alcohol use disorder (AUD) is frequently endorsed by persons with chronic pain. Although individuals with a family history of AUD have demonstrated enhanced sensitivity to painful stimulation, previous research has not examined endogenous pain modulation in this population. The goal of this study was to test family history of AUD as a predictor of conditioned pain modulation, offset analgesia, and temporal summation among a sample of moderate and heavy drinkers. Adults with no current pain (N = 235; 58.3% male; Mage = 34.3; 91.9% non-Hispanic; 60% white) were evaluated for family history of AUD at baseline and pain modulatory outcomes were assessed via quantitative sensory testing. Participants with a family history of AUD (relative to those without) evinced a pro-nociceptive pain modulation profile in response to experimental pain. Specifically, family history of AUD was associated with deficits in pain-inhibitory processes. Approximately 4% of the variance in endogenous pain modulation was accounted for by family history, and exploratory analyses suggested these effects may be driven by paternal AUD. PERSPECTIVE: The current findings suggest individuals with a family history of AUD demonstrate pain modulatory function that may predispose them to the development of chronic pain. Clinically, these data may inform pain management approaches for individuals with a family history of AUD.

Pain and executive function: no association between remote exercise-induced hypoalgesia and cognitive inhibition in pain-free participants.

OBJECTIVES: Cognitive inhibition, which denotes the ability to suppress predominant or automatic responses, has been associated with lower pain sensitivity and larger conditioned pain modulation in humans. Studies exploring the association between cognitive inhibition and other pain inhibitory phenomena, like exercise-induced hypoalgesia (EIH), are scarce. The primary aim was to explore the association between cognitive inhibition and EIH at exercising (local) and non-exercising (remote) muscles after isometric exercise. The secondary aim was to explore the association between cognitive inhibition and pressure pain sensitivity. METHODS: Sixty-six pain-free participants (28.3 ± 8.9 years old, 34 women) completed two cognitive inhibition tasks (stop-signal task and Stroop Colour-Word task), a 3-min isometric wall squat exercise, and a quiet rest control condition with pre- and post-assessments of manual pressure pain thresholds at a local (thigh) and a remote site (shoulder). In addition, cuff pressure pain thresholds, pain tolerance and temporal summation of pain were assessed at baseline. RESULTS: No association was found between remote EIH and cognitive inhibition (Stroop interference score: r=0.12, [-0.15; 0.37], p=0.405, BF01=6.70; stop-signal reaction time: r=-0.08, [-0.32; 0.17], p=0.524, BF01=8.32). Unexpectedly, individuals with worse performance on the Stroop task, as indicated by a higher Stroop interference score, showed higher local EIH (r=0.33; [0.10; 0.53], p=0.007, BF01=0.29). No associations were observed between pain sensitivity and any of the cognitive inhibition performance parameters. CONCLUSIONS: The present findings do not support previous evidence on positive associations between exercise-induced hypoalgesia and cognitive inhibition, as well as baseline pain sensitivity and cognitive inhibition.