Muscle oxygenation and pain in different types of temporomandibular disorders.

OBJECTIVES: Studies exploring variations in peripheral muscle oxygenation and pressure pain thresholds (PPT) of masticatory muscles in individuals with Temporomandibular Disorders (TMDs) are limited. The purpose of this study was to compare variations in peripheral oxygenation of the masseter muscle; PPT of the masseter and temporal muscles and correlate peripheral muscle oxygenation and PPT of the masseter muscle in individuals with different types of TMDs. MATERIALS AND METHODS: Cross-sectional study involving 116 participants classified into three groups: muscle group (MG, n = 32), joint group (JG, n = 30) and muscle-joint group (MJG, n = 54). Individuals aged 26.97 ± 6.93, 68.97% female, 31,03% males were included. All participants were evaluated using the Diagnostic Criteria for Temporomandibular Disorders, Near-infrared spectroscopy (NIRS) for peripheral muscle oxygenation and pressure algometer for PPT. RESULTS: There was no difference in masseter muscle oxygenation among groups. In the masseter muscle, a weakly positive correlation was observed between PPT and variation in tissue saturation index in the MG (rho = 0.365) and JG (rho = 0.317). In addition, the MJG expressed lower PPT (p = 0.004) than JG, demonstrating that MJG had more pain in this muscle. CONCLUSIONS: MJG have lower PPT in the masseter muscle. Although the PPT is dependent on the type of TMDs, the correlation between PPT and oxygenation is weak. All TMDs groups evaluated (MG, JG, MJG) showed hemodynamic similarities of the masseter muscle. CLINICAL RELEVANCE: Understanding pain thresholds and the hemodynamic behavior of the masticatory muscles contributes to a more assertive physiotherapeutic assessment in TMDs, serving as a basis for careful and individualized interventions.

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

BACKGROUND: Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. OBJECTIVES: This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. PATIENTS/METHODS: Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. RESULTS: Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p = .001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). CONCLUSION: The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Effects of Remifentanil Gradual Withdrawal Combined with Postoperative Infusion on Postoperative Hyperalgesia in Patients Undergoing Laparoscopic hysterectomy: A Factorial Design, Double-Blind, Randomized Controlled Trial.

Background: Remifentanil-induced hyperalgesia (RIH) increases the risk of persistent postoperative pain, making early postoperative analgesic therapy ineffective and affecting postoperative patient satisfaction. This study aimed to verify the effects of gradual withdrawal of remifentanil combined with postoperative pump infusion of remifentanil on postoperative hyperalgesia and pain in patients undergoing laparoscopic hysterectomy. Methods: This trial was a factorial design, double-blind, randomized controlled trial. Patients undergoing laparoscopic hysterectomy were randomly allocated to the control group, postoperative pump infusion of remifentanil group, gradual withdrawal of remifentanil group, or gradual withdrawal plus postoperative pump infusion of remifentanil group (n = 35 each). The primary outcome was postoperative mechanical pain thresholds in the medial forearm. The secondary outcomes included postoperative mechanical pain thresholds around the incision, pain numeric rating scale scores, analgesic utilization, awakening agitation or sedation scores, a 15-item quality of recovery survey, and postoperative complications. Results: Gradual withdrawal of remifentanil significantly increased postoperative pain thresholds versus abrupt discontinuation (P < 0.05), whereas postoperative infusion did not show significant differences compared to the absence of infusion (P > 0.05). The combined gradual withdrawal and postoperative infusion group exhibited the highest thresholds and had the lowest postoperative pain scores and analgesic requirements as well as the highest quality of recovery scores (P < 0.05). No significant differences were observed for agitation scores, sedation scores, or complication rates (P > 0.05). Conclusion: The novel combined gradual withdrawal and postoperative infusion of remifentanil uniquely attenuates postoperative hyperalgesia, pain severity, analgesic necessity, and improves recovery quality after laparoscopic hysterectomy.

Facial expressions of pain: the role of the serotonergic system.

RATIONALE: Although interest in the neurobiology of facial communication of pain has increased over the last decades, little is known about which neurotransmitter systems might be involved in regulating facial expressions of pain. OBJECTIVES: We aim to investigate whether the serotonergic system (5-HT), which has been implicated in various aspects of pain processing as well as in behavioral response inhibition, might play a role in facial expressions of pain. Using acute tryptophan depletion (ATD) to manipulate 5-HT function, we examined its effects on facial and subjective pain responses. METHODS: In a double-blind, placebo-controlled within-subject design, 27 participants received either an ATD or a control drink in two separate sessions. Approximately 5-h post-oral consumption, we assessed pain thresholds (heat, pressure) as well as facial and subjective responses to phasic heat pain. Moreover, situational pain catastrophizing and mood were assessed as affective state indicators. RESULTS: ATD neither influenced pain thresholds nor self-report ratings, nor catastrophizing or mood. Only facial responses were significantly affected by ATD. ATD led to a decrease in pain-indicative as well as in pain-non-indicative facial responses to painful heat, compared to the control condition. CONCLUSIONS: Decrease in brain 5-HT synthesis via ATD significantly reduced facial responses to phasic heat pain; possibly due to (i) diminished disposition to display social behavior or due to (ii) decreased facilitation of excitatory inputs to the facial motor neuron.

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.

Sensory, functional and electromyographic variables show different recovery patterns over a seven day period following exercise-induced pain in the hamstrings.

BACKGROUND: Delayed-onset muscle soreness (DOMS) is common after unaccustomed exercises and can restrict performance if intense physical activities are performed while the muscle is still sore. This study aimed to evaluate the recovery process following exercise-induced DOMS over a seven-day period by evaluating sensory, functional, and electromyographic parameters. METHODS: Twenty-four healthy males participated in four experimental sessions (Day-0, Day-2, Day-4, Day-7). Pain perception, pressure pain sensitivity, active range of motion, maximal isometric strength, and muscle activity of the hamstrings during the maximal isometric contraction were assessed bilaterally at each session. A single-leg deadlift eccentric exercise (5-sets of 20-reps) was performed at the end of Day-0 to induce DOMS in the dominant leg. FINDINGS: At Day-2, the DOMS-side showed increased pain sensitivity and decreased active range of motion, strength and muscle activity compared to Day-0 (P < 0.015). Muscle activity on the DOMS-side reached similar values than at baseline on Day-4, whereas pain perception, pressure pain sensitivity, maximal isometric strength, and active range of motion had returned to the baseline state on Day-7. No changes over time were observed on the control-side, showing all variables an excellent reliability between values at Day-0 and Day-7 (Intraclass Correlation Coefficient > 0.90). INTERPRETATION: Surface electromyographic values during a maximal isometric contraction recover faster than the other parameters. Given the heterogeneous path of altered variables towards DOMS recovery, trainers and clinicians should consider a multimodal assessment, including quantitative sensory and functional measures in addition to the subjective perception of recovery.

Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain.

OBJECTIVE: The aim was to study associations between chronic widespread pain, widespread pain sensitivity, leptin, and metabolic factors in individuals with knee pain. A secondary aim was to study these associations in a subgroup of individuals with normal BMI. METHOD: This cross-sectional study included 265 individuals. The participants were categorised into three different pain groups: Chronic widespread pain (CWP), chronic regional pain (ChRP), or no chronic pain (NCP). The pressure pain thresholds (PPTs) were assessed using computerised pressure algometry. Low PPTs were defined as having PPTs in the lowest third of all tender points. Leptin and metabolic factors such as BMI, visceral fat area (VFA), lipids, and glucose were also assessed. RESULT: Sixteen per cent reported CWP, 15% had low PPTs, and 4% fulfilled both criteria. Those who fulfilled the criteria for CWP were more often women, more obese, and had increased leptin levels. In logistic regression, adjusted for age and gender, leptin was associated with fulfilling criteria for CWP, OR 1.015 (95% CI 1.004-1.027, p = 0.008). In logistic regression, adjusted for age and gender, leptin was associated with low PPTs, OR 1.016 (95% CI 1.004-1.029, p = 0.012). Leptin was also associated with fulfilling both criteria, adjusted for age, sex, and visceral fat area (VFA), OR 1.030 (95% CI 1.001-1.060), p = 0.040. CONCLUSION: Leptin was associated with fulfilling the combined criteria for chronic widespread pain and low PPTs, even after adjusting for the visceral fat area (VFA). Longitudinal studies are needed to study the causal relationships between leptin and the development of widespread pain. TRIAL REGISTRATION: clinicalTrials.gov Identifier: NCT04928170.

Modulation of Pain Sensitivity by a Hyperventilatory Breathing Exercise and Cold Exposure Training.

Background: Evidence indicates that healthy individuals who follow a training program comprised hyperventilatory breathing exercises and cold exposure can voluntarily activate their sympathetic nervous system and attenuate their systemic inflammatory response during experimental endotoxemia (intravenous administration of bacterial endotoxin). Furthermore, trained participants reported less endotoxemia-induced flu-like symptoms. However, it remained to be determined whether the effects on symptoms are due to the mitigated inflammatory response or involve direct analgesic effects of (elements of) the training program. Methods: In the present study, we used Nijmegen-Aalborg Screening Quantitative sensory testing (NASQ) to objectively map pain sensitivity using non-invasive stimuli to address this question. First, NASQ parameters were evaluated in 20 healthy volunteers before, during, and after the conduct of the hyperventilatory breathing exercise. Second, NASQ measurements were performed before and after 48 healthy volunteers followed different modalities of the training program: breathing exercise training, cold exposure training, the combination of both, or no training. Lastly, NASQ measurements were performed in these 48 subjects during experimental endotoxemia. Results: Electrical pain detection thresholds increased during the breathing exercise (p = 0.001) as well as four hours afterwards (p = 0.03). Furthermore, cold exposure training resulted in lower VAS scores during hand immersion in ice water (p < 0.001). Systemic inflammation induced by administration of endotoxin nullified the decreased pain perception during the ice water test in subjects trained in cold exposure. Conclusion: A hyperventilatory breathing exercise decreases pain perception induced by an electrical stimulus. Furthermore, cold exposure training may decrease pain perception induced by hand immersion in ice water.

The role of spontaneous vs. experimentally induced attentional strategies for the pain response to a single bout of exercise in healthy individuals.

OBJECTIVES: Exercise-induced pain and exercise-induced hypoalgesia (EIH) are well described phenomena involving physiological and cognitive mechanisms. Two experiments explored whether spontaneous and instructed mindful monitoring (MM) were associated with reduced exercise-induced pain and unpleasantness, and increased EIH compared with spontaneous and instructed thought suppression (TS) in pain-free individuals. METHODS: Eighty pain-free individuals participated in one of two randomized crossover experiments. Pressure pain thresholds (PPTs) were assessed at the leg, back and hand before and after 15 min of moderate-to-high intensity bicycling and a non-exercise control condition. Exercise-induced pain and unpleasantness were rated after bicycling. In experiment 1 (n=40), spontaneous attentional strategies were assessed with questionnaires. In experiment 2, participants (n=40) were randomly allocated to use either a TS or MM strategy during bicycling. RESULTS: In experiment 1, the change in PPTs was significantly larger after exercise compared with quiet rest (p<0.05). Higher spontaneous MM was associated with less exercise-induced unpleasantness (r=-0.41, p<0.001), whereas higher spontaneous TS was associated with higher ratings of exercise-induced unpleasantness (r=0.35, p<0.05), but not with pain intensity or EIH. In experiment 2, EIH at the back was increased in participants using instructed TS compared with participants using instructed MM (p<0.05). CONCLUSIONS: These findings suggest that spontaneous and presumably habitual (or dispositional) attentional strategies may primarily affect cognitive-evaluative aspects of exercise, such as feelings of exercise-induced unpleasantness. MM was related to less unpleasantness, whereas TS was related to higher unpleasantness. In terms of brief experimentally-induced instructions, TS seems to have an impact on physiological aspects of EIH; however, these preliminary findings need further research.

Effects of conditioned pain modulation on Capsaicin-induced spreading muscle hyperalgesia in humans.

OBJECTIVES: Muscle pain can be associated with hyperalgesia that may spread outside the area of primary injury due to both peripheral and central sensitization. However, the influence of endogenous pain inhibition is yet unknown. This study investigated how endogenous pain inhibition might influence spreading hyperalgesia in experimental muscle pain. METHODS: Conditioned pain modulation (CPM) was assessed in 30 male volunteers by cold pressor test at the non-dominant hand as conditioning and pressure pain thresholds (PPT) at the dominant 2nd toe as test stimuli. Subjects were classified as having inhibitory or facilitating CPM based on published reference values. Subsequently, muscle pain and hyperalgesia were induced by capsaicin injection into the non-dominant supraspinatus muscle. Before and 5, 10, 15, 20, 30, 40, 50 and 60 min later, PPTs were recorded at the supraspinatus, infraspinatus and deltoid muscle, ring finger and toe. RESULTS: Compared to baseline, PPTs decreased at the supraspinatus, infraspinatus and deltoid muscle (p≤0.03), and increased at the finger and toe (p<0.001). In facilitating CPM (n=10), hyperalgesia occurred at 5, 10, 15, 20 and 40 min (p≤0.026). In inhibitory CPM (n=20), hyperalgesia only occurred after 10 and 15 min (p≤0.03). At the infraspinatus muscle, groups differed after 5 and 40 min (p≤0.008). CONCLUSIONS: The results suggest that facilitating CPM is associated with more spreading hyperalgesia than inhibitory CPM. This implies that poor endogenous pain modulation may predispose to muscle pain and spreading hyperalgesia after injury, and suggest that strategies to enhance endogenous pain modulation may provide clinical benefits.

Pressure Pain Thresholds and Central Sensitization in Relation to Psychosocial Predictors of Chronicity in Low Back Pain.

(1) Background: Peripheral, as well as central, sensitization have been described in chronic low back pain (cLBP). The purpose of this study is to investigate the influence of psychosocial factors on the development of central sensitization. (2) Methods: This prospective study investigated local and peripheral pressure pain thresholds and their dependence on psychosocial risk factors in patients with cLBP receiving inpatient multimodal pain therapy. Psychosocial factors were assessed using the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ). (3) Results: A total of 90 patients were included in the study, 61 (75.4% women, 24.6% men) of whom had significant psychosocial risk factors. The control group consisted of 29 patients (62.1% women, 37.9% men). At baseline, patients with psychosocial risk factors showed significantly lower local and peripheral pressure pain thresholds, suggesting central sensitization, compared to the control group. Sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), was also correlated with altered PPTs. After multimodal therapy, all participants reported increased local pain thresholds compared to at admission, independent of psychosocial chronification factors. (4) Conclusions: Psychosocial chronicity factors measured using the ÖMPSQ have a significant influence on pain sensitization in cLBP. A 14-day multimodal pain therapy increased local, but not peripheral, pressure pain thresholds.

The Immediate Hypoalgesic Effect of Low and High Force Thoracic Mobilizations in Asymptomatic Subjects as Measured by Pain Pressure Thresholds (PPT).

Physiotherapists commonly use mobilizations for treating patients with thoracic spine pain (TSP). There is evidence to suggest that spinal mobilizations can decrease pain. Different doses of mobilization treatment are applied, however there is a paucity of evidence on the influence of these dosage parameters. The effect of different forces of treatment remains unknown. This study aimed to investigate whether there was a difference in the hypoalgesic effect of high and low force thoracic mobilizations. This single-blinded, randomized, within-subject, repeated measures, cross-over design recruited 28 asymptomatic participants. Participants received the experimental conditions of high (200 N) and low force (30 N) mobilizations to T6 at least 48 h apart. Pressure pain thresholds (PPTs) were measured before and immediately after each experimental intervention at three different standardized sites. The results demonstrated that high force thoracic mobilizations caused a significant increase in PPT measures compared to low force mobilizations. This effect was detected at all PPT sites. This study suggests that high force thoracic PA mobilizations cause a significantly greater hypoalgesic response in asymptomatic participants than low force thoracic mobilizations. The hypoalgesic response seems to be elicited not only locally at the site of the intervention, but in a widespread manner.

Are catechol-O-methyltransferase gene polymorphisms genetic markers for pain sensitivity after all? - A review and meta-analysis.

The catechol-O-methyltransferase (COMT) gene has arguably been the designated pain sensitivity gene for nearly two decades. However, the literature provides inconsistent evidence. We performed several meta-analyses including k = 31 samples and n = 4631 participants thereby revealing small effects of rs4680 on pain thresholds in fibromyalgia, headache and across chronic pain conditions. Moreover, rs4680 effects were found across pain patients when affected, but not unaffected, body sites were assessed. No effect was detected for any other SNP investigated. Importantly, our results corroborate earlier findings in that we found a small effect of COMT haplotypes on pain sensitivity. Our review and meta-analysis contribute to the understanding of COMT-dependent effects on pain perception, provide insights into research issues and offer future directions. The results support the theory that rs4680 might only impact behavioural measures of pain when descending pain modulatory pathways are sufficiently challenged. After all, COMT polymorphisms are genetic markers of pain sensitivity, albeit with some limitations which are discussed with respect to their implications for research and clinical significance.

Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis.

OBJECTIVE: Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment. METHODS: Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment. RESULTS: This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1]). CONCLUSION: These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy.

Patients with neuropathic pain from lumbosacral radiculopathy demonstrate similar pressure pain thresholds and conditioned pain modulation to those with fibromyalgia.

OBJECTIVE: The purpose of the study was to evaluate pain thresholds, impairment of the endogenous pain modulatory system, and self-reported cognitive-emotional and central sensitization-related symptoms among three subject groups: a rarely studied patient cohort with neuropathic pain from lumbosacral radiculopathy (NPLSR), patients with fibromyalgia (FM) and healthy controls (HC). METHODS: Patient-reported pain-related symptomology was evaluated with psychometricallyvalidated questionnaires. Pressure pain threshold (PPT), heat pain threshold (HPT), and cold pain threshold (CPT) were assessed in the low back and contralateral forearm. Conditioned pain modulation (CPM) was evaluated with a recently introduced methodology that accounts for a standard error of measurement. RESULTS: Compared to the HC subjects, the FM and NPLSR subjects had significantly lower pain thresholds and more CPM impairment. No significant differences in PPT and CPM were observed between the FM and NPLSR groups. Significant group differences were found in self-reported symptoms of depression, anxiety, stress, and central sensitization. Self-reported symptom severity increased in a stair-step fashion, with the HC group scoring lowest and FM group scoring highest. CONCLUSION: The NPLSR group manifested CPM dysfunction and pressure hyperalgesia at similar levels to the FM group, indicating that these two chronic pain syndromes, likely based on different pathophysiological mechanisms, in fact share some common pain processing features. However, though both patient groups demonstrated similarities in pain processing, self-reported cognitive-emotional and central sensitization-related symptom severity was significantly higher in the FM cohort, which distinguished them from the chronic NPLSR cohort.

The effects of a 15-week physical exercise intervention on pain modulation in fibromyalgia: Increased pain-related processing within the cortico-striatal- occipital networks, but no improvement of exercise-induced hypoalgesia.

Dysfunctional top-down pain modulation is a hallmark of fibromyalgia (FM) and physical exercise is a cornerstone in FM treatment. The aim of this study was to explore the effects of a 15-week intervention of strengthening exercises, twice per week, supervised by a physiotherapist, on exercise-induced hypoalgesia (EIH) and cerebral pain processing in FM patients and healthy controls (HC). FM patients (n = 59) and HC (n = 39) who completed the exercise intervention as part of a multicenter study were examined at baseline and following the intervention. Following the exercise intervention, FM patients reported a reduction of pain intensity, fibromyalgia severity and depression. Reduced EIH was seen in FM patients compared to HC at baseline and no improvement of EIH was seen following the 15-week resistance exercise intervention in either group. Furthermore, a subsample (Stockholm site: FM n = 18; HC n = 19) was also examined with functional magnetic resonance imaging (fMRI) during subjectively calibrated thumbnail pressure pain stimulations at baseline and following intervention. A significant main effect of exercise (post > pre) was observed both in FM patients and HC, in pain-related brain activation within left dorsolateral prefrontal cortex and caudate, as well as increased functional connectivity between caudate and occipital lobe bordering cerebellum (driven by the FM patients). In conclusion, the results indicate that 15-week resistance exercise affect pain-related processing within the cortico-striatal-occipital networks (involved in motor control and cognition), rather than directly influencing top-down descending pain inhibition. In alignment with this, exercise-induced hypoalgesia remained unaltered.

A simple, bed-side tool to assess evoked pressure pain intensity.

OBJECTIVES: Existing equipment for quantitative sensory testing is generally expensive and not easily applicable in a clinical setting thus simple bed-side devices are warranted. Pressure hyperalgesia is a common finding in patients with musculoskeletal pain and an experimental model is delayed-onset muscle soreness (DOMS). DOMS is characterised by muscle hyperalgesia and some studies report facilitation of temporal summation of pain. This study aimed to detect DOMS induced muscle hyperalgesia and temporal summation of pain using a newly developed bed-side quantitative sensory testing device to deliver standardised pressure. METHODS: Twenty-two healthy participants participated in two sessions with the second session approximately 48 h after baseline. Pressure pain intensities were assessed from the gastrocnemius muscle with four probes calibrated to apply 2, 4, 6 and 8 kg, respectively. Temporal summation of pain (10 stimuli delivered at 0.5 Hz using the 6 kg probe) intensities were assessed from the same location. DOMS was evoked in the gastrocnemius muscle by an eccentric exercise. Sleepiness and physical activity were measured with the Epworth Sleepiness Scale and the Global Physical Activity Questionnaire to investigate if they were associated with the quantitative sensory testing measures. RESULTS: Pressure pain intensity was significantly increased 48 h after induction of DOMS when compared to baseline for all four probes (p<0.05). Temporal summation of pain was not statistically significant affected by DOMS and sleep quality and physical activity did not associate with any of the measures. CONCLUSIONS: This study introduces a simple, bed-side assessment tool for the assessment of pressure pain intensity and hence hyperalgesia and temporal summation of pain.

The Effects of Recovery Sleep on Experimental Pain.

Recent research suggests that recovery sleep (RS) has the potential to restore pain sensitivity and modulation after hyperalgesia due to preceding sleep deprivation. However, it has not yet been systematically examined whether the restoration of these pain parameters is driven by sleep characteristics of RS. Thus, the present study assessed changes in experimental pain during RS after total sleep deprivation (TSD) to test whether RS parameters predicted the restoration of the pain system. Thirty healthy participants completed one night of habitual sleep, one night of TSD and a subsequent recovery night. At-home sleep during baseline and recovery was assessed using portable polysomnography and a questionnaire. Before and after each night pressure pain thresholds (PPTs), temporal pain summation (TSP) and conditioned pain modulation (CPM) were assessed. PPTs decreased after TSD and increased following RS, indicating a restoration of pain sensitivity after hyperalgesia. RS characteristics did not predict this restoration, suggesting other mechanisms (eg, changes in serotonergic activity) underlying the observed pain changes. TSP indicated a lack of effect of experimental sleep manipulations on excitatory processes whereas CPM lacked sufficient reliability to investigate inhibitory processes. Thus, results indicate moderate effects of sleep manipulations on pain sensitivity, but not on pain modulation. PERSPECTIVE: This article highlights the potential of recovery sleep to let pain thresholds return to normal following their decrease after a night of total sleep deprivation. In contrast, endogenous pain modulation (temporal pain summation, conditioned pain modulation) was not affected by sleep deprivation and recovery sleep.

Effects of Percutaneous and Transcutaneous Electrical Nerve Stimulation on Endogenous Pain Mechanisms in Patients with Musculoskeletal Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: The main aim was to determine the effects of percutaneous electrical nerve stimulation (PENS) and transcutaneous electrical nerve stimulation (TENS) on endogenous pain mechanisms in patients with musculoskeletal pain. DESIGN: A systematic review and meta-analysis. METHODS: The search was conducted on March 1, 2022, in the EMBASE, CINAHL, PubMed, PEDro, Cochrane Library, Web of Science, Medline, and SCOPUS databases. Randomized controlled trials comparing the use of transcutaneous or percutaneous electrostimulation with a placebo, control group, or standard treatment in patients with musculoskeletal pain were included. Outcome measurements were quantitative sensory testing somatosensory variables like pressure pain threshold (PPT), conditioned pain modulation, and temporal summation of pain. The pooled data were evaluated in Review Manager 5.4. RESULTS: Twenty-four randomized controlled trials (n = 24) were included in the qualitative analysis and 23 in the meta-analysis. The immediate effects of PENS and TENS on local PPTs were significant, with a moderate effect size (standardized mean difference [SMD] 0.53; 95% confidence interval [CI]: 0.34 to 0.72; P < 0.00001). When only studies with a lower risk of bias were analyzed, the heterogeneity decreased from I2 = 58% (P < 0.00001) to I2 = 15% (P = 0.01), and a decrease in the overall effect was observed (SMD 0.33; 95% CI: 0.7 to 0.58). The short-term effects on local PPTs were not significant when compared with the control group (P = 0.13). The mid-term effects on local PPTs were significant, showing a large effect size (SMD 0.55; 95% CI: 0.9 to 1.00; P = 0.02). The immediate effects on conditioned pain modulation were significant, with a large effect size (SMD 0.94; 95% CI: 0.48 to 1.41; P < 0.0001). CONCLUSION: PENS and TENS have a mild-moderate immediate effect on local mechanical hyperalgesia in patients with musculoskeletal pain. It appears that these effects are not sustained over time. Analyses suggest an effect on central pain mechanisms producing a moderate increase in remote PPT, an increase in conditioned pain modulation, but further studies are needed to draw clearer conclusions.

Lean Mass is Associated with, but Does Not Mediate Sex Differences in Pressure Pain Sensitivity in Healthy Adults.

Background: Sex differences exist in pain sensitivity, however, the underlying mechanism(s) that explain these differences are not fully understood. Pain sensitivity has been shown to be influenced by body mass index, but limited data exist on the role of body composition on pain sensitivity. The purpose was to examine the influence of body composition on pain sensitivity in males and females. Methods: This cross-sectional study design used pressure pain thresholds (PPT) of 87 participants (45 female) who were assessed in the vastus lateralis (leg PPT) and brachioradialis (arm PPT) using a pressure algometer. Fat and lean tissue were assessed via dual-energy X-ray absorptiometry (DXA). A two group by two limb, repeated measured ANOVA was used to assess differences between limbs and sex. Spearman correlations and hierarchical regression analyses were employed to determine the association between body composition and PPT. Results: Males had higher PPTs then females (P<0.05) and had higher DXA assessed lean and lower levels fat mass (P<0.05). Total body and limb specific lean mass was associated with PPTs (r≥0.34; P<0.05). Hierarchical regression analysis revealed lean mass was a significant predictor of 8% of the variance in arm PPT (P<0.006) and 18% of the variance in leg PPT (P<0.001). However, lean mass was not found to statistically mediate the observed sex differences in PPT. Conclusion: This finding suggests lean mass may play a previously unknown role in sex differences in pressure pain sensitivity. Future studies are needed to confirm this finding and a larger sample size is likely required to have sufficient power to perform the mediation analysis.