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.

Physical Factors Associated with Non-Specific Neck Pain: Correlations Among Pain, Disability, Posture, Endurance, and Compensatory Movement.

BACKGROUND This study was conducted to investigate physical risk factors in patients with non-specific neck pain. The correlations among pain intensity, pressure pain threshold, range of motion (ROM), and disability index were analyzed in 50 patients with non-specific neck pain at a hospital in Korea. MATERIAL AND METHODS We enrolled 50 patients diagnosed with non-specific neck pain by a doctor. All subjects were evaluated for pain intensity, pressure threshold, degree of disability, active range of motion (ROM) of the neck, upper cervical rotation ROM, muscular endurance of deep cervical flexor, compensatory movements for neck flexion, forward head posture, shoulder height difference, and rounded shoulder posture. The correlation between each variable was analyzed. RESULTS Pain intensity had a significant correlation between cervical rotation ROM, cervical flexion-rotation ROM, rounded shoulder posture, shoulder height difference, and forward head posture (P<.05). There was a significant correlation between the pressure pain threshold and the cervical extension ROM, cervical flexion-rotation ROM, and rounded shoulder height (P<.05). The disability index had a significant correlation between the cervical rotation ROM, cervical flexion-rotation ROM, rounded shoulder posture, and the compensatory movement of neck flexion (P<.05). CONCLUSIONS Physical risk factors for non-specific neck pain included cervical rotation ROM, upper cervical rotation ROM, rounded shoulder posture, shoulder height difference, and cervical flexion compensatory movements, which can affect pain intensity and pressure pain threshold.

Post-polio syndrome - somatosensory dysfunction and its relation to pain: a pilot study with quantitative sensory testing.

OBJECTIVE: To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing. DESIGN: A cross-sectional, descriptive, pilot study conducted during 1 month. SUBJECTS/PATIENTS: Six patients with previously established post-polio syndrome and related chronic pain. METHODS: All subjects underwent a neurological examination including neuromuscular function, bedside sensory testing, a thorough pain anamnesis, and pain drawing. Screening for neuropathic pain was done with 2 questionnaires. A comprehensive Quantitative Sensory Testing battery was conducted with z-score transformation of obtained data, enabling comparison with published reference values and the creation of sensory profiles, as well as comparison between the study site (more polio affected extremity) and internal control site (less affected extremity) for each patient. RESULTS: Derived sensory profiles showed signs of increased prevalence of sensory aberrations compared with reference values, especially Mechanical Pain Thresholds, with significant deviation from reference data in 5 out of 6 patients. No obvious differences in sensory functions were seen between study sites and internal control sites. CONCLUSION: Post-polio syndrome may be correlated with a mechanical hyperalgesia/allodynia and might be correlated to a somatosensory dysfunction. With lack of evident side-to-side differences, the possibility of a generalized dysfunction in the somatosensory system might be considered.

Evaluation of the segmental distribution of pain sensitivity among patients with central sensitization associated with chronic subacromial pain syndrome: A cross-sectional study.

INTRODUCTION: Pain sensitivity is the main finding of central sensitization (CS) and can occur in patients with chronic shoulder pain. However, there is limited evidence concerning the distribution of pain sensitivity in shoulders, forearms, and legs in patients with CS associated with chronic shoulder pain. The present study aimed to determine the distribution of pain sensitivity in patients with CS associated with chronic subacromial pain syndrome (SPS). METHOD: This cross-sectional study included 58 patients with chronic SPS and CS (patient group) and 58 healthy participants (control group). The presence of CS was determined using the Central Sensitization Inventory (CSI). To determine the distribution of pain sensitivity, pressure pain threshold (PPT) measurements were performed from the shoulders, forearms, and legs. RESULTS: There was no significant difference between the two groups in terms of sociodemographic data (p > 0.05). The patient group had a significantly higher CSI score (p < 0.001) and lower PPTs in all regions (p < 0.05) than the control group. Unlike the control group, the patient group had lower PPTs on the affected side for the shoulder [mean difference (MD) 95% confidence interval (CI): 1.2 (-1.7 to -0.6)], forearm [MD 95% CI: 1.1 (-1.7 to -0.6)], and leg [MD 95% CI: 0.9 (-1.4 to -0.3)] compared with the contralateral side (p < 0.001). CONCLUSION: Pain sensitivity is more pronounced in the affected shoulder and the forearm and leg located on this side than in those on the contralateral side in patients with CS associated with chronic SPS.

Regional and widespread pain sensitivity decreases following stretching in both men and women - Indications of stretch-induced hypoalgesia.

INTRODUCTION: This study aimed to investigate the effect of sex on regional and widespread pain sensitivity following acute bouts of stretching and to investigate the acute effect of stretching on regional and widespread pain sensitivity following stretching. METHODS: 73 healthy adults (36 females; mean age 25.6 ± 6.7 years) with an age range from 19 to 62 years were recruited for this experimental study. Regional and distant pain pressure pain thresholds, passive knee extension range of motion and passive resistive torque were measured before and 30 s after four bouts of 30-s static muscle stretching of the knee flexors with 20-s rest between bouts. RESULTS: No significant sex differences were found for pressure pain thresholds (p > 0.132), range of motion (p = 0.446) or passive resistive torque (p = 0.559) between pre-stretch and post-stretch measures. There were significant increases in pressure pain thresholds (p = 0.010), range of motion (p = 0.001) and passive resistive torque (p = 0.007) between pre-stretch and post-stretch measures. CONCLUSION: Muscle stretching significantly decreased regional and widespread pain sensitivity, indicating that central pain-modulating mechanisms are engaged during muscle stretching, resulting in stretch-induced hypoalgesia. Moreover, the results showed that the effect of stretching on regional and widespread pain sensitivity is not sex-specific.

Multimodal sensorimotor assessment of hand and forearm asymmetries: a reliability and correlational study.

Background: Effective rehabilitation of upper limb musculoskeletal disorders requires multimodal assessment to guide clinicians' decision-making. Furthermore, a comprehensive assessment must include reliable tests. Nevertheless, the interrelationship among various upper limb tests remains unclear. This study aimed to evaluate the reliability of easily applicable upper extremity assessments, including absolute values and asymmetries of muscle mechanical properties, pressure pain threshold, active range of motion, maximal isometric strength, and manual dexterity. A secondary aim was to explore correlations between different assessment procedures to determine their interrelationship. Methods: Thirty healthy subjects participated in two experimental sessions with 1 week between sessions. Measurements involved using a digital myotonometer, algometer, inclinometer, dynamometer, and the Nine-Hole Peg test. Intraclass correlation coefficients, standard error of the mean, and minimum detectable change were calculated as reliability indicators. Pearson's correlation was used to assess the interrelationship between tests. Results: For the absolute values of the dominant and nondominant sides, reliability was 'good' to 'excellent' for muscle mechanical properties, pressure pain thresholds, active range of motion, maximal isometric strength, and manual dexterity. Similarly, the reliability for asymmetries ranged from 'moderate' to 'excellent' across the same parameters. Faster performance in the second session was consistently found for the Nine-Hole Peg test. No systematic inter-session errors were identified for the values of the asymmetries. No significant correlations were found between tests, indicating test independence. Conclusion: These findings indicate that the sensorimotor battery of tests is reliable, while monitoring asymmetry changes may offer a more conservative approach to effectively tracking recovery of upper extremity injuries.

The effect of resistance exercise on multimodal pain thresholds in local and systemic muscle sites.

Dynamic resistance exercise may produce reductions in pain locally at the exercising muscle and systemically at non-exercising sites. However, limited research has examined these changes with multiple noxious stimuli. This study examined changes in heat pain threshold (HPT) and pressure pain threshold (PPT) on different musculature after an upper and lower body exercise to compare local and systemic effects. A crossover design with 28 participants (mean age: 21 ± 4 years, 21 female) completed three sessions. Visit one included baseline quantitative sensory testing and 5-repetition maximum (RM) testing for upper (shoulder press) and lower (leg extension) body. In subsequent sessions, participants performed upper or lower body exercises using an estimated 75% 1-RM with pre/post assessment of HPT and PPT at three sites: deltoid, quadriceps, and low back. A significant three-way interaction was observed for HPT (F (1.71, 3.80) = 2.19, p = 0.036, η2p = 0.12) with significant increases in HPT over the quadriceps (p = 0.043) after leg extension and over the deltoid (p = 0.02) after shoulder press. Significant systemic changes were not observed for HPT or PPT. Local but not systemic effects were demonstrated after an acute bout of exercise. Peripheral pain sensitivity may be more responsive to heat stimuli after resistance exercise.

Temporal summation of second pain is affected by cognitive load.

This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtained from 21 healthy participants during the presentation of four experimental conditions that differed in the manipulation of attention to painful stimuli or working memory load (Attention to hand & TSSP; 0-back & TSSP (low cognitive load); 2-back & TSSP (high cognitive load); 2-back (without pain)). We found that the TSSP was reduced when the attention was diverted and the cognitive load increased, and this reduction was accompanied by higher midfrontal theta activity and lower posterior alpha and central beta activity. Although it is well established that TSSP is a phenomenon that occurs at the spinal level, here we show that it is also affected by supraspinal attentional mechanisms. Delivery of painful repeated stimuli did not affect the performance of the 2-back task but was associated with smaller amplitudes of attentional event-related potentials (ERPs) after standard stimuli (not the target). The study of brain activity during TSSP allowed to clarify the role of top-down attentional modulation in pain sensitization processes. Results contribute to a better understanding of cognitive dysfunction in pain conditions and reinforce the use of therapeutic strategies based on distracting attention away from pain.

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

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

A novel animal model for understanding secondary traumatic stress and visceral pain in male rats.

Empathetic relationships and the social transference of behaviours have been shown to occur in humans, and more recently through the development of rodent models, where both fear and pain phenotypes develop in observer animals. Clinically, observing traumatic events can induce 'trauma and stressor-related disorders' as defined in the DSM 5. These disorders are often comorbid with pain and gastrointestinal disturbances; however, our understanding of how gastrointestinal - or visceral - pain can be vicariously transmitted is lacking. Visceral pain originates from the internal organs, and despite its widespread prevalence, remains poorly understood. We established an observation paradigm to assess the impact of witnessing visceral pain. We utilised colorectal distension (CRD) to induce visceral pain behaviours in a stimulus rodent while the observer rodent observed. Twenty four hours post-observation, the observer rodent's visceral sensitivity was assessed using CRD. The observer rodents were found to have significant hyperalgesia as determined by lower visceral pain threshold and higher number of total pain behaviours compared with controls. The behaviours of the observer animals during the observation were found to be correlated with the behaviours of the stimulus animal employed. We found that observer animals had hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis, highlighted by reduced corticosterone at 90 minutes post-CRD. Using c-Fos immunohistochemistry we showed that observer animals also had increased activation of the anterior cingulate cortex, and decreased activation of the paraventricular nucleus, compared with controls. These results suggest that witnessing another animal in pain produces a behavioural phenotype and impacts the brain-gut axis.

Optimal Duration of Cold and Heat Compression for Forearm Muscle Biomechanics in Mixed Martial Arts Athletes: A Comparative Study.

BACKGROUND Cold and heat therapies for recovery in sports are commonly used, including in the mixed martial arts (MMA). The Game Ready (GR) device can be used for local monotherapy with either heat or cold and for contrast therapy. This study aimed to compare the effects of duration of cold and heat compression on biomechanical changes in the forearm muscles of 20 healthy mixed martial arts athletes. MATERIAL AND METHODS Twenty MMA volunteers (26.5±4.5 years old) underwent 3 different phases of the GR: (1) stimulation time 10 min (eGR-10, GR experimental group), (2) 10 min (cGR-10, sham control group) and (3) 20 min (eGR-20, GR experimental group). The following outcomes were assessed: muscle tone (T), stiffness (S), flexibility (E), pressure pain threshold (PPT), microvascular response (PU), and maximum isometric strength (Fmax). All measurements were performed before GR (rest) and after GR stimulation (post). RESULTS Both eGR-10 and eGR-20 significantly improved outcomes T (p<0.001), S (p<0.001), E (p=0.001, and p<0.001, respectively), PPT (p<0.001), PU (p<0.001), and Fmax (p<0.001). Notably, eGR-20 exhibited superior improvements in PU, Fmax, and PPT, with larger effect sizes (p<0.001). While eGR-10 demonstrated more pronounced reductions in T and S (p<0.001), these results underscore the potential for tailored GR therapy durations to optimize specific recovery goals for MMA athletes. CONCLUSIONS GR stimulation affects muscle biomechanical changes, pain threshold, muscle strength, and tissue perfusion. The study results suggest that 10 min of GR stimulation is sufficient to achieve changes that can be used to optimize recovery for MMA athletes.

Enhanced EEG power density during painful stretching in individuals with cerebral palsy.

BACKGROUND: Pain perception mechanisms in cerebral palsy remain largely unclear. AIMS: This study investigates brain activity in adults with cerebral palsy during painful and non-painful stretching to elucidate their pain processing characteristics. METHODS AND PROCEDURES: Twenty adults with cerebral palsy and 20 controls underwent EEG in three conditions: rest, non-painful stretching, and painful stretching. Time-frequency power density of theta, alpha, and beta waves in somatosensory and frontal cortices was analyzed, alongside baseline pressure pain thresholds. OUTCOMES AND RESULTS: Cerebral palsy individuals exhibited higher theta, alpha, and beta power density in both cortices during painful stretching compared to rest, and lower during non-painful stretching. Controls showed higher power density during non-painful stretching but lower during painful stretching. Cerebral palsy individuals had higher pain sensitivity, with those more sensitive experiencing greater alpha power density. CONCLUSIONS AND IMPLICATIONS: These findings confirm alterations in the cerebral processing of pain in individuals with cerebral palsy. This knowledge could enhance future approaches to the diagnosis and treatment of pain in this vulnerable population.

Effects of athletic tape on orofacial pain and jaw movements after 24 hours of use: a randomized clinical trial. / Efeitos da bandagem elástica na dor orofacial e nos movimentos mandibulares após 24 horas de uso: ensaio clínico randomizado.

PURPOSE: To analyze the sensation of pain and the range of mandibular movements of adult individuals with temporomandibular disorder, before and after the application of the athletic tape. METHOD: This is a double-blind randomized clinical trial, in which 22 adults with temporomandibular disorder participated, randomly allocated into two groups, with group A comprising 10 women and one man (mean age 28.2±8.3 years) and group B comprising nine women and two men (mean age 26.2±3.9 years). Group A was submitted to the application of the athletic tape on the masseter with 40% stretch and the group B to the application of the athletic tape on the masseter without stretching. All participants underwent the application of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Pain threshold assessment was performed using an algometer to apply pressure to measurement points. The measurement of mandibular movements was performed using a caliper. The athletic tape was glued using the I technique, with a fixed point over the insertion and a movable point over the origin of the masseter muscle. Participants remained with the athletic tape for 24 hours and were re-evaluated. RESULTS: There was pain relief in the group A in the temporomandibular joint on the right and at the origin of the masseter on the left. The group B showed a reduction in pain in the left anterior temporal region. No differences were found in mandibular movements after intervention, as well as no difference was found in the comparison by groups. CONCLUSION: The use of the athletic tape over the masseter muscle, with stretching, for 24 hours produced relief from the sensation of pain, on the origin of the right masseter and in the right temporomandibular joint, and, without stretching, in the left anterior temporal muscle. There was no difference in the range of mandibular movements.

OBJETIVO: Analisar a sensação de dor e amplitude dos movimentos mandibulares de indivíduos adultos com disfunção temporomandibular, antes e após aplicação da bandagem elástica por 24 horas. MÉTODO: Trata-se de um ensaio clínico randomizado duplo-cego, do qual participaram 22 sujeitos adultos com disfunção temporomandibular, alocados aleatoriamente em dois grupos, sendo grupo A composto por 10 mulheres e um homem (média de idade de 28,2±8,3 anos) e grupo B por nove mulheres e dois homens (média de idade de 26,2±3,9 anos). Todos os participantes foram submetidos à aplicação do Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Foi realizada a avaliação do limiar da dor, com uso de um algômetro, para aplicação da pressão no masseter e temporal e medição dos movimentos mandibulares, com paquímetro. O grupo A foi submetido à aplicação da bandagem sobre o músculo masseter com estiramento de 40% e o grupo B sem estiramento. A colagem da bandagem foi realizada, com corte em "I", com ponto fixo sobre a inserção e ponto móvel sobre a origem do músculo masseter. Os participantes permaneceram com a bandagem por 24 horas e foram reavaliados. RESULTADOS: Houve alívio da dor no grupo A na articulação temporomandibular à direita e na origem do masseter à esquerda. O grupo B apresentou redução da dor em região de temporal anterior à esquerda. Não foram encontradas diferenças nos movimentos mandibulares após intervenção, bem como não houve diferença na comparação entre os grupos. CONCLUSÃO: O uso da bandagem sobre o masseter, por 24 horas, com estiramento, produziu alívio da dor na origem do masseter direito e na região da articulação temporomandibular direita e, sem estiramento, no temporal anterior esquerdo. Não houve diferença na amplitude de movimentos mandibulares.

The role of self-reported and physiological stress in nocebo hyperalgesia.

Negative expectations can increase pain sensitivity, leading to nocebo hyperalgesia. However, the physiological and psychological factors that predispose individuals to this phenomenon are still not well understood. The present study examined whether stress induced by a social stressor affects nocebo hyperalgesia, and whether this effect is mediated by self-reported and physiological stress responses. We recruited 52 healthy participants (15 men) who were randomly assigned to either the Trier Social Stress Test (TSST) or a control condition (a friendly version of the TSST). Nocebo hyperalgesia was induced using negative suggestions combined with a validated pain conditioning paradigm. We assessed self-reported (anxiety and stress) and physiological (cortisol, alpha-amylase, heart rate, and skin conductance) responses to stress. Both groups exhibited significant nocebo hyperalgesia. The stress group showed higher levels of anxiety, self-reported stress, and cortisol levels compared to the control group while no significant differences were found in other physiological markers. The stress and control groups did not differ in the magnitude of nocebo hyperalgesia, but anxiety levels partially mediated the effects of the stress test on nocebo hyperalgesia. Our findings suggest that an external social stressor does not directly affect nocebo hyperalgesia, but that increased anxiety due to the stressor enhances its magnitude. Thus, it may be worthwhile to investigate whether reducing stress-related anxiety in clinical settings would help alleviate nocebo effects.

Oxidative stress plays an important role in the central regulatory mechanism of orofacial hyperalgesia under low estrogen conditions.

Hyperalgesia occurs in the orofacial region of rats when estrogen levels are low, although the specific mechanism needs to be investigated further. Furthermore, oxidative stress plays an important role in the transmission of pain signals. This study aimed to explore the role of oxidative stress in orofacial hyperalgesia under low estrogen conditions. We firstly found an imbalance between oxidative and antioxidant capacity within the spinal trigeminal subnucleus caudalis (SP5C) of rats after ovariectomy (OVX), resulting in oxidative stress and then a decrease in the orofacial pain threshold. To investigate the mechanism by which oxidative stress occurs, we used virus as a tool to silence or overexpress the excitatory amino acid transporter 3 (EAAT3) gene. Further investigation revealed that the regulation of glutathione (GSH) and reactive oxygen species (ROS) can be achieved by regulating EAAT3, which in turn impacts the occurrence of oxidative stress. In summary, our findings suggest that reduced expression of EAAT3 within the SP5C of rats in the low estrogen state may decrease GSH content and increase ROS levels, resulting in oxidative stress and ultimately lead to orofacial hyperalgesia. This suggests that antioxidants could be a potential therapeutic direction for orofacial hyperalgesia under low estrogen conditions, though more research is needed to understand its mechanism.

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

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

Association between myofascial trigger point therapy and conditioned pain modulation.

INTRODUCTION: Myofascial trigger point therapy (MTrP) is a widely used therapeutic approach, although the underlying mechanisms remain unclear. Mechanisms discussed include peripheral involvement of muscles as well as central pain modulating processes such as the conditioned pain modulation (CPM). The aim of this study was to investigate whether the analgesic response of MTrP and the analgesic response of CPM correlate in asymptomatic participants in order to identify shared underlying mechanisms of MTrP and CPM. METHOD: Both, CPM and MTrP protocols consisted of heat-based test stimuli (heat pain thresholds before and after the intervention) and pressure-based (conditioning) stimuli. Asymptomatic participants (n = 94) were randomly assigned to receive either mild, intense or no pressure stimuli (between-group design) to both the fingernail and the MTrP of the infraspinatus muscle (within-group design). Pressure stimuli at both locations (fingernail, MTrP) were applied with a pressure algometer for 120 s and continuously adjusted to maintain a constant pain intensity of mild or intense pain. All thermal stimuli were applied on the lower leg with a thermal stimulator. RESULTS: A significant correlation was shown between the analgesic effect of CPM and MTrP therapy for mild (r = 0.53, p = 0.002) and intensive stimuli (r = 0.73, p < 0.001). 17.3% of the variance of the MTrP effect were explained by CPM after mild stimulation, and 47.1% after intense stimulation. Pain-related characteristics did not explain the variance within the analgesic response using a regression analysis. CONCLUSIONS: Between the analgesic responses following MTrP and CPM paradigms, a moderate to strong correlation was observed, suggesting shared underlying mechanisms.

Hypoalgesia after aerobic exercise in healthy subjects: A systematic review and meta-analysis.

Exercise-Induced Hypoalgesia (EIH) refers to an acute reduced pain perception after exercise. This systematic review and meta-analysis investigated the effect of a single aerobic exercise session on local and remote EIH in healthy individuals, examining the role of exercise duration, intensity, and modality. Pressure pain thresholds (PPT) are used as the main measure, applying the Cochrane risk of bias tool and GRADE approach for certainty of evidence assessment. Mean differences (MD; Newton/cm²) for EIH effects were analysed. Thirteen studies with 23 exercises and 14 control interventions are included (498 participants). Most studies used bicycling, with only two including running/walking and one including rowing. EIH occurred both locally (MD = 3.1) and remotely (MD = 1.8), with high-intensity exercise having the largest effect (local: MD = 7.5; remote: MD = 3.0) followed by moderate intensity (local: MD = 3.1; remote: MD = 3.0). Low-intensity exercise had minimal impact. Neither long nor short exercise duration induced EIH. Bicycling was found to be effective in eliciting EIH, in contrast to the limited research observed in other modalities. The overall evidence quality was moderate with many studies showing unclear risk biases.

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

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

Exploring the mechanism of Nav1.3 in the ION-CCI rat model based on the TLR4/TRAF6/NF-κB pathway.

BACKGROUND: Trigeminal neuralgia (TN) is a common and difficult-to-treat neuropathic pain disorder in clinical practice. Previous studies have shown that Toll-like receptor 4 (TLR4) modulates the activation of the NF-κB pathway to affect neuropathic pain in rats. Voltage-gated sodium channels (VGSCs) are known to play an important role in neuropathic pain electrical activity. OBJECTIVE: To investigate whether TLR4 can regulate Nav1.3 through the TRAF6/NF-κB p65 pathway after infraorbital nerve chronic constriction injury (ION-CCI). STUDY DESIGN: ION-CCI modeling was performed on SD (Sprague Dawley) rats. To verify the success of the modeling, we need to detect the mechanical pain threshold and ATF3. Then, detecting the expression of TLR4, TRAF6, NF-κB p65, p-p65, and Nav1.3 in rat TG. Subsequently, investigate the role of TLR4/TRAF6/NF-κB pathway in ION-CCI model by intrathecal injections of LPS-rs (TLR4 antagonist), C25-140 (TRAF6 inhibitor), and PDTC (NF-κB p65 inhibitor). RESULTS: ION-CCI surgery decreased the mechanical pain threshold of rats and increased the expression of ATF3, TLR4, TRAF6, NF-κB p-p65 and Nav1.3, but there was no difference in NF-κB p65 expression. After inject antagonist or inhibitor of the TLR4/TRAF6/NF-κB pathway, the expression of Nav1.3 was decreased and mechanical pain threshold was increased. CONCLUSION: In the rat model of ION-CCI, TLR4 in the rat trigeminal ganglion regulates Nav1.3 through the TRAF6/NF-κB p65 pathway, and TLR4 antagonist alleviates neuropathic pain in ION-CCI rats.