Toll-Like Receptor 4 in Pain: Bridging Molecules-to-Cells-to-Systems.

Pain impacts the lives of billions of people around the world - both directly and indirectly. It is complex and transcends beyond an unpleasant sensory experience to encompass emotional experiences. To date, there are no successful treatments for sufferers of chronic pain. Although opioids do not provide any benefit to chronic pain sufferers, they are still prescribed, often resulting in more complications such as hyperalgesia and dependence. In order to develop effective and safe medications to manage, and perhaps even treat pain, it is important to evaluate novel contributors to pain pathologies. As such, in this chapter we review the role of Toll-like receptor 4, a receptor of the innate immune system, that continues to gain substantial attention in the field of pain research. Positioned in the nexus of the neuro and immune systems, TLR4 may provide one of the missing pieces in understanding the complexities of pain. Here we consider how TLR4 enables a mechanistical understanding of pain as a multidimensional biopsychosocial state from molecules to cells to systems and back again.

The Relationship Between Daily Physical Activity and Pain in Individuals with Knee Osteoarthritis.

OBJECTIVE: Investigate the association between physical activity and pain severity in individuals with knee osteoarthritis. DESIGN: Cross-sectional; systematic review with meta-analyses. METHODS: Thirty-one participants with knee osteoarthritis underwent assessment of symptoms via self-report questionnaires and quantitative sensory testing. Following testing, physical activity and symptoms were monitored for seven days using accelerometers and logbooks. Cross-correlation analyses were performed on fluctuations in symptoms and physical activity across the week to detect the relative timing of the strongest association between pain and activity. These data were complemented by meta-analyses of studies that examined correlations between pain from knee osteoarthritis and physical activity or fitness. RESULTS: Pain severity at baseline correlated with moderate to vigorous physical activity (r2 = 0.161-0.212, P < 0.05), whereby participants who were more physically active had less pain. Conversely, the peak of the cross-correlation analyses was most often positive and lagging, which indicated that pain was increased subsequent to periods of increased activity. These superficially discrepant findings were supported by the results of a meta-analysis of 13 studies and 9,363 participants, which identified significant heterogeneity for associations between physical activity and pain (I2 = 91%). Stronger inverse associations were found between fitness and pain. CONCLUSIONS: Associations between physical activity and pain in people with knee osteoarthritis are variable and dynamic. These results reflect the beneficial impact of an active lifestyle and accompanying higher fitness. Yet, the side effect of acute periods of physical activity to transiently exacerbate pain may influence the behavior of some people to avoid activity because of pain.

Exercise-based rehabilitation for cancer survivors with chemotherapy-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) affects up to 40% of cancer survivors and is associated with functional deficits and an increased falls incidence. There are presently no strongly recommended treatment strategies for CIPN. The aim of this study was to evaluate the impact of a multimodal exercise intervention on CIPN symptoms and related functional deficits, as well as neurophysiologic parameters. METHODS: All outcomes were assessed before and after an 8-week exercise intervention (3-weekly sessions) and preceding 8-week control period at baseline, pre-exercise and post-exercise. Outcome measures were objective and patient-reported CIPN, standing and dynamic balance, mobility, quality of life, and sensory and motor nerve excitability and conduction studies. RESULTS: Twenty-nine cancer survivors (8 male, 21 female; mean age 61.6 ± 11.8 years) with CIPN symptoms affecting function completed all assessments. Objective and patient-reported CIPN, dynamic balance, standing balance in eyes open conditions, mobility and quality of life were improved from pre- to post-exercise (4.0 < F < 10.2; p < .05), with no changes over the control period (p > .21). No changes were observed in sensory or motor neurophysiologic parameters (p > .23). CONCLUSIONS: This study provides encouraging evidence of the rehabilitative potential of multimodal exercise for persisting CIPN in a post-treatment cohort. Large randomised controlled trials are justified to confirm observed benefits and determine the mechanisms and clinical significance.

Aerobic Exercise Reduces Pressure More Than Heat Pain Sensitivity in Healthy Adults.

OBJECTIVES: The hypoalgesic effects of exercise are well described, but there are conflicting findings for different modalities of pain; in particular for mechanical vs thermal noxious stimuli, which are the most commonly used in studies of exercise-induced hypoalgesia. The aims of this study were 1) to investigate the effect of aerobic exercise on pressure and heat pain thresholds that were well equated with regard to their temporal and spatial profile and 2) to identify whether changes in the excitability of nociceptive pathways-measured using laser-evoked potentials-accompany exercise-induced hypoalgesia. SUBJECTS: Sixteen healthy adults recruited from the University of New South Wales. METHODS: Pressure and heat pain thresholds and pain ratings to laser stimulation and laser-evoked potentials were measured before and after aerobic cycling exercise and an equivalent period of light activity. RESULTS: Pressure pain thresholds increased substantially after exercise (rectus femoris: 29.6%, d = 0.82, P < 0.001; tibialis anterior: 26.9%, d = 0.61, P < 0.001), whereas heat pain thresholds did not (tibialis anterior: 4.2%, d = 0.30, P = 0.27; foot: 0.44%, d = 0.02, P = 1). Laser-evoked potentials and laser heat pain ratings also changed minimally after exercise (d = -0.59 to 0.3, P > 0.06). CONCLUSIONS: This is the first investigation to compare the effects of exercise on pressure and heat pain using the same stimulation site and pattern. The results show that aerobic exercise reduces mechanical pain sensitivity more than thermal pain sensitivity.

Barriers and facilitators of exercise experienced by cancer survivors: a mixed methods systematic review.

PURPOSE: Exercise has been shown to improve the health and well-being of people who have survived cancer. Yet, less than 40% of cancer survivors in Australia meet the recommended 150 min of moderate-intensity physical activity per week. Our objective was to systematically review the literature regarding barriers, facilitators and preferences for exercise for survivors of cancer. METHOD: MEDLINE, EMBASE, CINAHL, PsycINFO and Scopus were searched for qualitative and quantitative articles addressing barriers, facilitators and preferences for exercise in cancer survivors. Quality assessment was performed by two independent reviewers using the Mixed Methods Appraisal Tool. Thomas and Harden's method of thematic synthesis was used to amalgamate qualitative data while descriptive statistics were used to collate quantitative data. RESULTS: Nineteen studies were included (9 qualitative and 10 quantitative). Persisting treatment-related side effects was the most commonly reported barrier to initiating or maintaining exercise, followed by lack of time and fatigue. The most common facilitators of exercise were gaining a feeling of control over their health as well as managing emotions and mental well-being, while the preferred method of exercise was walking. We also identified a lack of useful information provided to survivors regarding exercise. CONCLUSION: Treatment-related side effects, lack of time and fatigue were key barriers to exercise for survivors of varied cancer types. Insufficient patient education may contribute to the belief that exercise is not helpful when experiencing side effects of treatment, including fatigue. Identifying barriers and facilitators leads to improved support and education from health professionals which is required to provide safe and effective exercise recommendations for survivors.

Arm posture-dependent changes in corticospinal excitability are largely spinal in origin.

Biceps brachii motor evoked potentials (MEPs) from cortical stimulation are influenced by arm posture. We used subcortical stimulation of corticospinal axons to determine whether this postural effect is spinal in origin. While seated at rest, 12 subjects assumed several static arm postures, which varied in upper-arm (shoulder flexed, shoulder abducted, arm hanging to side) and forearm orientation (pronated, neutral, supinated). Transcranial magnetic stimulation over the contralateral motor cortex elicited MEPs in resting biceps and triceps brachii, and electrical stimulation of corticospinal tract axons at the cervicomedullary junction elicited cervicomedullary motor evoked potentials (CMEPs). MEPs and CMEPs were normalized to the maximal compound muscle action potential (Mmax). Responses in biceps were influenced by upper-arm and forearm orientation. For upper-arm orientation, biceps CMEPs were 68% smaller (P= 0.001), and biceps MEPs 31% smaller (P= 0.012), with the arm hanging to the side compared with when the shoulder was flexed. For forearm orientation, both biceps CMEPs and MEPs were 34% smaller (both P< 0.046) in pronation compared with supination. Responses in triceps were influenced by upper-arm, but not forearm, orientation. Triceps CMEPs were 46% smaller (P= 0.007) with the arm hanging to the side compared with when the shoulder was flexed. Triceps MEPs and biceps and triceps MEP/CMEP ratios were unaffected by arm posture. The novel finding is that arm posture-dependent changes in corticospinal excitability in humans are largely spinal in origin. An interplay of multiple reflex inputs to motoneurons likely explains the results.

Stability of biceps brachii MMax with one session of strength training.

INTRODUCTION: The maximal compound muscle action potential (Mmax ) of biceps brachii is altered by 1 session of strength training. We examined whether the number of training sets in a session plays a role in this effect. METHODS: Ten subjects completed 1 session of isometric strength training of the elbow flexors (2 sets, 75% maximal force with 1 arm; 12 sets with the other). Biceps Mmax was acquired in both arms before training, immediately after training, and every 5 min for 30 min. RESULTS: Mmax area was initially potentiated after 2 (7.2%) and 12 sets (13.6%) but returned to baseline within 5 min. CONCLUSIONS: Biceps Mmax is similarly affected by 2 and 12 sets of strength training. The overall effect is minimal compared with ∼25% depression reported after similar training in a different arm posture. Thus, changes in Mmax appear more dependent on training posture than number of training sets. Muscle Nerve 54: 791-793, 2016.

Limited Association Between Aerobic Fitness and Pain in Healthy Individuals: A Cross-Sectional Study.

OBJECTIVE: In healthy individuals and people with chronic pain, an inverse association between physical activity level and pain has been reported. Associations between objectively measured fitness and pain have also been found in people with chronic pain, but it is not clear whether the same relations are apparent in healthy individuals. The purpose of the present study was to examine the relation between aerobic capacity and pain in healthy individuals. METHODS: Pressure pain threshold, ischemic pain tolerance, and pain ratings during ischemia were assessed and analyzed in relation to aerobic capacity in 35 healthy individuals. Correlation and multiple linear regression were used to analyze the data. Data from previous similar studies in healthy individuals and people with fibromyalgia were extracted and collated by literature review to support interpretation of the experimental data. RESULTS: No relation was found between aerobic capacity and any measure of pain, with the exception of a moderate inverse association between aerobic capacity and lower body pressure pain threshold in males (r = -0.58, P = 0.03) when data from male and female participants were analyzed separately. The limited association between aerobic capacity and quantitative sensory testing of pain was consistent with the data synthesis from previous studies of healthy individuals but differed from studies of people with fibromyalgia. CONCLUSIONS: Aerobic capacity is unrelated to pain in healthy young adults. For people with chronic pain, the negative relation between aerobic capacity and pain presumably arises from the underlying pathophysiology and/or associated behaviors of the disease process.

eLearning improves allied health professionals' knowledge and confidence to manage medically unexplained chronic fatigue states: A randomized controlled trial.

OBJECTIVES: To evaluate the impact of eLearning by allied health professionals on improving the knowledge and confidence to manage people with medically unexplained chronic fatigue states (FS). METHODS: Using a parallel randomized controlled trial design, participants were randomized 1:1 to a 4-week eLearning or wait-list control group. Knowledge and self-reported confidence in clinical skills to implement a therapeutic intervention for patients with FS were assessed at baseline, post-intervention and follow-up. Secondary outcomes (adherence and satisfaction with online education, knowledge retention) were also assessed. Data was analyzed using intention-to-treat. RESULTS: There were 239 participants were randomized (eLearning n = 119, control n = 120), of whom 101 (85%) eLearning and 107 (89%) control participants completed baseline assessments and were included in the analysis. Knowledge (out of 100) improved significantly more in the eLearning group compared to the control group [mean difference (95% CI) 8.6 (5.9 to 11.4), p < 0.001]. Knowledge was reduced in the eLearning group at follow-up but was still significantly higher than baseline [6.0 (3.7 to 8.3), p < 0.001]. Median change (out of 5) in confidence in clinical skills to implement the FS intervention was also significantly greater in the eLearning group compared to the control group [knowledge: eLearning (1.2), control (0); clinical skills: eLearning (1), control (0.1); both p < 0.001)]. Average time spent on the eLearning program was 8.8 h. Most participants (80%) rated the lesson difficulty as at the "right level", and 91% would recommend it to others. CONCLUSIONS: eLearning increased knowledge and confidence to manage FS amongst allied health professionals and was well-accepted. REGISTRATION: ACTRN12616000296437 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370222&isReview=true.

The effectiveness of activity pacing interventions for people with chronic fatigue syndrome: a systematic review and meta-analysis.

PURPOSE: To investigate whether activity pacing interventions (alone or in conjunction with other evidence-based interventions) improve fatigue, physical function, psychological distress, depression, and anxiety in people with chronic fatigue syndrome (CFS). MATERIALS AND METHODS: Seven databases were searched until 13 August 2022 for randomised controlled trials that included activity pacing interventions for CFS and a validated measure of fatigue. Secondary outcomes were physical function, psychological distress, depression, and anxiety. Two reviewers independently screened studies by title, abstract and full text. Methodological quality was evaluated using the PEDro scale. Random-effects meta-analyses were performed in R. RESULTS: 6390 articles were screened, with 14 included. Good overall study quality was supported by PEDro scale ratings. Activity pacing interventions were effective (Hedges' g (95% CI)) at reducing fatigue (-0.52 (-0.73 to -0.32)), psychological distress (-0.37 (-0.51 to -0.24)) and depression (-0.29 (-0.49 to -0.09)) and improving physical function (mean difference 7.18 (3.17-11.18)) when compared to no treatment/usual care. The extent of improvement was greater for interventions that encouraged graded escalation of physical activities and cognitive activities. CONCLUSION: Activity pacing interventions are effective in reducing fatigue and psychological distress and improving physical function in CFS, particularly when people are encouraged to gradually increase activities. REGISTRATION: PROSPERO CRD42016036087. IMPLICATIONS FOR REHABILITATIONA key feature of chronic fatigue syndrome (CFS) is a prolonged post-exertional exacerbation of symptoms following physical activities or cognitive activities.Activity pacing is a common strategy often embedded in multi-component management programs for CFS.Activity pacing interventions are effective in reducing fatigue and psychological distress and improving physical function in CFS, particularly when patients are encouraged to gradually increase their activities.Healthcare professionals embedding activity pacing as part of treatment should work collaboratively with patients to ensure successful, individualised self-management strategies.

One immune system plays many parts: The dynamic role of the immune system in chronic pain and opioid pharmacology.

The transition from acute to chronic pain is an ongoing major problem for individuals, society and healthcare systems around the world. It is clear chronic pain is a complex multidimensional biological challenge plagued with difficulties in pain management, specifically opioid use. In recent years the role of the immune system in chronic pain and opioid pharmacology has come to the forefront. As a highly dynamic and versatile network of cells, tissues and organs, the immune system is perfectly positioned at the microscale level to alter nociception and drive structural adaptations that underpin chronic pain and opioid use. In this review, we highlight the need to understand the dynamic and adaptable characteristics of the immune system and their role in the transition, maintenance and resolution of chronic pain. The complex multidimensional interplay of the immune system with multiple physiological systems may provide new transformative insight for novel targets for clinical management and treatment of chronic pain. This article is part of the Special Issue on "Opioid-induced changes in addiction and pain circuits".

Training-induced modifications of corticospinal reactivity in severely affected stroke survivors.

When permitted access to the appropriate forms of rehabilitation, many severely affected stroke survivors demonstrate a capacity for upper limb functional recovery well in excess of that formerly considered possible. Yet, the mechanisms through which improvements in arm function occur in such profoundly impaired individuals remain poorly understood. An exploratory study was undertaken to investigate the capacity for brain plasticity and functional adaptation, in response to 12-h training of reaching using the SMART Arm device, in a group of severely affected stroke survivors with chronic upper limb paresis. Twenty-eight stroke survivors were enroled. Eleven healthy adults provided normative data. To assess the integrity of ipsilateral and contralateral corticospinal pathways, transcranial magnetic stimulation was applied to evoke responses in triceps brachii during an elbow extension task. When present, contralateral motor-evoked potentials (MEPs) were delayed and reduced in amplitude compared to those obtained in healthy adults. Following training, contralateral responses were more prevalent and their average onset latency was reduced. There were no reliable changes in ipsilateral MEPs. Stroke survivors who exhibited contralateral MEPs prior to training achieved higher levels of arm function and exhibited greater improvements in performance than those who did not initially exhibit contralateral responses. Furthermore, decreases in the onset latency of contralateral MEPs were positively related to improvements in arm function. Our findings demonstrate that when severely impaired stroke survivors are provided with an appropriate rehabilitation modality, modifications of corticospinal reactivity occur in association with sustained improvements in upper limb function.

Inequities in access to pediatric epilepsy surgery: a bioethical framework.

Epilepsy is a common childhood condition associated with a considerable medical and psychosocial burden. Children in whom medical treatment fails to reduce seizure burden represent an especially vulnerable patient population because prolonged, uncontrolled seizures are associated with poor developmental and neurocognitive outcomes. Surgical treatment in the form of cortical resection, functional disconnection, or neuromodulation may alleviate or significantly reduce the disease burden for a subset of these patients. However, there remains a dichotomy between the perceived benefits of surgery and the implementation of surgical strategies in the management of medically intractable epilepsy. The current paper presents an analysis of the bioethical implications of existing inequities in access to pediatric epilepsy surgery that result from inconsistent referral practices and discrepant evaluation techniques. The authors provide a basic bioethical framework composed of 5 primary expectations to inform public, institutional, and personal policies toward the provision of epilepsy surgery to afflicted children.

The effect of exercise intensity on exercise-induced hypoalgesia in cancer survivors: A randomized crossover trial.

Pain is experienced by people with cancer during treatment and in survivorship. Exercise can have an acute hypoalgesic effect (exercise-induced hypoalgesia; EIH) in healthy individuals and some chronic pain states. However, EIH, and the moderating effect of exercise intensity, has not been investigated in cancer survivors. This study examined the effect of low- and high-intensity aerobic exercise on EIH in cancer survivors after a single exercise session as well as a brief period of exercise training (2-weeks, three exercise sessions per week). Participants (N = 19) were randomized to low- (30%-40% Heart Rate Reserve (HRR) or high- (60%-70% HRR) intensity stationary cycling for 15-20 min. Pressure pain thresholds (PPT) were assessed over the rectus femoris and biceps brachii before and after a single exercise session and again after a short training period at the assigned intensity. Then, following a 6-week washout period, the intervention was repeated at the other intensity. After the first exercise session, high-intensity exercise resulted in greater EIH over the rectus femoris than low intensity (mean difference ± SE: -0.51 kg/cm2  ± 0.15, Cohen's d = 0.78, p = 0.004). After a 2-week training period, we found no difference in EIH between intensities (0.01 kg/cm2  ± 0.25, d = 0.00 p = 0.99), with comparable moderate effect sizes for both low- and high-intensity exercise, indicative of EIH. No EIH was observed over the biceps brachii of the arm at either low or high intensity. Low-intensity exercise training may be a feasible option to increase pain thresholds in cancer survivors.

The Associations Between Physical Activity, Sleep, and Mood with Pain in People with Parkinson's Disease: An Observational Cross-Sectional Study.

BACKGROUND: Pain is common in Parkinson's disease (PD). In general and chronic pain populations, physical inactivity, poor sleep, and anxiety are associated with worse pain. However, little is known about these potential predictors of pain in PD. OBJECTIVE: This cross-sectional observational study investigated associations between measures of physical activity, sleep, and mood with pain in people with PD. METHODS: Pain was measured using the King's PD Pain Scale and the Brief Pain Inventory (pain severity and interference) in 52 participants with PD. Independent variables were categorised by demographics (age, gender), disease severity (MDS-UPDRS) and duration, central sensitization (Central Sensitization Inventory), physical activity (Incidental and Planned Exercise Questionnaire), sleep (Pittsburgh Sleep Quality Index), and mood (Hospital Anxiety and Depression Scale). RESULTS: Univariate regression analyses showed that increased disease severity, longer disease duration, greater central sensitization, increased physical activity, poor sleep, anxiety, and depression were associated with worse pain in one or more pain measures (p < 0.05). Multivariate regression models accounted for 56% of the variance in the King's Pain Scale, 25% pain severity and 36% in pain interference. Poor sleep independently contributed to worse pain scores in all models (ß 0.3-0.4, p < 0.05). CONCLUSION: Increased physical activity, poor sleep, anxiety, and depression are associated with worse pain scores in people with PD. For optimal management of pain in people with PD, sleep and mood may need to be addressed. Further, the nature of the relationship between physical activity and pain in PD requires further investigation.

Common input to different regions of biceps brachii long head.

The purpose of the experiment was to compare the level of synchronization exhibited by pairs of motor units located within and between functionally distinct regions of the biceps brachii muscle. Pairs of single motor units were recorded from seven subjects using separate electrodes located in the lateral and medial aspects of the long head of biceps brachii. Participants were required to exert a combination of flexion and supination torques so that both motor units discharged at approximately 10 pps for >/=200 s and the level of motor unit synchronization could be quantified. When motor unit recordings were sufficiently stable at the completion of this synchrony task, a series of ramp contractions with multiple combinations of flexion and supination torques were performed to characterize the recruitment thresholds of the motor units. Common input strength (CIS) was significantly greater (P < 0.01) for the within-region pairs of motor units (0.28 extra sync. imps/s, n = 26) than for the between-region pairs (0.13 extra sync. imps/s, n = 18), but did not differ significantly for the 12 within-region pairs from the lateral head and 14 from the medial head (0.27 vs. 0.29 extra sync. imps/s; P = 0.83). Recruitment thresholds were measured for 33 motor units, but there was only a weak association between CIS and the respective recruitment patterns for motor unit pairs (n = 9). The present investigation provides evidence of a differential distribution of synaptic input across the biceps brachii motor neuron pool, but this appears to have minimal association with the recruitment patterns for individual motor units.

Exercise-induced hypoalgesia is present in people with Parkinson's disease: Two observational cross-sectional studies.

BACKGROUND: Exercise is prescribed for people with Parkinson's disease to address motor and non-motor impairments, including pain. Exercise-induced hypoalgesia (i.e., an immediate reduction in pain sensitivity following exercise) is reported in the general population; however, the immediate response of pain sensitivity to exercise in people with Parkinson's disease is unknown. The purpose of this study was to investigate if exercise-induced hypoalgesia is present following isometric and aerobic exercise in people with Parkinson's disease, and if so, if it varies with the dose of aerobic exercise. METHODS: Thirty people with idiopathic Parkinson's disease and pain-free age-matched controls completed two observational studies evaluating the response to: (a) right arm isometric exercise; and (b) treadmill walking at low and moderate intensities. Pressure pain thresholds were measured over biceps brachii and quadriceps muscles immediately before and after exercise, with increased thresholds after exercise indicating exercise-induced hypoalgesia. RESULTS: Pressure pain thresholds increased in the Parkinson's disease group at all tested sites following all exercise bouts (e.g., isometric exercise, right bicep 29%; aerobic exercise, quadriceps, moderate intensity 8.9%, low intensity 7.1% (p ≤ 0.008)), with no effect of aerobic exercise dose (p = 0.159). Similar results were found in the control group. CONCLUSIONS: Overall, people with Parkinson's disease experienced an exercise-induced hypoalgesia response similar to that of the control group, the extent of which did not vary between mild and moderate doses of aerobic exercise. Further research is warranted to investigate potential longer term benefits from exercise in the management of pain in this population. SIGNIFICANCE: Isometric and aerobic exercise reduces pain sensitivity in people with Parkinson's disease. As exercise is important for people with Parkinson's disease, these results provide assurance that people with Parkinson's disease and pain can exercise without an immediate increase in pain sensitivity. The reduction in pain sensitivity with both modes and with low and moderate intensities of aerobic exercise suggests that people with Parkinson's disease can safely choose the mode and intensity of exercise that best suits their needs.

The development and electronic delivery of case-based learning using a fast healthcare interoperability resource system.

HL7 International's Fast Healthcare Interoperability Resources (FHIR) standard provides a common format for sharing health data (eg, FHIR resources) and a RESTful Application Programming Interface (eg, FHIR API) for accessing those resources via a FHIR server connected to an electronic health record system or any other system storing clinical data. Substitutable Medical Applications and Reusable Technologies (SMART) leverages FHIR to create an electronic health record (EHR) agnostic app platform. It utilizes the OAuth standard to provide for authorization and authentication. This paper describes the development and informal evaluation of Case Based Learning on FHIR (CBL on FHIR), a prototype EHR-connected FHIR/SMART platform to provide interactive digital cases for use in medical education. The project goals were to provide a more interactive form of CBL than is possible on paper to more realistically simulate clinical decision making and to expose medical students to modern informatics systems and tools for use in patient care.

A spinal pathway between synergists can modulate activity in human elbow flexor muscles.

Electrical stimulation of the brachioradialis branch of the radial nerve has been shown to inhibit the discharge of voluntarily activated motor units in biceps brachii during weak contractions with the elbow flexor muscles. The purpose of the present study was to characterise the inhibitory reflex by comparing its strength in the short and long heads of the biceps brachii and examining the influence of forearm position on the strength of the reflex. Spike-triggered stimulation was used to assess the influence of radial nerve stimulation on the discharge of single motor units in the biceps brachii of 15 subjects. Stimulation of the radial nerve prolonged the interspike interval (P < 0.001) of motor units in the long (n = 31, 4.8 +/- 5.6 ms) and short heads (n = 26, 8.1 +/- 12.3 ms) of biceps brachii with no difference between the two heads (P = 0.11). The strength of inhibition varied with forearm position for motor units in both heads (n = 18, P < 0.05). The amount of inhibition was greatest in pronation (7.9 +/- 8.9 ms), intermediate in neutral (5.8 +/- 7.1 ms), and least in supination (2.8 +/- 3.4 ms). These findings indicate that the inhibition evoked by afferent feedback from brachioradialis to low-threshold motor units (mean force 3-5% MVC) in biceps brachii varied with forearm posture yet was similar for the two heads of biceps brachii. This reflex pathway provides a mechanism to adjust the activation of biceps brachii with changes in forearm position, and represents a spinal basis for a muscle synergy in humans.

Accessory muscle activity contributes to the variation in time to task failure for different arm postures and loads.

Time to failure and electromyogram activity were measured during two types of sustained submaximal contractions with the elbow flexors that required each subject to exert the same net muscle torque with the forearm in two different postures. Twenty men performed the tasks, either by maintaining a constant force while pushing against a force transducer (force task), or by supporting an equivalent load while maintaining a constant elbow angle (position task). The time to failure for the position task with the elbow flexed at 1.57 rad and the forearm horizontal was less than that for the force task (5.2 +/- 2.6 and 8.8 +/- 3.6 min, P = 0.003), whereas it was similar when the forearm was vertical (7.9 +/- 4.1 and 7.8 +/- 4.5 min, P = 0.995). The activity of the rotator cuff muscles was greater during the position tasks (25.1 +/- 10.1% maximal voluntary contraction) compared with the force tasks (15.2 +/- 5.4% maximal voluntary contraction, P < 0.001) in both forearm postures. However, the rates of increase in electromyogram of the accessory muscles and mean arterial pressure were greater for the position task only when the forearm was horizontal (P < 0.05), whereas it was similar for the elbow flexors. These findings indicate that forearm posture influences the difference in the time to failure for the two fatiguing contractions. When there was a difference between the two tasks, the task with the briefer time to failure involved greater rates of increase in accessory muscle activity and mean arterial pressure.