Multifocal tDCS Targeting the Motor Network Modulates Event-Related Cortical Responses During Prolonged Pain

Multifocal transcranial direct current stimulation (tDCS) targeting several brain regions is promising for inducing cortical plasticity. It remains unknown whether multifocal tDCS aimed at the resting-state motor network (network-tDCS) can revert N2-P2 cortical responses otherwise attenuated during prolonged experimental pain. Thirty-eight healthy subjects participated in 2 sessions separated by 24 hours (Day1, Day2) of active (n = 19) or sham (n = 19) network-tDCS. Experimental pain induced by topical capsaicin was maintained for 24 hours and assessed using a numerical rating scale. Electrical detection and pain thresholds, and N2-P2 evoked potentials (electroencephalography) to noxious electrical stimulation were recorded before capsaicin-induced pain (Day1-baseline), after capsaicin application (Day1-post-cap), and after 2 sessions of network-tDCS (Day2). Capsaicin induced moderate pain at Day1-post-cap, which further increased at Day2 in both groups (P = .01). Electrical detection/pain thresholds did not change over time. N2-P2 responses were reduced on Day1-post-cap compared to Day1-baseline (P = .019). At Day2 compared with Day1-post-cap, N2-P2 responses were significantly higher in the Active network-tDCS group (P<.05), while the sham group remained inhibited. These results suggest that tDCS targeting regions associated with the motor network may modulate the late evoked brain responses to noxious peripheral stimulation otherwise initially inhibited by capsaicin-induced pain.PerspectiveThis study extends the evidence of N2-P2 reduction due to capsaicin-induced pain from 30 minutes to 24 hrs. Moreover, 2 sessions of tDCS targeting the motor network in the early stage of nociceptive pain may revert the inhibition of N2-P2 associated with capsaicin-induced pain.     

Exercise-Induced Hypoalgesia Profile in Rats Predicts Neuropathic Pain Intensity Induced by Sciatic Nerve Constriction Injury

The aim of this study was to investigate the predictive value of exercise-induced hypoalgesia (EIH) profile on pain intensity induced by nerve injury in a rat model. EIH was tested by evaluating the percentage of withdrawal responses to a train of 30 mechanical stimuli on the hind paw before and after 180 seconds of exercise on a rotating rod. The rats were grouped into low, medium, and high EIH based on their reduction in the percentage of withdrawal responses before and after exercise. Rats from each group then underwent left sciatic nerve constriction injury. Mechanical allodynia, mechanical hyperalgesia, and heat allodynia were assessed in the affected and contralateral hind paws prior to and 3 and 7 days following the procedure. The low EIH rats demonstrated increased hypersensitivity at baseline and developed significantly more severe heat allodynia, mechanical allodynia, and hyperalgesia 3 and 7 days following the injury compared to the medium and high EIH rats. Moreover, the low EIH rats developed contralateral heat allodynia following the injury. The EIH of habituated and nonhabituated rats was compared to study the role of stress on the hypoalgesic effect. No significant differences were found between the habituated and nonhabituated rats at baseline and 1 and 5 minutes after the exercise.PerspectiveEIH profile was found to be predictive of pain severity following nerve injury. It may suggest that selected patients with faulty pain modulation are at risk for developing chronic pain following injury or surgical procedures. EIH may represent a preoperative means to detect this predisposition and enable proactive management.     

The Effect of Theta Burst Stimulation Over the Primary Motor Cortex on Experimental Hamstring Pain: A Randomized,Controlled Study

Theta burst stimulation (TBS) over the primary motor cortex (M1) is an emerging technique that may have utility in the treatment of musculoskeletal pain. However, previous work exploring the analgesic effects of noninvasive brain stimulation has been limited largely to the arm or hand, despite 80% of acute musculoskeletal injuries occurring in the lower limb. This is a pertinent point, given the functional and neurophysiological differences between upper and lower limb musculature, as well as evidence suggesting that reorganization of corticomotor pathways is region-specific. This study investigated the effect of excitatory TBS on pain, function, and corticomotor organization during experimentally induced lower limb pain. Twenty-eight healthy participants attended 2 experimental sessions. On Day 0, participants completed 10 sets of 10 maximal eccentric contractions of the right hamstring muscles to induce delayed onset muscle soreness. Four consecutive blocks of either active or sham TBS were delivered on Day 2. Measures of mechanical sensitivity, pain (muscle soreness, pain intensity, pain area) function (single-leg hop distance, maximum voluntary isometric contraction, lower extremity functional scale), and corticomotor organization were recorded before and after TBS on Day 2. Pain and function were also assessed daily from Days 2 to 10. Active TBS reduced mechanical sensitivity compared to sham stimulation (P = .01). Corticomotor organization did not differ between groups, suggesting that improvements in mechanical sensitivity were not mediated by changes in M1. Subjective reports of pain intensity and function did not change following active TBS, contrasting previous reports in studies of the upper limb.PerspectiveM1 TBS reduces mechanical sensitivity associated with experimentally induced hamstring pain. Though further work is needed, these findings may hold important implications for those seeking to expedite recovery or reduce muscle sensitivity following hamstring injury.     

Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesized that the spatial and temporal manifestations of EIH and CPM were comparable. The participants were 80 healthy subjects (40 females), between 18 and 65 years of age in this randomized, repeated-measures cross-over trial that involved data collection on 2 different days. CPM was assessed by 2 different cold pressor tests (hand and foot). EIH was assessed by 2 intensities of aerobic bicycling exercises and 2 intensities of isometric muscle contraction exercises (arm and leg). Pressure pain thresholds (PPTs) were recorded before, during, after, and 15 minutes after conditioning/exercise at sites local to and remote from the extremity used for cold pressor stimulation and exercise. PPTs increased at local as well as at remote sites during both cold pressor tests and after all of the exercise conditions except low-intensity bicycling. EIH after bicycling was higher in women than in men. CPM and the EIH responses after isometric exercises were comparable in men and women and were not affected by age. The EIH response was larger in the exercising body part compared with nonexercising body parts for all exercise conditions. High-intensity exercise produced greater EIH responses than did low-intensity exercise. The change in PPTs during cold pressor tests and the change in PPTs after exercises were not correlated. The CPM response was not dominated by local manifestations, and the effect was seen only during the stimulation, whereas exercise had larger local manifestations, and the effects were also found after exercise.     

Exercise-Induced Hypoalgesia in Healthy Individuals and People With Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis

Exercise-induced hypoalgesia (EIH) is a reduction in pain that occurs during or following exercise. Randomized controlled studies published from 1980 to January 2020 that examined experimentally induced pain before and during/following a single bout of exercise in healthy individuals or people with chronic musculoskeletal pain were systematically reviewed. Data were analyzed using random-effects meta-analyses and studies were appraised using the Cochrane Risk of Bias tool and GRADE. Five thousand eight hundred twenty-nine records were screened, with 13 studies ultimately included. In healthy individuals, aerobic exercise caused large EIH (7 studies, 236 participants; g = ?.85 [?1.58, ?.13]), dynamic resistance exercise caused small EIH (2 studies, 23 participants; g = ?.45 [?.69, ?.22]), and isometric exercise did not cause EIH (3 studies, 177 participants; g = ?.16 [?.36,.05]). In chronic musculoskeletal pain, isometric exercise did not cause EIH (3 studies, 114 participants; g = ?.41 [?1.08,.25]); aerobic (0 studies) and dynamic resistance (1 study) exercise were not analyzed. We conclude that, based on small studies with unclear risk of bias, aerobic and dynamic resistance exercise reduce experimental pain in healthy individuals. Further research is needed to determine whether EIH exists for experimental and clinical pain in people with chronic musculoskeletal pain.Registration: PROSPERO ID: CRD42018085886.PerspectiveBased on low-quality data from small samples, a single bout of aerobic exercise reduces experimental pain in healthy individuals. The evidence is unclear in people with chronic musculoskeletal pain but warrants further investigation due to the limited number of studies in these populations.     

Contralateral attenuation of pain after short-duration submaximal isometric exercise.

Only a small amount of research has been conducted examining whether exercise-induced hypoalgesia (EIH) occurs after isometric exercise. Thus, the purpose of this investigation was to examine whether EIH occurred in women after short-duration submaximal isometric exercise and whether the responses were restricted to the exercised hand (ipsilateral) or also occurred in the nonexercised (contralateral) hand. Fourteen healthy women (mean age = 19.5 years) completed 2 sets of submaximal (40% to 50% of max) isometric exercise consisting of squeezing a dynamometer for 2 minutes with the dominant hand. A pressure stimulus was applied to the forefinger on the dominant and nondominant hands for 2 minutes before and after isometric exercise. Participants pressed a button when the stimulus became painful, indicating pain threshold (PT), and also rated the intensity of the stimulus every 15 seconds, using a pain rating scale (PR). Results indicated that there were significant trials effects (P < .05) for PT and PR, but the main effect for hands was not significant (P > .05). PTs were found to be elevated, whereas PRs were reduced for both hands after isometric exercise. It is concluded that submaximal isometric exercise performed for 2 minutes resulted in ipsilateral and contralateral hypoalgesic responses. PERSPECTIVE: The findings from the present study demonstrated that short-duration nonexhaustive isometric exercise was associated with hypoalgesic responses in the exercised and nonexercised hands. It appears that short-duration submaximal isometric exercise resulted in generalized (ie, ipsilateral and contralateral) pain-inhibitory responses in healthy young women.     

Effects of local pressure and vibration on muscle pain from eccentric exercise and hypertonic saline

In human subjects the triceps surae of one leg was exercised eccentrically by asking subjects to walk backwards on an inclined treadmill. Before the exercise controlled local pressure, applied to the muscle with an electromagnet, produced mild soreness, which was reduced when the pressure was combined with vibration. When delayed-onset muscle soreness (DOMS) had set in, 24-48 h after the exercise, vibration increased pain from local pressure. Vibrating at different frequencies suggested 80 Hz as the optimal frequency. During 2-h testing post-exercise, evidence of a change in character of the effects of vibration was first detected at 6 h. It persisted up to 72 h post-exercise. When muscle pain was generated in an unexercised triceps by injection of hypertonic (5%) saline, controlled local pressure applied to the sore area increased pain levels by 32% while pressure plus vibration reduced this to 11%. In a subject with DOMS, local pressure again increased pain from saline by 32% but combining it with vibration increased pain further by an additional 20%. The effect of vibration on DOMS could be abolished with a large nerve fibre block applied to the sciatic nerve. It is concluded that the vibration effects are the result of stimulation of large-diameter mechanoreceptive afferents in the muscle which, it is speculated, play a role in generating DOMS.     

The clinical effectiveness of therapeutic massage for musculoskeletal pain: a systematic review

Objectives

To determine the effectiveness of therapeutic massage (TM) for the symptomatic relief of musculoskeletal pain, and to analyse TM intervention protocols used in studies.

Design

Systematic review of randomised controlled clinical trials and experimental studies on healthy human participants.

Participants

Patients with musculoskeletal pain and healthy participants with post-exercise pain and soreness.

Main outcome measures

Comparisons of TM with: (i) no treatment; (ii) sham interventions; and (iii) active (standard) treatment. Outcome was dichotomised as effective (TM > comparison group) or not effective (TM ≤ comparison group).

Results

Twenty studies (1341 participants) met the criteria for review. TM was superior to no treatment in five out of 10 comparisons, superior to sham (laser) treatment in one out of two comparisons, and superior to active treatment in seven out of 22 comparisons. TM was superior to comparison groups in six out of 11 studies using patients with musculoskeletal pain, and in three out of seven studies using patients with low back pain. TM was superior to comparison groups in four out of nine studies using healthy participants experiencing post-exercise pain and soreness. There were no relationships between study outcome and the TM regimen used.

Conclusions

The available evidence is inconclusive. A combination of inadequate sample sizes, low methodological quality and insufficient TM dosing is likely to have contributed to the confused evidence base.     

tDCS modulates cortical nociceptive processing but has little to no impact on pain perception

Transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. Several studies suggest clinical efficacy in chronic pain syndromes. However, little is known regarding its effects on cortical pain processing. In this double-blind, randomized, cross-over, sham controlled study, we examined the effects of anodal, cathodal, and sham stimulation of the left motor cortex in 16 healthy volunteers using functional imaging during an acute heat pain paradigm as well as pain thresholds, pain intensity ratings, and quantitative sensory testing. tDCS was applied at 1 mA for 15 minutes. Neither cathodal nor anodal tDCS significantly changed brain activation in response to nociceptive stimulation when compared with sham stimulation. However, contrasting the interaction of stimulation modes (anodal/cathodal) resulted in a significant decrease of activation in the hypothalamus, inferior parietal cortex, inferior parietal lobule, anterior insula, and precentral gyrus, contralateral to the stimulation site after anodal stimulation, which showed the opposite behavior after cathodal stimulation. Pain ratings and heat hyperalgesia showed only a subclinical pain reduction after anodal tDCS. Larger-scale clinical trials using higher tDCS intensities or longer durations are necessary to assess the neurophysiological effect and subsequently the therapeutic potential of tDCS.     

Effectiveness of Transcranial Direct Current Stimulation Combined With Exercising in People With Fibromyalgia: A Randomized Sham-Controlled Clinical Trial

ObjectiveTo evaluate the effectiveness of transcranial direct current stimulation (tDCS) combined with exercising in people with fibromyalgia.DesignRandomized, triple-blind, sham-controlled, clinical trial.SettingPrimary health care center.ParticipantsA total of 120 volunteer participants (N=120) between 18 and 65 years old and diagnosed with fibromyalgia. Four participants dropped out of the study for causes unrelated to the intervention.InterventionParticipants were randomized into 3 groups (active tDCS+exercising, sham tDCS+exercising, no-intervention control). The intervention was delivered in 5 sessions over 2 weeks.Main Outcome MeasuresPain intensity and referred pain area after suprathreshold pressure stimulation.ResultsPain intensity further decreased in the active tDCS group vs control (mean, ?14.43; 95% confidence interval, ?25.27 to ?3.58) at post intervention, unlike the sham tDCS group. Both tDCS groups did not achieve greater reductions in referred pain vs control. In the active tDCS group, health status (mean, ?14.80; 95% confidence interval, ?23.10 to ?6.50) and pain catastrophizing (mean, ?6.68, 95% confidence interval, ?11.62 to ?1.73) improved at post intervention, and so did health status (mean, ?8.81; 95% confidence interval, ?17.11 to ?0.51), pain catastrophizing (mean, ?7.00; 95% confidence interval, ?12.13 to ?1.87), and depression (mean, ?3.52; 95% confidence interval, ?6.86 to ?0.19) after 1 month. In the sham tDCS group, improvements were recorded in health status (mean, ?13.21; 95% confidence interval, ?21.52 to ?4.91) and depression (mean, ?3.35; 95% confidence interval, ?6.35 to ?0.35) at post intervention and in health status (mean, ?8.77; 95% confidence interval, ?17.06 to ?0.47), pain catastrophizing (mean, ?5.68; 95% confidence interval, ?10.80 to ?0.55), and depression (mean, ?3.98; 95% confidence interval, ?7.31 to ?0.64) after 1 month. No intergroup differences were observed between active and sham tDCS.ConclusionsActive and sham tDCS improved health status, pain catastrophizing, and depression vs control, but pain intensity decreased only in the active tDCS group.     

Prophylactic tolperisone for post-exercise muscle soreness causes reduced isometric force--a double-blind randomized crossover control study.

The role of tolperisone hydrochloride, a centrally acting muscle relaxant in relieving painful muscle spasm is recently being discussed. The present study hypothesizes that the prophylactic use of tolperisone hydrochloride may effectively relieve post-exercise muscle soreness, based on the spasm theory of exercise pain. Twenty male volunteers, aged 25.2 +/- 0.82 years (mean +/- SEM) participated in 10 sessions in which they received oral treatment with placebo or the centrally acting muscle relaxant tolperisone hydrochloride (150 mg) three times daily for 8 days, in randomized crossover double-blind design. Time course assessments were made for pressure pain threshold, Likert's pain score (0-5), pain areas, range of abduction, isometric force, and electromyography (EMG) root mean square (RMS) during maximum voluntary isometric force on day 1 and 6, immediately after an eccentric exercise of first dorsal interosseous muscle, and 24 and 48 h after the exercise. Treatment with placebo or tolperisone hydrochloride was initiated immediately after the assessments on the first day baseline assessments. On the sixth day baseline investigations were repeated and then the subjects performed six bouts of standardized intense eccentric exercise of first dorsal interosseous muscle for provocation of post-exercise muscle soreness (PEMS). Perceived intensity of warmth, tiredness, soreness and pain during the exercise bouts were recorded on a 10 cm visual analogue pain scale. VAS scores and pressure pain thresholds did not differ between tolperisone and placebo treatment. All VAS scores increased during the exercise bouts 2, 3, 4, 5 and 6 as compared to bout 1. Increased pain scores and pain areas were reported immediately after, 24 and 48 h after exercise. Pressure pain thresholds were reduced at 24 and 48 h after the exercise in the exercised hand. Range of abduction of the index finger was reduced immediately after the exercise and was still reduced at 24 h as compared to the non-exercised hand. The EMG RMS amplitude was also reduced immediately after the exercise, but was increased at 24 and 48 h. Isometric force was reduced immediately after the exercise as compared to days 1, 6, and the 24 and 48 h post-exercise assessments with a greater reduction following the tolperisone hydrochloride treatment and the reduction was more in tolperisone group as compared to the placebo group. The results suggest, that the prophylactic intake of tolperisone hydrochloride provides no relief to pain in course of post-exercise muscle soreness but results in reduction in isometric force.     

Exercise-Induced Hypoalgesia in Pain-Free and Chronic Pain Populations: State of the Art and Future Directions

Exercise is considered an important component of effective chronic pain management and it is well-established that long-term exercise training provides pain relief. In healthy, pain-free populations, a single bout of aerobic or resistance exercise typically leads to exercise-induced hypoalgesia (EIH), a generalized reduction in pain and pain sensitivity that occurs during exercise and for some time afterward. In contrast, EIH is more variable in chronic pain populations and is more frequently impaired; with pain and pain sensitivity decreasing, remaining unchanged or, in some cases, even increasing in response to exercise. Pain exacerbation with exercise may be a major barrier to adherence, precipitating a cycle of physical inactivity that can lead to long-term worsening of both pain and disability. To optimize the therapeutic benefits of exercise, it is important to understand how EIH works, why it may be impaired in some people with chronic pain, and how this should be addressed in clinical practice. In this article, we provide an overview of EIH across different chronic pain conditions. We discuss possible biological mechanisms of EIH and the potential influence of sex and psychosocial factors, both in pain-free adults and, where possible, in individuals with chronic pain. The clinical implications of impaired EIH are discussed and recommendations are made for future research, including further exploration of individual differences in EIH, the relationship between exercise dose and EIH, the efficacy of combined treatments and the use of alternative measures to quantify EIH.PerspectiveThis article provides a contemporary review of the acute effects of exercise on pain and pain sensitivity, including in people with chronic pain conditions. Existing findings are critically reviewed, clinical implications are discussed, and recommendations are offered for future research.     

增生疗法联合经颅直流电刺激治疗膝骨性关节炎疼痛的临床疗效观察

目的:观察增生疗法联合经颅直流电刺激治疗膝骨性关节炎疼痛的效果并探讨其作用机制。方法:选取膝骨性关节炎患者42例作为研究对象，随机分成观察组和对照组各21例。2组各有1例脱落，最终各20例完成研究。2组均给予增生治疗，即20%高渗葡萄糖8ml关节内注射，每周1次，共3次。观察组再给以电流强度为2mA的经颅直流电刺激治疗，每天1次，每次20min,持续2周；对照组也给予电刺激治疗。但每次仅在治疗开始和结束时各提供15s的2mA电流刺激以模拟真刺激的体感知觉，其余时间无电流刺激，每天1次，每次20min,持续2周。分别于治疗前、第1次增生治疗后2、4、6周，采用视觉模拟评分(VAS)、西安大略和麦克马斯特大学骨关节炎指数(WOMAC)、压痛阈(PPT)和条件性疼痛调制(CPM)对患者的膝关节功能活动及疼痛情况进行评估。结果:治疗前，2组患者的VAS、WOMAC、PPT及CPM比较均无统计学差异。在第1次增生治疗后的2、4、6周，观察组患者的VAS评分较同时间点对照组降低，CPM较同时间点对照组升高(均P<0.05);2组患者的VAS、WOMAC均较治疗前降低(均P<0.05),...     

Anodal Transcranial Direct Current Stimulation Reduces Secondary Hyperalgesia Induced by low Frequency Electrical Stimulation in Healthy Volunteers

The aim of the study was to determine whether transcranial direct current stimulation (tDCS) reduced pain and signs of central sensitization induced by low frequency electrical stimulation in healthy volunteers. Thirty-nine participants received tDCS stimulation under 4 different conditions: anodal tDCS of the primary motor cortex (M1), anodal tDCS of the dorsolateral prefrontal cortex (DLPFC), anodal tDCS over M1 and DLPFC concurrently, and sham tDCS. Participants were blind to the tDCS condition. The order of the conditions was randomized among participants. Pain ratings to pinpricks, the current level that evoked moderate pain, and pain induced by low frequency electrical stimulation were assessed in the forearm by an experimenter who was blind to the tDCS conditions. Anodal tDCS at M1 increased the current level that evoked moderate pain compared to sham and other conditions. Anodal tDCS of DLPFC completely abolished secondary hyperalgesia. Unexpectedly, however, concurrent anodal tDCS over M1 and DLPFC did not reduce pain or hyperalgesia more than M1 alone or DLPFC alone. Overall, these findings suggest that anodal tDCS over M1 suppresses pain, and that anodal tDCS over DLPFC modulates secondary hyperalgesia (a sign of central sensitization) in healthy participants.PerspectiveAnodal transcranial current stimulation (atDCS) at the left motor cortex and the dorsolateral prefrontal cortex increased the electrically-evoked pain threshold and reduced secondary hyperalgesia in healthy participants. Replication of this study in chronic pain populations may open more avenues for chronic pain treatment.     

tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine

Objective.— We investigated in a sham‐controlled trial the analgesic effects of a 4‐week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high‐resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation. Methods.— Thirteen patients with chronic migraine were randomized to receive 10 sessions of active or sham tDCS for 20 minutes with 2 mA over 4 weeks. Data were collected during baseline, treatment and follow‐up. For the tDCS computational analysis, we adapted a high‐resolution individualized model incorporating accurate segmentation of cortical and subcortical structures of interest. Results.— There was a significant interaction term (time vs group) for the main outcome (pain intensity) and for the length of migraine episodes (ANOVA, P < .05 for both analyses). Post‐hoc analysis showed a significant improvement in the follow‐up period for the active tDCS group only. Our computational modeling studies predicted electric current flow in multiple cortical and subcortical regions associated with migraine pathophysiology. Significant electric fields were generated, not only in targeted cortical regions but also in the insula, cingulate cortex, thalamus, and brainstem regions. Conclusions.— Our findings give preliminary evidence that patients with chronic migraine have a positive, but delayed, response to anodal tDCS of the primary motor cortex. These effects may be related to electrical currents induced in pain‐related cortical and subcortical regions.     

Effects of motor cortex modulation and descending inhibitory systems on pain thresholds in healthy subjects

Pain modulation can be achieved using neuromodulatory tools that influence various levels of the nervous system. Transcranial direct current stimulation (tDCS), for instance, has been shown to reduce chronic pain when applied to the primary motor cortex. In contrast to this central neuromodulatory technique, diffuse noxious inhibitory controls (DNIC) refers to endogenous analgesic mechanisms that decrease pain following the introduction of heterotopic noxious stimuli. We examined whether combining top-down motor cortex modulation using anodal tDCS with a bottom-up DNIC induction paradigm synergistically increases the threshold at which pain is perceived. The pain thresholds of 15 healthy subjects were assessed before and after administration of active tDCS, sham tDCS, cold-water-induced DNIC, and combined tDCS and DNIC. We found that both tDCS and the DNIC paradigm significantly increased pain thresholds and that these approaches appeared to have additive effects. Increase in pain threshold following active tDCS was positively correlated with baseline N-acetylaspartate in the cingulate cortex and negatively correlated with baseline glutamine levels in the thalamus as measured by magnetic resonance spectroscopy. These results suggest that motor cortex modulation may have a greater analgesic effect when combined with bottom-up neuromodulatory mechanisms, presenting new avenues for modulation of pain using noninvasive neuromodulatory approaches. PERSPECTIVE: This article demonstrates that both noninvasive motor cortex modulation and a descending noxious inhibitory controls paradigm significantly increase pain thresholds in healthy subjects and appear to have an additive effect when combined. These results suggest that existing pain therapies involving DNIC may be enhanced through combination with noninvasive brain stimulation.     

Mechanisms of Exercise-Induced Hypoalgesia

The purpose of this study was to examine opioid and endocannabinoid mechanisms of exercise-induced hypoalgesia (EIH). Fifty-eight men and women (mean age = 21 years) completed 3 sessions. During the first session, participants were familiarized with the temporal summation of heat pain and pressure pain protocols. In the exercise sessions, following double-blind administration of either an opioid antagonist (50 mg naltrexone) or placebo, participants rated the intensity of heat pulses and indicated their pressure pain thresholds and pressure pain ratings before and after 3 minutes of submaximal isometric exercise. Blood was drawn before and after exercise. Results indicated that circulating concentrations of 2 endocannabinoids, N-arachidonylethanolamine and 2-arachidonoylglycerol, as well as related lipids oleoylethanolamide, palmitoylethanolamide, N-docosahexaenoylethanolamine, and 2-oleoylglycerol, increased significantly (P < .05) following exercise. Pressure pain thresholds increased significantly (P < .05), whereas pressure pain ratings decreased significantly (P < .05) following exercise. Also, temporal summation ratings were significantly lower (P < .05) following exercise. These changes in pain responses did not differ between the placebo and naltrexone conditions (P > .05). A significant association was found between EIH and docosahexaenoylethanolamine. These results suggest involvement of a nonopioid mechanism in EIH following isometric exercise.PerspectiveCurrently, the mechanisms responsible for EIH are unknown. This study provides support for a potential endocannabinoid mechanism of EIH following isometric exercise.     

Acupuncture can be beneficial for exercise-induced muscle soreness: A randomised controlled trial

IntroductionStrenuous physical exercise may cause acute muscle soreness (AMS), which occurs directly after exercise, as well as delayed onset muscle soreness (DOMS), which occurs about 24 h after exercise. Studies of acupuncture's effect on DOMS have had contradictory results, whereas its effect on AMS has not been extensively studied. The main goal of this study was to evaluate acupuncture's effects on AMS and DOMS and on the prevention of DOMS.Method45 volunteers were randomised into a verum acupuncture group, a sham acupuncture group and a control group. After exercise-induced muscle damage was elicited, muscle soreness and pressure pain threshold were assessed at different time points. The outcome assessments were performed before (T1) and 20 min after the first acupuncture treatment (T2); then, 24 h later, they were performed before (T3) and 20 min after the second acupuncture treatment (T4). In the verum and sham acupuncture groups, acupuncture was performed for 2 min, immediately after T1 and T3 assessments, whereas subjects in the control group simply rested for 2 min without treatment. Verum acupuncture was given at ST34, ST36 and LR3, whereas sham acupuncture was given at three nontraditional points. Results: We found that verum acupuncture can reduce the occurrence of AMS by one-half and DOMS by one-third. We also found specific and nonspecific acupuncture effects in AMS and DOMS.ConclusionThe uneven induction of muscle damage identified by our study, as shown by heterogeneity in pressure pain threshold values, may have led to the contradictory results in published studies on DOMS.     

Short vs. long length of rectus femoris during eccentric exercise in relation to muscle damage in healthy males

BACKGROUND: We investigated the effects of short vs. long length of rectus femoris during eccentric exercise of similar range of motion on selected muscle damage indicators. METHODS: Using an isokinetic dynamometer at 1.05 rad/s, 12 healthy male [mean (standard deviation), 21 (2) years] volunteers randomly underwent two exercise sessions, one on each leg, 14 days apart. During each session, subjects had to accomplish 12 sets of 10 maximal voluntary efforts in seated and prone positions to achieve short and long length of rectus femoris, respectively. Muscle damage indicators [serum creatine kinase activity, delayed onset muscle soreness, range of motion, eccentric peak torque, concentric peak torque and isometric peak torque] were assessed pre-exercise and 24, 48, 72 as well as 96 h post-exercise. FINDINGS: Compared to baseline data, creatine kinase, delayed onset muscle soreness, and range of motion disclosed significant changes at all time points after both exercise sessions (P<0.05). However, these muscle damage indicators demonstrated greater changes following exercise at short compared to long length of rectus femoris (P<0.05). Torque assessments also revealed that nine out of 12 and only two out of 12 measurements decreased significantly following short and long length eccentric exercise of rectus femoris, respectively (P<0.05). Short length eccentric exercise resulted in greater torque declines compared to long length during concentric and isometric evaluations (P<0.05). No such differences were observed when torque changes were evaluated eccentrically. INTERPRETATION: Short length of rectus femoris eccentric exercise induces greater muscle damage and peak torque declines than the corresponding long length in healthy adults.