Left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation reduces the development of long-term muscle pain

The left dorsolateral prefrontal cortex (DLPFC) is involved in the experience and modulation of pain, and may be an important node linking pain and cognition. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC can reduce chronic and experimental pain. However, whether left DLPFC rTMS can influence the development of chronic pain is unknown. Using repeated intramuscular injection of nerve growth factor to induce the development of sustained muscle pain (lasting weeks), 30 healthy individuals were randomized to receive 5 consecutive daily treatments of active or sham left DLPFC rTMS, starting before the first nerve growth factor injection on day 0. Muscle soreness and pain severity were collected daily for 14 days and disability on every alternate day. Before the first and 1 day after the last rTMS session, anxiety, depression, affect, pain catastrophizing, and cognitive performance on the attention network test were assessed. Left DLPFC rTMS treatment compared with sham was associated with reduced muscle soreness, pain intensity, and painful area (P < 0.05), and a similar trend was observed for disability. These effects were most evident during the days rTMS was applied lasting up to 3 days after intervention. Depression, anxiety, pain catastrophizing, and affect were unchanged. There was a trend toward improved cognitive function with rTMS compared with sham (P = 0.057). These data indicate that repeated left DLPFC rTMS reduces the pain severity in a model of prolonged muscle pain. The findings may have implications for the development of sustained pain in clinical populations

Experimental muscle hyperalgesia modulates sensorimotor cortical excitability, which is partially altered by unaccustomed exercise

Impaired corticomotor function is reported in patients with lateral epicondylalgia, but the causal link to pain or musculotendinous overloading is unclear. In this study, sensorimotor cortical changes were investigated using a model of persistent pain combined with an overloading condition. In 24 healthy subjects, the effect of nerve growth factor (NGF)-induced pain, combined with delayed-onset muscle soreness (DOMS), was examined on pain perception, pressure pain sensitivity, maximal force, and sensorimotor cortical excitability. Two groups (NGF alone and NGF + DOMS) received injections of NGF into the extensor carpi radialis brevis (ECRB) muscle at day 0, day 2, and day 4. At day 4, the NGF + DOMS group undertook wrist eccentric exercise to induce DOMS in the ECRB muscle. Muscle soreness scores, pressure pain thresholds over the ECRB muscle, maximal grip force, transcranial magnetic stimulation mapping of the cortical ECRB muscle representation, and somatosensory-evoked potentials from radial nerve stimulation were recorded at day 0, day 4, and day 6. Compared with day 0, day 4 showed in both groups: (1) increased muscle soreness (P < 0.01); (2) reduced pressure pain thresholds (P < 0.01); (3) increased motor map volume (P < 0.01); and (4) decreased frontal N30 somatosensory-evoked potential. At day 6, compared with day 4, only the DOMS + NGF group showed: (1) increased muscle soreness score (P < 0.01); (2) decreased grip force (P < 0.01); and (3) decreased motor map volume (P < 0.05). The NGF group did not show any difference on the remaining outcomes from day 4 to day 6. These data suggest that sustained muscle pain modulates sensorimotor cortical excitability and that exercise-induced DOMS alters pain-related corticomotor adaptation

High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain

Based on reciprocal connections between the dorsolateral prefrontal cortex (DLPFC) and basal-ganglia regions associated with sensorimotor cortical excitability, it was hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC would modulate sensorimotor cortical excitability induced by muscle pain. Muscle pain was provoked by injections of nerve growth factor (end of Day-0 and Day-2) into the right extensor carpi radialis brevis (ECRB) muscle in two groups of 15 healthy participants receiving 5 daily sessions (Day-0 to Day-4) of active or sham rTMS. Muscle pain scores and pressure pain thresholds (PPTs) were collected (Day-0, Day-3, Day-5). Assessment of motor cortical excitability using TMS (mapping cortical ECRB muscle representation) and somatosensory evoked potentials (SEPs) from electrical stimulation of the right radial nerve were recorded at Day-0 and Day-5. At Day-0 versus Day-5, the sham compared to active group showed: Higher muscle pain scores and reduced PPTs (P < 0.04); decreased frontal N30 SEP (P < 0.01); increased TMS map volume (P < 0.03). These results indicate that muscle pain exerts modulatory effects on the sensorimotor cortical excitability and left DLPFC rTMS has analgesic effects and modulates pain-induced sensorimotor cortical adaptations. These findings suggest an important role of prefrontal to basal-ganglia function in sensorimotor cortical excitability and pain processing

Safety and feasibility of transcranial direct current stimulation (tDCS) combined with sensorimotor retraining in chronic low back pain: a protocol for a pilot randomised controlled trial

Introduction Chronic low back pain (LBP) is a common and costly health problem yet current treatments demonstrate at best, small effects. The concurrent application of treatments with synergistic clinical and mechanistic effects may improve outcomes in chronic LBP. This pilot trial aims to (1) determine the feasibility, safety and perceived patient response to a combined transcranial direct current stimulation (tDCS) and sensorimotor retraining intervention in chronic LBP and (2) provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. Methods and analysis A pilot randomised, assessor and participant-blind, sham-controlled trial will be conducted. Eighty participants with chronic LBP will be randomly allocated to receive either (1) active tDCS + sensorimotor retraining or (2) sham tDCS + sensorimotor retraining. tDCS (active or sham) will be applied to the primary motor cortex for 20 min immediately prior to 60 min of supervised sensorimotor retraining twice per week for 10 weeks. Participants in both groups will complete home exercises three times per week. Feasibility, safety, pain, disability and pain system function will be assessed immediately before and after the 10-week intervention. Analysis of feasibility and safety will be performed using descriptive statistics. Statistical analyses will be conducted based on intention-to-treat and per protocol and will be used to determine trends for effectiveness. Ethics and dissemination Ethical approval has been gained from the institutional human research ethics committee (H10184). Written informed consent will be provided by all participants. Results from this pilot study will be submitted for publication in peer-reviewed journals. Trial registration number ACTRN1261600062448

Movement does not promote recovery of motor output following acute experimental muscle pain

Objective. To examine the effect of motor activity on the magnitude and duration of altered corticomotor output following experimental muscle pain. Design. Experimental, pre-post test. Setting. University laboratory. Subjects. Twenty healthy individuals. Methods. Participants were randomly allocated to a Rest or Movement group. The Rest group sat quietly without moving for the duration of the experiment. The Movement group repeated a unimanual pattern of five sequential keystrokes as quickly and as accurately as possible immediately following the resolution of pain. Pain was induced into the right extensor carpi radialis brevis muscle by a bolus injection of 0.5 mL hypertonic saline. Corticomotor output was assessed as motor evoked potentials in response to transcranial magnetic stimulation before, immediately after, and at 10, 20, and 30 minutes following pain resolution. Pain intensity was recorded every 30 seconds using an 11-point numerical rating scale. Results. There was no difference in peak pain intensity (P < 0.09) or duration (P < 0.2) between groups. Corticomotor output was reduced in both groups (P < 0.002) at 10 minutes (P < 0.002), 20 minutes (P < 0.02), and 30 minutes (P < 0.037) following the resolution of pain relative to baseline. There was no difference between groups at any time point. Conclusions. Performance of motor activity immediately following the resolution of acute muscle pain did not alter the magnitude or duration of corticomotor depression. Understanding corticomotor depression in the postpain period and what factors promote recovery has relevance for clinical pain syndromes where ongoing motor dysfunction, in the absence of pain, may predispose to symptom persistence or recurrence