Experimental muscle pain increases normalized variability of multidirectional forces during isometric contractions

Pain elicits complex adaptations of motor strategy, leading to impairments in the generation and control of steady forces, which depend on muscle architecture. The present study used a cross-over design to assess the effects of muscle pain on the stability of multidirectional (taskrelated and tangential) forces during sustained dorsiflexions, elbow flexions, knee extensions, and plantarflexions. Fifteen healthy subjects performed series of isometric contractions (13-s duration, 2.5, 20, 50, 70% of maximal voluntary force) before, during, and after experimental muscle pain. Three-dimensional force magnitude, angle and variability were measured while the task-related force was provided as feedback to the subjects. Surface electromyography was recorded from agonist and antagonist muscles. Pain was induced in agonist muscles by intramuscular injections of hypertonic (6%) saline with isotonic (0.9%) saline injections as control. The pain intensity was assessed on an electronic visual analogue scale. Experimental muscle pain elicited larger ranges of force angle during knee extensions and plantarflexions (P < 0.03) and higher normalized fluctuations of task-related (P < 0.02) and tangential forces (P < 0.03) compared with control assessments across force levels, while the mean force magnitudes, mean force angle and the level of muscle activity were non-significantly affected by pain. Increased multidirectional force fluctuations probably resulted from multiple mechanisms that, acting together, balanced the mean surface electromyography. Although pain adaptations are believed to aim at the protection of the painful site, the current results show that they result in impairments in steadiness of force

Medial Prefrontal Transcranial Direct Current Stimulation Aimed to Improve Affective and Attentional Modulation of Pain in Chronic Low Back Pain Patients

Chronic low back pain (CLBP) is often without clear underlying pathology. Affective disturbance and dysfunctional pain mechanisms, commonly observed in populations with CLBP, have, therefore, been suggested as potential contributors to CLBP development and maintenance. However, little consensus exists on how these features interact and if they can be targeted using non-invasive brain stimulation. In this pilot trial, 12 participants completed two phases (Active or Sham) of high-definition transcranial direct current stimulation (HD-tDCS) to the medial prefrontal cortex, applied for 20 min on three consecutive days. Clinical pain ratings, questionnaires, and sensitivity to painful cuff pressure were completed at baseline, then 4 trials of conditioned pain modulation (CPM; alone, with distraction using a Flanker task, with positive affect induction, and with negative affect induction using an image slideshow) were performed prior to HD-tDCS on Day 1 and Day 4 (24 h post-HD-tDCS). At baseline, attentional and affective manipulations were effective in inducing the desired state (p p < 0.02) but also showed poor reliability across days. Future work is needed to expand upon these findings and better understand how and if HD-tDCS can be used to enhance attentional and affective effects on pain modulation

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

Angular gyrus connectivity at alpha and beta oscillations is reduced during tonic pain - Differential effect of eye state

The angular gyrus (AG) is a common hub in the pain networks. The role of the AG during pain perception, however, is still unclear. This crossover study examined the effect of tonic pain on resting state functional connectivity (rsFC) of the AG under eyes closed (EC) and eyes open (EO). It included two sessions (placebo/pain) separated by 24 hours. Pain was induced using topical capsaicin (or placebo as control) on the right forearm. Electroencephalographic rsFC assessed by Granger causality was acquired from 28 healthy participants (14 women) before (baseline) and 1-hour following the application of placebo/capsaicin. Subjects were randomly assigned and balanced to groups of recording sequence (EC-EO, EO-EC). Decreased rsFC at alpha-1 and beta, but not alpha-2, oscillations was found during pain compared to baseline during EC only. For alpha-1, EC-EO group showed a pain-induced decrease only among connections between the right AG and each of the posterior cingulate cortex (PCC, P = 0.002), medial prefrontal cortex (mPFC, P = 0.005), and the left AG (P = 0.023). For beta rsFC, the EC-EO group showed a bilateral decrease in rsFC spanning the connections between the right AG and mPFC (P = 0.015) and between the left AG and each of PCC (P = 0.004) and mPFC (P = 0.026). In contrast, the EO-EC group showed an increase in beta rsFC only among connections between the left AG and each of PCC (P = 0.012) and mPFC (P = 0.036). No significant change in the AG rsFC was found during EO. These results provide insight into the involvement of the AG in pain perception and reveal methodological considerations when assessing rsFC during EO and EC