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.

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.

10Hz repetitive transcranial magnetic stimulation (10Hz-rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) produces analgesia, probably by activating the pain modulation system. A newer rTMS paradigm, called theta burst stimulation (TBS), has been developed. Unlike 10Hz-rTMS, prolonged continuous TBS (pcTBS) mimics endogenous theta rhythms, which can improve induction of synaptic long-term potentiation. Therefore, this study investigated whether pcTBS to the L-DLPFC reduced pain sensitivity more efficiently compared with 10Hz-rTMS, the analgesic effects lasted beyond the stimulation period, and the reduced pain sensitivity was associated with increased efficacy of conditioned pain modulation (CPM) and/or intra-cortical excitability. Sixteen subjects participated in a randomized cross-over study with pcTBS and 10Hz-rTMS. Pain thresholds to heat (HPT), cold (CPT), pressure (PPT), intra-cortical excitability assessment, and CPM with mechanical and heat supra-pain threshold test stimuli and the cold pressor test as conditioning were collected before (Baseline), 3 (Day3) and 4 days (Day4) after 3-day session of rTMS. HPTs and PPTs increased with 10Hz-rTMS and pcTBS at Day3 and Day4 compared with Baseline (P=0.007).Based on pooled data from pcTBS and 10Hz-rTMS, the increased PPTs correlated with increased efficacy of CPM at Day3 (P=0.008), while no correlations were found at Day4 or with the intracortical excitability.Perspective: Preliminary results of this comparative study did not show stronger pain sensitivity reduction by pcTBS compared with 10Hz-rTMS to the L-DPFC. Both protocols maintained increased pain thresholds up to 24-hours after the last session, which were partially associated with modulation of CPM efficacy but not with the intra-cortical excitability changes.

2019) High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain. NeuroImage,

Changes in excitability of the sensorimotor cortex have been demonstrated in clinical musculoskeletal pain, although the timing is unknown. Eccentric exercise provokes delayed-onset muscle soreness providing a model to study the temporal profile of sensorimotor cortical plasticity during progressively developing muscle soreness. Twelve healthy participants performed eccentric exercise of the wrist extensors. Likert pain scores, pressure pain thresholds at the extensor carpi radialis (ECR) muscle, somatosensory evoked potentials from electrical stimulation of the radial nerve, maximal wrist extension force, and ECR motor evoked potentials to transcranial magnetic stimulation were recorded before (baseline) and at 2 hours (2-h post), 2 days (day 2), and 6 days (day 6) after exercise. Compared with baseline, 1) the Likert pain score was increased at 2-h post and increased further at day 2 (P < .01); 2) the ECR pressure pain thresholds were decreased at day 2 (P < .001); 3) the P45 amplitude of the somatosensory evoked potential from central-parietal recording sites was increased at day 2 (P < .001); 4) maximal wrist extension force was reduced 2-h post and at day 2 (P < .002); and 5) the cortical area from which ECR motor evoked potentials could be elicited was reduced at 2-h post and at day 2 (P < .03). A decrease in the ECR pressure pain thresholds was correlated (P < .027) with an increase in the P45 amplitude at a centroparietal recording site. PERSPECTIVE: These novel data demonstrate that the somatosensory cortical excitability may be affected by muscle soreness developing over days in parallel with a deficit in the motor system. Cortical neuroplasticity may thus develop in the subacute phase and be relevant for understanding neural adaptation in the transition from acute to persistent pain.

Gravitational unloading leads to adaptations of the human body, including the spine and its adjacent structures, making it more vulnerable to injury and pain. The Functional Re‐adaptive Exercise Device (FRED) has been developed to activate the deep spinal muscles, lumbar multifidus (LM) and transversus abdominis (TrA), that provide inter‐segmental control and spinal protection. The FRED provides an unstable base of support and combines weight bearing in up‐right posture with side alternating, elliptical leg movements, without any resistance to movement. The present study investigated the activation of LM, TrA, obliquus externus (OE), obliquus internus (OI), abdominis, and erector spinae (ES) during FRED exercise using intramuscular fine‐wire and surface EMG. Nine healthy male volunteers (27 ± 5 years) have been recruited for the study. FRED exercise was compared with treadmill walking. It was confirmed that LM and TrA were continually active during FRED exercise. Compared with walking, FRED exercise resulted in similar mean activation of LM and TrA, less activation of OE, OI, ES, and greater variability of lumbo‐pelvic muscle activation patterns between individual FRED/gait cycles. These data suggest that FRED continuously engages LM and TrA, and therefore, has the potential as a stationary exercise device to train these muscles.

Exposure to axial unloading induces adaptations in paraspinal muscles, as shown after spaceflights. This study investigated whether daily exposure to artificial gravity (AG) mitigated lumbar spine flattening and muscle atrophy associated with 60-day head-down tilt (HDT) bed rest (Earth-based space analogue). Twenty-four healthy individuals participated in the study: Eight received 30 minutes continuous AG; eight received 6x5 minutes AG, interspersed with rest periods; eight received no AG exposure (control group). Magnetic Resonance Imaging (MRI) of the lumbopelvic region was conducted at baseline (BDC) and at day 59 of HDT (HDT59). T1-weighted images were used to assess morphology of the lumbar spine (spinal length, intervertebral disc angles, disc area) and volumes of the lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 vertebral levels. A chemical shift-based 2‐point lipid/water Dixon sequence was used to evaluate muscle composition. Results showed that: spinal length and disc area increased (P<0.05); intervertebral disc angles (P<0.05) and muscle volumes of LM, LES, and QL reduced (P<0.01); and fat/water ratio for the LM and LES muscles increased (P<0.01) after HDT59 in all groups. Neither of the AG protocols mitigated the lumbar spinal deconditioning induced by HDT bed rest. The increase in lipid/water ratio in LM and LES muscles indicates an increased relative intramuscular lipid concentration. Altered muscle composition in atrophied muscles may impair lumbar spine function after body unloading, which could increase injury risk to vulnerable soft tissues. This relationship needs further investigation.

This study investigated whether artificial gravity (AG), induced by short-radius centrifugation, mitigated deterioration in standing balance and anticipatory postural adjustments (APAs) of trunk muscles following 60-day head-down tilt bed rest. Twenty-four participants were allocated to one of three groups: control group (N=8); 30 minutes continuous AG daily (N=8); intermittent 6x5 minutes AG daily (N=8). Before and immediately after bed rest, standing balance was assessed in four conditions: eyes open and closed on both stable and foam surfaces. Measures including sway path, root-mean-square, and peak sway velocity, sway area, sway frequency power, and sway density curve were extracted from the centre of pressure displacement. APAs were assessed during rapid arm movements using intramuscular or surface electromyography electrodes of the rectus abdominis, obliquus externus and internus abdominis, transversus abdominis, erector spinae at L1, L2, L3, and L4 vertebral levels, and deep lumbar multifidus muscles. The relative latency between the EMG onset of the deltoid and each of the trunk muscles was calculated. All three groups had poorer balance performance in most of the parameters (all P<0.05) and delayed APAs of the trunk muscles following bed rest (all P<0.05). Sway path and sway velocity were deteriorated, and sway frequency power was less in those who received intermittent AG than in the control group (all P<0.05), particularly in conditions with reduced proprioceptive feedback. These data highlight the potential of intermittent AG to mitigate deterioration of some aspects of postural control induced by gravitational unloading, but no protective effects on trunk muscle responses were observed.