Accelerating recovery of acute musculoskeletal pain using non-invasive brain stimulation : a randomised controlled trial

Background: Maximising recovery and facilitating return to sport following musculoskeletal injury are important goals for athletes and their rehabilitation providers. Non-invasive stimulation of the primary motor cortex using repetitive transcranial magnetic stimulation (rTMS) has recently been shown to promote recovery of musculoskeletal pain. However, rTMS studies have primarily focussed upon chronic pain, and the neurophysiological mechanisms underpinning the success of rTMS are yet to be elucidated. A new pain model, intramuscular injection of nerve growth factor (NGF), offers a clinically relevant model of the transition to sustained pain following acute musculoskeletal injury, facilitating exploration of the effects of rTMS in a controlled environment. Therefore, the purpose of this study was to i) determine whether motor cortex rTMS accelerated recovery of musculoskeletal pain and functional limitation induced via repeated NGF injection and ii) investigate the changes in motor cortical excitability induced by rTMS. Method: Thirty healthy individuals participated in 7 experimental sessions (Days 0, 2, 4, 6, 8, 11, and 14). NGF was injected into the right extensor carpi radialis brevis on Days 0, 2, and 4 to induce progressively developing muscle pain. Active (n = 15, 7 female, 24 [4] years) or sham (n = 15, 7 female, 23 [2] years) excitatory rTMS was delivered for five consecutive days, beginning after the final injection. Clinical outcomes (Patient Related Tennis Elbow Evaluations of pain intensity and functional limitation), pressure pain thresholds, and motor cortical excitability (TMS maps) were recorded each session. Results: The active rTMS group had a faster recovery of pain (p = 0.046) and experienced greater increases in pressure pain thresholds (p = 0.012) when compared to the sham rTMS group. There were no differences between the active and sham groups in terms of functional limitation (p = 0.501). Motor cortical excitability (TMS map volume) decreased in both groups following NGF injection (p = 0.042), but there were no differences in excitability between groups following the rTMS intervention (p = 0.488). Conclusion: This study demonstrated that excitatory rTMS accelerates recovery of musculoskeletal pain induced via repeated NGF injection. There were no differences between groups in terms of motor cortical excitability, suggesting that the analgesic effects of rTMS may be mediated by activation of distant interconnected cortical regions, rather than local changes to the motor cortex. These findings hold important implications for the rehabilitation of individuals following acute musculoskeletal injury