Understanding Motor Adaptation in the Transition to Sustained Pain: Protocol for a Longitudinal Experimental Study.

Background: Chronic pain affects over 30% of the global population and remains a major public health issue due to limited treatment efficacy and the need for mechanism-based, personalized approaches. Motor behavior is theorized to play a role in pain persistence through altered movement patterns, muscle recruitment, and proprioception. While motor behavior is linked to chronic pain, empirical evidence on underlying mechanisms, particularly cortical dynamics, remains scarce. Objective: This study aimed to investigate longitudinal changes in cortical sensorimotor excitability and their relationship with maladaptive motor behaviors. Methods: This prospective longitudinal study will follow 150 healthy participants, aged 18-65 years, recruited from the community, experiencing experimentally induced muscle pain across 4 visits (day 0, day +2, day +4, and 5 days after pain resolution). Pain will be induced using intramuscular injections of nerve growth factor into the extensor carpi radialis brevis muscle. The primary outcome is motor variability assessed during multidimensional wrist movement tasks, and quantified using root-mean-square deviation and muscle synergies (derived from electromyographic recordings of 4 forearm muscles). Secondary outcomes include cortical mechanisms (electroencephalographic peak alpha frequency, transcranial magnetic stimulation mapping, short-interval intracortical inhibition, and intracortical facilitation), sensorimotor integration (evoked potential), cognitive control (multisource interference task), and endogenous pain modulation (conditioned pain modulation). Self-report questionnaires will assess pain intensity and disability (Patient-Rated Tennis Elbow Evaluation, McGill Pain Questionnaire-Short Form, and Likert Muscle Soreness Scale) as well as psychological factors such as fear of movement, pain-related beliefs, and coping strategies (Tampa Scale for Kinesiophobia, Pain Beliefs Questionnaire, and Coping Strategies Questionnaire-Revised). This sample size provides 80% power at 5% significance to detect a medium effect size across 23 predictor variables, with Bonferroni correction and 10% loss-to-follow-up allowance. Data will be analyzed using 2-level growth curve modeling to characterize interindividual differences in motor behavior, cortical dynamics, and pain processing trajectories. Results: All study procedures have been approved by the Western University Health Science Research Ethics Board (review reference 2025-125757-103291). Funding was provided by the Canadian Institutes of Health Research under grant number 517783 for the period 2024-2029. Recruitment for the study began in April 2025, and all data collection is expected to be completed by 2028. As of April 2026, we have enrolled 26 participants. Results are expected to be published at the end of 2028. Conclusions: The findings will advance understanding of motor behavior in pain and lay the foundation for personalized therapies, moving beyond current generic treatments that offer limited benefits.