Musculoskeletal pain is associated with altered motor control that, despite short-term benefit, is hypothesised to have long-term consequences, contributing to the development of chronic pain. However, data on how motor control is alteredwhen pain is sustained beyond a transient event are scarce. Here, we investigated motor adaptation, and its relationship with corticomotor excitability, in the transition to sustainedmuscle pain. Twenty-eight healthy individuals were injected with nerve growth factor into the right extensor carpi radialis brevis muscle on days 0 and 2. Motor adaptation and corticomotor excitability were assessed on day 22, before injection on days 0 and 2, and again on days 4 and 14.Motor adaptation was quantified during a radial-ulnarmovement as kinematic variability of wrist flexion-extension and pronation-supination, and as electromyographic (EMG) variability of extensor carpi radialis brevis activity. Pain,muscle soreness, and functional limitationwere assessed fromdays 0 to 14. Pain, muscle soreness, and functional limitation were evident at days 2 and 4 (P < 0.001). Electromyographic variability reduced at days 4 and 14 (P < 0.04), with no change in kinematic variability (P = 0.9). However, data revealed variation in EMG and kinematic variability between individuals: some displayed increased motor variability,whereas others a decrease. Individualswho displayed an increase in EMGvariability after 4 days of pain also displayed an increase in corticomotor excitability (r = 0.43, P = 0.034). These findings suggest individual adaptation of the motor system in the transition to sustained pain that could have implications for clinical musculoskeletal pain disorders.