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 altered when pain is sustained beyond a transient event are scarce. Here, we investigated motor adaptation, and its relationship to corticomotor excitability, in the transition to sustained muscle pain. Twenty-eight healthy individuals were injected with nerve growth factor (NGF) into the right extensor carpi radialis brevis (ECRB) muscle on Days 0 and 2. Motor adaptation and corticomotor excitability were assessed on Day -2, prior to injection on Days 0 and 2, and again on Days 4 and 14. Motor adaptation was quantified during a radial-ulnar movement as kinematic variability of wrist flexion-extension and pronation-supination, and as electromyographic (EMG) variability of ECRB activity. Pain, muscle soreness, and functional limitation were assessed from Days 0-14. Pain, muscle soreness and functional limitation were evident at Days 2 and 4 (p<0.001). EMG 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 while others a decrease. Individuals who displayed an increase in EMG variability following four 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.