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Repetitive movements (RM) are a main risk factor for musculoskeletal pain, which is partly explained by the overloading of musculoskeletal structures. However, RM may also drive brain plasticity, leading to maladaptive changes in sensorimotor areas and altered pain processing. This study aimed to understand whether individuals performing extensive RM (musicians) exhibit altered brain processing to prolonged experimental muscle pain. Nineteen healthy musicians and 20 healthy non-trained controls attended three sessions (Day1-Day3-Day8). In each session, event-related potentials (ERPs) to non-nociceptive superficial and nociceptive intra-epidermal electrical stimulation, reaction times (RTs), electrical detection thresholds (EDTs), and pressure pain thresholds (PPTs) were recorded. In all participants, prolonged muscle pain was induced by intramuscular injection of nerve growth factor (NGF) into the right first dorsal interosseous muscle at the end of Day1. Pain intensity was assessed on a numerical rating scale (NRS) and was lower in musicians compared to non-musicians (p<0.007). Compared with Day1, NGF reduced PPTs on Day3-Day8 (p<0.001) and non-nociceptive P200 and P300 ERP amplitudes on Day8 (p<0.044) in both groups. Musicians compared to controls showed secondary hyperalgesia to electrical stimulation on Day3-Day8 (p<0.004) and reduced nociceptive P200 ERP amplitudes on Day8 (p<0.005). Across participants, ERP components correlated with pain detection (RTs), sensitivity (PPTs and EDTs), and severity (NRS), (all p<0.043). In musicians, the amount of weekly training was associated with higher NGF-induced NRS pain scores on Day3-Day8 (p<0.037). These results show that repetitive sensorimotor training leads to brain changes in the processing of prolonged pain, biasing the cortical response to nociceptive inputs.