Recently, it has been proposed that bruxism could represent an overlearned behavior due to the absence of corticomotor plasticity following a relevant tooth-clenching task (TCT). This study assessed the modulatory effects of a nerve growth factor (NGF) injection on masseter muscle corticomotor excitability, jaw motor performance, pain, and limitation in bruxer and control participants following a TCT. Participants characterized as definitive bruxers or controls were randomly assigned to have injected into the right masseter muscle either NGF or isotonic saline (IS), resulting in a study with 4 arms: IS_Control (n = 7), IS_Bruxer (n = 7); NGF_Control (n = 6), and NGF_Bruxer (n = 8). The primary outcome was the masseter motor evoked potential (MEP) amplitude measured at baseline and after a TCT. After the interventions, significantly higher and lower MEP amplitude and corticomotor map area were observed, respectively, in the IS_Control and NGF_Control groups (P < 0.05). Precision and accuracy depended on the series and target force level with significant between-group differences (P < 0.01). NGF-induced masseter muscle sensitization, in combination with a training-induced effect, can significantly impact the corticomotor excitability of the masseter muscle in control participants indicating substantial changes in corticomotor excitability, which are not observed in bruxers. These preliminary findings may have therapeuthic implications for the potential to "detrain" and manage bruxism, but further studies with larger sample sizes will be needed to test this new concept.