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To determine if short-term (15 min) training in a novel tongue-task is associated with rapid neuroplasticity of the tongue primary motor area (MI) in the human cerebral cortex, and if intra-oral tonic pain affects the tongue MI neuroplasticity and tongue-task training performance. Nine healthy volunteers (7 men, 2 women, mean age 24 ± 1.1 years) participated in two cross-over training sessions in which the application to the tongue of the algesic chemical capsaicin (1%) or vehicle cream was randomized. Prior to and again immediately after 15 min of training in a tongue-protrusion task, transcranial magnetic stimulation (TMS) was applied to the MI in each session and motor evoked potentials (MEPs) were recorded in the tongue musculature and the first dorsal interosseous (FDI) muscle (as control). Neuroplasticity of the tongue MI, as reflected in a significantly enhanced TMS–MEP stimulus–response curve and reduced MEP threshold, was observed after the vehicle session but not after the capsaicin session. Subjects’ overall mean performance scores were significantly higher in the vehicle session than in the capsaicin session. MI neuroplasticity may rapidly occur in association with successful performance in novel tongue-task training, but intra-oral tonic pain interferes with these effects. These findings suggest that nociceptive input modulates MI neuroplasticity associated with novel motor training and may impair the ability to learn a new motor task.