Several recent studies with transcranial magnetic stimulation (TMS) have demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs, but little is known about the regulation of the human tongue motor control. To test the effect of local anesthesia (LA) of the lingual nerve and topical application of capsaicin stimulation on tongue MEPs. Fourteen volunteers participated (21-30 years) in two randomized sessions; before, during a nerve block of the lingual nerve or topical capsaicin application (30 microl 5%) on the tongue, and after anesthesia or pain had subsided. EMG electrodes were placed on the tongue and the first dorsal interosseous (FDI) muscle (control). EMG signals were amplified, filtered (20 Hz-1 kHz), and sampled at 4 kHz (Nicolet, USA). TMS were delivered with a figure-of-eight coil (Magstim 200, UK). Scalp sites at which EMG responses were evoked in the relaxed tongue or FDI at the lowest stimulus strength were determined, i.e., motor threshold (T). MEPs were assessed using stimulus-response curves in steps of 10% T. Eight stimuli were presented at each stimulus level. The proximal hypoglossal nerve was activated by TMS delivered over the parieto-occipital skull distal to the right ear. Eight stimuli were delivered at 50% of maximum stimulator output. ANOVAs were used to analyze latency and peak-to-peak amplitudes. Capsaicin evoked mild pain (2.8+/-0.5), and a strong burning sensation (6.2+/-0.4) on 0-10 visual analogue scales. MEP amplitudes in tongue and FDI were not influenced by capsaicin (P>0.44) but by stimulus strength (P<0.001). MEP latencies in tongue (8.9+/-0.2 ms) and FDI (22.4+/-0.4 ms) were not affected by capsaicin (P>0.19). Hypoglossal nerve stimulation evoked a short-latency (3.6+/-0.9 ms) response (mean amplitude 65+/-9 microV); but was unaffected by capsaicin (P>0.54). LA did not have any effect on FDI MEPs but was associated with a significant facilitation of tongue MEPs at T+50% and T+60% about 50 min after the nerve block in the recovery phase. Also in this condition, the direct motor responses evoked by hypoglossal nerve stimulation remained constant. No direct effect of a strong burning sensation could be shown on peripheral or central corticomotor pathways to the relaxed tongue musculature, however, LA of the lingual nerve (cranial nerve V) seems able to induce a delayed change in corticomotor control of tongue musculature (cranial nerve XII) possibly related to unmasking effects at the cortical level but not completely excluding excitability changes at the brain stem level.