A high-speed optical imaging technique was employed for visualizing neuronal excitation propagation elicited by afferent stimulation in the mouse trigeminal caudalis (Vc) to clarify the central nociceptive modulation mechanism. Membrane depolarization evoked by a single-pulse stimulation to the spinal trigeminal tract (Tr) was propagated rostrally to the Vc, which was suppressed by CNQX. This is consistent with our morphological observation that axons expand from the Tr into the Vc. A trained-pulse (tetanus) stimulation to the Tr evoked a broad, persistent excitation in the Vc, while MK-801 suppressed it. Neonatally capsaicin-treated mice maintained a single-pulse response but a lacked tetanus-evoked one. These indicated that prolonged depolarization elicited by repetitive stimulation is a prerequisite to C-fiber excitation for activating the NMDA receptors.