To investigate plastic changes in nociceptive sensitivity of the dorsal horn, slow excitatory responses elicited by iteration of high-frequency stimulation were spatiotemporally observed in spinal cord slices of young-adult rats using membrane excitation imaging techniques. Single-pulse stimulation to the dorsal root elicited membrane excitation in lamina II, and high-frequency pulse-train stimulation evoked long-lasting excitation that expanded widely in the dorsal horn. Iteration of high-frequency stimulation enhanced the strength and extent of the excitatory responses, but such augmentation of the excitatory responses disappeared in the presence of an NMDA receptor antagonist (CPP) and was hindered by an NK1 receptor antagonist (L-703.606). The results suggest that activation of both NMDA and NK1 receptors is involved in the enhancement of slow excitatory responses evoked by iteration of high-frequency stimulation. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.