Capsaicin (Cap) is a pharmacological tool to inactivate nociceptive afferents. The present study was undertaken to investigate the effects of topical application of Cap to sciatic nerve on the formalin-induced expression of proto-oncogene proteins c-fos in the rat spinal cord using immunohistochemical display of fos-like protein. In rats subjected to formalin injection into the hind paw, numerous fos-like immunoreactivity (FLI) neurons were found in the spinal dorsal horn, with heavy labeling in laminae I-II and V-VI. Following pretreatment of Cap, formalin-induced FLI expression was significantly abolished. It was suggested that activation of Cap-sensitive unmyelinated nociceptive afferents following formalin injection was primarily responsible for the activation of c-fos gene. Our data also provided further evidence supporting that topical application was an effective way to block the transmission of noxious primary afferents.