The induction of nerve growth factor (NGF) in inflammatory tissue has been shown to be involved in hyperalgesia. In the present study, the role of neurotrophin-3 (NT-3) in the regulation of inflammatory hyperalgesia was analyzed. Inflammatory hyperalgesia was induced by intraplantar injection of complete Freund's adjuvant (CFA) to the rat hind paw. NT-3 levels in the plantar skin were much higher than NGF levels (1.24 and 0.14 ng/g tissue, respectively) before CFA injection, but decreased significantly 6 h to 48 h after the injection while NGF was markedly induced at 6 h but decreased thereafter. When 1 microg of NT-3 was locally injected at 5 h after CFA injection at the time NT-3 levels decreased, hyperalgesia was reversed transiently but specifically. These results suggest an inhibitory role of NT-3 in the regulation of pain sensitivity.