BACKGROUND: Neurotropin (NTP), a biological extract from rabbit skin inoculated with vaccinia virus, is an effective analgesic and anti-allergic agent, and has antipruritic effects in various dermatoses including eczema, dermatitis and urticaria. In patients receiving haemodialysis who have pruritus, NTP appears to exert its antipruritic effect by lowering the plasma levels of substance P (SP), but its underlying mechanisms are not fully understood. AIM: To investigate the antipruritic mechanisms of NTP. METHODS: The effects of NTP on capsaicin-induced SP release from neonatal rat dorsal root ganglion (DRG) neurones were assessed by measuring SP concentrations in culture media by a competitive ELISA. The effects of NTP on nerve growth factor (NGF)-induced neurite outgrowth were assessed by measuring the length of the longest process of cultured DRG neurones. The neuronal cytotoxicity of NTP was determined using a methylthiazole tetrazolium cytotoxicity assay. RESULTS: NTP dose-dependently inhibited capsaicin-induced release of SP from cultured DRG neurones, whereas NTP alone had no effect on SP release. Moreover, NTP dose-dependently inhibited NGF-induced neurite outgrowth in cultured DRG neurones. NTP had no observable cytotoxicity. CONCLUSIONS: These results suggest that NTP exerts its antipruritic effects by inhibiting both SP release and neurite outgrowth of cutaneous sensory nerves.