Direct evidence for an axonal site of action of capsaicin

Local application of capsaicin to the sciatic nerve of rats induced a long-lasting increase in the nociceptive threshold as tested by the hot-plate method, and prevented neurogenic inflammation in the lateral part of the dorsal skin of the rat's paw. Application of capsaicin to the saphenous nerve prevented the neurogenic inflammatory response, induced either by antidromic electrical stimulation of the saphenous nerve or by painting the skin with mustard oil, in the medial part of the dorsal skin of the paw. The functional impairment induced by local capsaicin treatment of saphenous or sciatic nerves was strictly confined to the skin area supplied by the corresponding nerve. It is suggested that local capsaicin treatment of peripheral nerves selectively damages the chemosensitive nerve fibres presumably by depleting their substance P content.