The role of substance P in the axon reflex in the rat

The increase in vascular permeability in small blood vessels of rat skin induced by antidromic stimulation of sensory roots, nerves, or single identified polymodal nociceptive fibres or by intra-arterial injection of Substance P, has been examined by light and electron microscopy. The effects of local application of capsaicin (a Substance P-depleting agent) to both skin and muscle have also been studied. Nerve stimulation and Substance P induce leakage of a venular pattern similar to that caused by known permeability factors. However, capsaicin causes leakage from both venules and capillaries in a pattern more characteristic of direct endothelial injury. It is suggested that neurogenic leakage may be mediated by local liberation of Substance P, but caution is necessary in interpreting experiments involving the use of capsaicin because of its local toxic effects.