Blood flow in the plantar hindpaw skin of anaesthetized ratswas measured by Iaser Doppler flowmetry. Intraplantar injection of interleukin-lß (50 pg) significantly enhanced the hyperaemic response to intraplantar capsaicin (0.3 ,.,.g). Pretreatment with a neurotoxic dose of capsaicin reduced the capsaicin-evoked hyperaemia and prevented the facilitatory effect of interleukin-lß. Blockade of nitric oxide formation by N°-nitro-L-arginine methyl ester failed to affect the capsaicin-evoked vasodilatation but abolished its amplification by interleukin-lß. These data indicate that the enhancement by interleukin-lß of the capsaicin-induced hyperaemia involves thin afferent nerve fibres and depends on nitric mdde as esse'ntial intermediate.
lntroductionThe cutaneous vasodilatation induced by topical administration of capsaicin is to a large extent mediated by activation of thin afferent neiVe fibres and release of vasoactive peptides from their peripheral endings (Holzer, 1992). We have previously shown that the inflammatory cytokine interleukin-lß enhances the hyperaemia evoked by injection of capsaicin into the rat plantar hindpaw skin in a prostaglandin-dependent manner (Herbert and Holzer, 1994). Since the vasodilator effect of calcitonin gene-related peptide (CGRP), the major neuragenie mediator of the capsaicin-induced vasodilatation (Hughes and Brain, 1991;Brain et al., 1993), was not altered by interleukin-1ß it was concluded that the effect of the cytokine was brought about by sensitization of afferent neiVe endings to capsaicin (Herbert and Holzer, 1994).This inference was further tested here by examining the effect of interleukin-1/3 in rats in which thin afferent neurones bad been defunctionalized by systemic