The actions of capsaicin applied topically to the skin of the rat on C‐fibre afferents, antidromic vasodilatation and substance P levels

Abstract

Single applications of solutions of capsaicin were made to the intact skin of anaesthetized rats and the effects on cutaneous blood flow and the firing of C‐nociceptor afferents determined. Blood flow was measured by laser‐Doppler flowmetry. C‐fibre activity was recorded from filaments dissected from the saphenous nerve. Following the application of a capsaicin solution (concentration ≥ 1 mm) to rat saphenous skin, low frequency firing occurred in C‐polymodal nociceptors that sometimes continued for > 10 min. At the some time, large increases in skin blood flow occurred exceeding 300% in some instances. After the initial excitation, some C‐polymodal nociceptors lost their sensitivity to pressure whilst their sensitivity to heat was lost or enhanced depending on the vehicle used. Sensitivity of C‐polymodal nociceptors to heat recovered in > 1 day following a single application of 33 mm capsaicin. Thresholds to mechanical pressure, however, were still significantly elevated by 123% on day 1, but had recovered on day 2. Vasodilatation in response to saphenous nerve stimulation (‘antidromic vasodilatation’) was significantly reduced by 35%, 2 days after a single application of 33 mm capsaicin, but was normal at 4 days. 6 Following a single application of 33 mm capsaicin, skin substance P levels fell to only half the normal value at day 1 and remained at this level throughout the 4 day period examined. 7 It is suggested that the ability of relatively low concentrations of capsaicin to desensitize C‐fibre nociceptors may underlie the analgesic action of topical capsaicin in man. 1992 British Pharmacological Society