An investigation into the mechanism of capsaicin‐induced oedema in rabbit skin

Abstract

Oedema formation induced by intradermal capsaicin has been studied in rabbit skin. The effect of the anti‐inflammatory steroid dexamethasone and also of a range of known inhibitors of oedema formation have been investigated in order to elucidate mechanisms involved in capsaicin‐induced oedema formation. Oedema formation, in response to intradermally‐injected test agents, was measured by the local extravascular accumulation of intravenously injected 125I‐labelled albumin. In separate experiments skin blood flow was assessed by the clearance of intradermally‐injected 133xenon. Oedema formation induced by intradermal histamine (3 nmol) and bradykinin (1 nmol), when in the presence of vasodilator doses of calcitonin gene‐related peptide (CGRP) (3 pmol) or prostaglandin E1, (PGE1) (10 pmol), was significantly inhibited (P < 0.01) in rabbits pretreated with intravenous dexamethasone (3 mg kg−1, −4h). In contrast dexamethasone had no effect on capsaicin (3 μmol)‐induced oedema formation or, on capsaicin (30–100 nmol)‐induced blood flow. Oedema formation observed in response to intradermal capsaicin (3 μmol) was significantly inhibited (P < 0.01) when the selective capsaicin antagonist, ruthenium red (3 nmol) was co‐injected. This suggests that the mechanism of capsaicin‐induced oedema involves activation of sensory nerves. However, oedema was not inhibited when capsaicin was co‐injected with the neurokinin NK1 receptor antagonist, RP67580 (10 nmol), the NK2 antagonist SR48960 (10 nmol) or the CGRP antagonist CGRP8–37 (300 pmol). Oedema formation induced by capsaicin was not inhibited when co‐injected with the histamine H1 receptor antagonist, mepyramine (3 nmol), the PAF antagonist, WEB 2086 (100 nmol), the bradykinin B2 receptor antagonist, Hoe140 (1 nmol), or the cyclo‐oxygenase inhibitor, indomethacin (10 nmol), suggesting that these mediators do not play a major role in the capsaicin‐induced response. Histological analysis of capsaicin‐treated skin sites revealed undamaged, intact microvessels and lack of haemorrhage. Further, co‐injection of capsaicin with the hydrogen peroxide remover, catalase (2,200 u), had no effect on oedema formation. This suggests that capsaicin does not induce oedema formation secondary to free radical‐induced damage. These results indicate that capsaicin‐induced oedema in rabbit skin involves activation of sensory nerves. However, the oedema is not inhibited by pretreatment with the anti‐inflammatory steroid, dexamethasone. Further the mechanisms which lead to the oedema formation observed after intradermal capsaicin remain unknown. 1995 British Pharmacological Society