Sympathetic Modulation of Acute Cutaneous Flare Induced by Intradermal Injection of Capsaicin in Anesthetized Rats

Abstract

Much of the acute cutaneous neurogenic inflammation after intradermal injection of capsaicin (CAP) in rats is mediated by dorsal root reflexes (DRRs), which cause the release of inflammatory agents from primary afferent terminals. Sympathetic efferents modulate neurogenic inflammation by interaction with primary afferent terminals. In this study, we examined if DRR-mediated flare after CAP injection is subject to sympathetic modulation. Changes in cutaneous blood flow on the plantar surface of the foot were measured using a laser Doppler flow meter. After CAP injection, cutaneous flare spread more than 20 mm away from the site of CAP injection. However, this CAP-induced flare was significantly reduced after surgical sympathectomy. Decentralization of postganglionic neurons did not affect the flare induced by CAP injection. If the foot of sympathectomized rats was pretreated with an α1-adrenoceptor agonist (phenylephrine) by intra-arterial injection, the spread of flare induced by CAP injection could be restored. However, if the spinal cord was pretreated with a GABAA receptor antagonist, bicuculline, to prevent DRRs, phenylephrine no longer restored the CAP-evoked flare. An α2-adrenoceptor agonist (UK14,304) did not affect the CAP-evoked flare in sympathectomized rats. In sympathetically intact rats, blockade of peripheral α1-adrenoceptors with terazosin profoundly reduced the flare induced by CAP injection, whereas blockade of peripheral α2-adrenoceptors by yohimbine did not obviously affect the flare. Therefore the pathogenesis of acute neurogenic inflammation in the intradermal CAP injection model depends in part on intact sympathetic efferents and α1-adrenoceptors. Peripheral α1-adrenoceptors thus modulate the ability of capsaicin sensitive afferents to evoke the release of inflammatory agents from primary afferents by DRRs.