Sympathetic Modulation of Activity in A - and C-Primary Nociceptive Afferents After Intradermal Injection of Capsaicin in Rats

Ren, Yong, Xiaoju Zou, Li Fang, and Qing Lin. Sympathetic modulation of activity in A and C-primary nociceptive afferents after intradermal injection of capsaicin in rats. J Neurophysiol 93: 365–377, 2005. First published September 15, 2004; doi:10.1152/ jn.00804.2004. Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of A and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some A and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 l) injection, but the enhanced responses of both A and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an 1adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of A -fibers. In contrast, a blockade of 2-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of A and C-primary afferent fibers to mechanical stimuli and that 1-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.