Expression of α1-adrenoceptors on peripheral nociceptive neurons

The purpose of this study was to determine whether α(1)-adrenoceptors are expressed on primary nociceptive afferents that innervate healthy skin. Skin and dorsal root ganglia were collected from adult male Wistar rats and assessed using fluorescence immunohistochemistry with antibodies directed against α(1)-adrenoceptors alone or in combination with specific labels including myelin basic protein and neurofilament 200 (markers of myelinated nerve fibres), protein gene product 9.5 (a pan-neuronal marker), tyrosine hydroxylase (sympathetic neurons), isolectin B(4) (IB(4): non-peptidergic sensory neurons), calcitonin gene related peptide (CGRP) and transient receptor potential vanilloid receptor 1 (TRPV1) (peptidergic sensory neurons). Double labelling in dorsal root ganglia confirmed the expression of α(1)-adrenoceptors within sub-populations of CGRP, IB(4) and TRPV1 immunoreactive neurons. Myelinated and unmyelinated sensory nerve fibres in the skin expressed α(1)-adrenoceptors whereas sympathetic nerve fibres did not. The expression of α(1)-adrenoceptors on C- and A-delta nociceptive afferent fibres provides a histochemical substrate for direct excitation of these fibres by adrenergic agonists. This may help to explain the mechanism of sensory-sympathetic coupling that sometimes develops on surviving primary nociceptive afferents in neuropathic pain states.