Expression and localization of endothelin receptors: Implications for the involvement of peripheral glia in nociception

The endothelins (ETs) are peptides that have a diverse array of functions m ediated by two receptor subtypes, the endothelin A receptor (ETAR) and the endothelin B receptor (ETBR). Pharmacological studies have suggested that i n peripheral tissues, ETAR expression may play a role in signaling acute or neuropathic pain, whereas ETBR expression may be involved in the transmiss ion of chronic inflammatory pain. To begin to define the mechanisms by whic h ET can drive nociceptive signaling, autoradiography and immunohistochemis try were used to examine the distribution of ETAR and ETBR in dorsal root g anglia (DRG) and peripheral nerve of the rat, rabbit, and monkey. In DRG an d peripheral nerve, ETAR-immunoreactivity was present in a subset of small- sized peptidergic and nonpeptidergic sensory neurons and their axons and to a lesser extent in a subset of medium-sized sensory neurons. However, ETBR -immunoreactivity was not seen in DRG neurons or axons but rather in DRG sa tellite cells and nonmyelinating ensheathing Schwann cells. Thus, when ETs are released in peripheral tissues, they could act directly on ETAR-express ing sensory neurons and on ETBR-expressing DRG satellite cells or nonmyelin ating Schwann cells. These data indicate that ETs can have direct, nocicept ive effects on the peripheral sensory nervous system and that peripheral gl ia may be directly involved in signaling nociceptive events in peripheral t issues.