The role of VIP/PACAP receptor subtypes in spinal somatosensory processing in rats with an experimental peripheral mononeuropathy

Peripheral nerve damage often results in the development of chronic pain states, resistant to classical analgesics. Since vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are up-regulated in dorsal root ganglion cells following peripheral nerve injury, we investigated the expression and influence of VPAC(1), VPAC(2) and PAC(1) receptors in rat spinal dorsal horn following a chronic constriction injury (CCI). Electrophysiological studies revealed that selective antagonists of VPAC(1), VPAC(2) and PAC(1) receptors inhibit mustard oil-, but not brush-induced activity of dorsal horn neurones in CCI animals, while cold-induced neuronal activity was attenuated by VPAC(1) and PAC(1), but not VPAC(2) receptor antagonists. Ionophoresis of selective agonists for the receptor subtypes revealed that the VPAC(2) receptor agonist excited twice as many cells in CCI compared to normal animals, while the number of cells excited by the VPAC(1) receptor agonist decreased and responses to PACAP-38 remained unchanged. In situ hybridisation histochemistry (ISHH) confirmed an increase in the expression of VPAC(2) receptor mRNA within the ipsilateral dorsal horn following neuropathy, while VPAC(1) receptor mRNA was seen to decrease and that for PAC(1) receptors remained unchanged. These data indicate that VIP/PACAP receptors may be important regulatory factors in neuropathic pain states. (C) 1999 Elsevier Science Ltd. All rights reserved.