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

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 VPAC1, VPAC2 and PAC1 receptors in rat spinal dorsal horn following a chronic constriction injury (CCI). Electrophysiological studies revealed that selective antagonists of VPAC1, VPAC2 and PAC1 receptors inhibit mustard oil-, but not brush-induced activity of dorsal horn neurones in CCI animals, while cold-induced neuronal activity was attenuated by VPAC1 and PAC1, but not VPAC2 receptor antagonists. Ionophoresis of selective agonists for the receptor subtypes revealed that the VPAC2 receptor agonist excited twice as many cells in CCI compared to normal animals, while the number of cells excited by the VPAC1 receptor agonist decreased and responses to PACAP-38 remained unchanged. In situ hybridisation histochemistry (ISHH) confirmed an increase in the expression of VPAC2 receptor mRNA within the ipsilateral dorsal horn following neuropathy, while VPAC1 receptor mRNA was seen to decrease and that for PAC1 receptors remained unchanged. These data indicate that VIP/PACAP receptors may be important regulatory factors in neuropathic pain states.