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

Peripheral nerve damage often results in the development of chronic pain st ates, resistant to classical analgesics. Since vasoactive intestinal polype ptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are up-regulated in dorsal root ganglion cells following peripheral nerve i njury, we investigated the expression and influence of VPAC(1), VPAC(2) and PAC(1) receptors in rat spinal dorsal horn following a chronic constrictio n injury (CCI). Electrophysiological studies revealed that selective antago nists of VPAC(1), VPAC(2) and PAC(1) receptors inhibit mustard oil-, but no t 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 VP AC(2) receptor antagonists. Ionophoresis of selective agonists for the rece ptor subtypes revealed that the VPAC(2) receptor agonist excited twice as m any cells in CCI compared to normal animals, while the number of cells exci ted by the VPAC(1) receptor agonist decreased and responses to PACAP-38 rem ained unchanged. In situ hybridisation histochemistry (ISHH) confirmed an i ncrease in the expression of VPAC(2) receptor mRNA within the ipsilateral d orsal horn following neuropathy, while VPAC(1) receptor mRNA was seen to de crease and that for PAC(1) receptors remained unchanged. These data indicat e that VIP/PACAP receptors may be important regulatory factors in neuropath ic pain states. (C) 1999 Elsevier Science Ltd. All rights reserved.