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

• Main Author: Dickinson, Tracey
• Published: University of Edinburgh 1998
• Subjects: 616.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649526

Since the expression of Vasoactive Intestinal Polypeptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is markedly up-regulated in dorsal root ganglia following peripheral nerve injury, we investigated whether VIP/PACAP receptors are important regulators of the amplified sensory responses which develop following neuropathy. This study addressed the role of VIP<SUB>1</SUB>, VIP<SUB>2</SUB> and PACAP receptors with regard to the responses of dorsal horn neurones in normal compared to CCI animals, using novel selective agonists and antagonists. In electrophysiological experiments on anaesthetised rats, the effects of ionophoretic application of VIP<SUB>1</SUB>, VIP<SUB>2</SUB> and PACAP receptor antagonists were investigated on neuronal activity induced by innocuous brushing or cold stimulation of the cutaneous receptive field, or following peripheral application of the chemical algogen mustard oil. In normal rats, VIP<SUB>1</SUB> and PACAP receptor antagonists appeared to exert a general modification of dorsal horn neurone responses, inhibiting both brush- and mustard oil-induced activity to similar extents. In contrast, a novel VIP<SUB>2</SUB> receptor antagonist selectively inhibited mustard oil-evoked activity, whilst showing negligible effects on brush-evoked activity. The effects of the VIP/PACAP receptor antagonists changed markedly in CCI animals, such that antagonists for all three receptor subtypes showed negligible effects on brush-induced activity of dorsal horn neurones. In contrast, VIP<SUB>1</SUB> and PACAP receptor antagonists significantly inhibited cold-induced activity, while a VIP<SUB>2</SUB> receptor antagonist had little effect. However, mustard oil-induced activity was significantly inhibited by all three receptor antagonists in CCI animals. The activity of single, multireceptive dorsal horn neurones was markedly increased following ionophoretic administration of selective VIP<SUB>1</SUB>, VIP<SUB>2</SUB> and PACAP receptor agonists both in normal and CCI rats. Following nerve injury however, two main differences were apparent, and these may reflect changes in receptor expression: the number of dorsal horn neurones activated by the VIP<SUB>2</SUB> receptor agonist doubled, while the percentage of neurones activated by the VIP<SUB>1</SUB> receptor agonist was seen to decrease. The proportion of cells activated by the PACAP receptor agonist remained unchanged.