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Title: The role of VIP/PACAP receptor subtypes in spinal somatosensory processing in rats with an experimental peripheral mononeuropathy
Author: Dickinson, T.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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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 VIP1, VIP2 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 VIP1, VIP2 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, VIP1 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 VIP2 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, VIP1 and PACAP receptor antagonists significantly inhibited cold-induced activity, while a VIP2 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 VIP1, VIP2 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 VIP2 receptor agonist doubled, while the percentage of neurones activated by the VIP1 receptor agonist was seen to decrease. The proportion of cells activated by the PACAP receptor agonist remained unchanged.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available