NERVE GROWTH FACTOR AND OROFACIAL NEUROPATHIC PAIN

University Of The Pacific-Stockton, Stockton CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Adapted from the investigator's Abstract): Partial injury to somatosensory nerves in rats results in functional and cytochemical alterations in sensory neurons and in pain-associated behaviors that closely resemble human clinical neuropathic pain states. The long-term objectives of this research are to further clarify the peripheral and central mechanisms that contribute to the development and pathophysiology of neuropathic pain, and to characterize and evaluate the roles of nerve growth factor (NGF), other neurotrophins and sympathetic nerves in these processes. A standard model for trigeminal neuropathic injury in adult rats (unilateral infraorbital nerve constriction) will be used, but the proposed studies offer several unique opportunities. First, an autoimmune model of NGF depletion will be used to investigate the role of NGF in the development of neuropathic pain. Second, each experiment will assess changes in free ranging behavior, behavioral reactions to orofacial stimulation (von Frey stimulation), electrophysiological response properties of trigeminal ganglion neurons (receptive field and fiber type, spontaneous activity, evoked activity and conduction velocity), and ganglionic cytochemistry (CGRP, tyrosine hydroxylase, c-jun, glial fibrillary acidic protein, p75 and trkA NGF receptors and brain derived neurotrophic factor) in the ipsilateral and contralateral sensory neurons and their support cells in the same animal. Third, the somatotopic organization of the trigeminal ganglion is well known, and will allow the discrimination of those effects directly attributable to nerve injury, per se, from those that are centrally mediated, or that result from intraganglionic mechanisms. Finally, clinical studies suggest that lesions of the trigeminal nerve lead to chronic pain conditions that differ from those of segmental nerves (e.g., sciatic), due in part to the anatomical-physiological organization of the trigeminal system. The studies outlined in this proposal will lead to a greater understanding of the behavioral, physiological and cytochemical alterations that occur after trigeminal sensory nerve injury, and as a consequence will have important implications for the clinical management of neuropathic pain in the orofacial region.