The aim of this project is to characterize the chemical and morphological properties of the small sensory ganglion cells that emit thin afferent axons implicated in nociceptive discharge. Emphasis is placed upon understanding 1) those properties of peripheral afferent terminals underlying efferent regulatory function and effector response to injury in peripheral tissues, and 2) the neural mechanisms responsible for prolonged pain of pathological origin. These studies could provide new therapeutic approaches to recovery following injury and control of chronic pain syndromes. The objective is to provide a morphological basis for identifying and defining the heterogeneous subpopulations of putative peripheral 'nociceptor' axon terminals in visceral tissues suitable for flat-mount study and dominated by unmyelinated innervation, cf. tunica vasculosa of testis and mesenteries. Electrophysiologically characterized nociceptive spots will be analyzed for patterns of peptide expression and for a variety of undetermined co-localization factors in axons labeled by lectins (markers for axon membrane glycoconjugates) with emphasis on the purinergic and adrenergic influences implicated in inflammatory processes and pain. The project shifts from description of innervation in different tissues to electron microscopic studies relying heavily on post-embedment immunogold techniques. Experiments aimed at hypotheses concerning axonal sprouting and regulation of peptide expression will be carried out using immunocytochemical and in situ hybridization methods to define and quantify, at the transcriptional and translational level, changes in sensory neurons induced by sympathectomy and different types of nerve lesions, including axotomy, dorsal rhizotomy, constriction neuropathy, and neuroma formation. The axonal-growth specific protein GAP-43, and its mRNA, will serve as a tool for studying axon outgrowth. Emphasis is also placed on the morphological components underlying the contribution of norepinephrine and adenosine to hyperpathias in rat models affected by these substances. Establishing a peripheral mechanism of action can have direct implications for guiding pain therapy.
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