This new project proposes to study modifications of the responsiveness of bladder afferent neurons produced by the autonomic nervous system and the consequences of partial denervation upon these effects. The purpose is to examine the possibility that neural trauma in the pelvic region can lead to a neuropathy affecting sensory fibers. The question to be examined: does partial denervation lead to alterations in characteristics of the remaining or regenerated afferents supplying tahe urinary bladder? The study proposes a systematic survey of the range of characteristics of afferent fibers excited by distension of the bladder in order to determine whether a subset of such afferent units are specialized nociceptors. A major impetus for the study comes from the prominence of sensory symptoms in the syndrome of interstitial cystitis and the syndrome's common occurrence in persons who may have suffered traumatic injury of pelvic structures. Bladder afferent unit characteristics will be examined in rats in association with quantitative cystometrograms. Effects of stimulation of autonomic efferent nerves to the bladder and of autonomic chemical mediators (norepinephrine, SP, VIP, neuropeptide gamma, cholinergics, ATP analogues) on such afferent characteristics are to be studied. The effects of partial denervation as a consequence of injury of the hypogastric, pelvic or sympathetic nerves on the autonomic modulation of sense organ characteristics will be evaluated. Such novel information on sense organs of the bladder and modifications in their characteristics under circumstances paralleling clinical conditions should provide important insight into the etiology of interstitial cystitis and that of other possible neuropathic visceral disorders.
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