POSSIBLE NEUROPATHIC ORIGIN OF INTERSTITIAL CYSTITIS

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This proposal is aimed at the etiology of a syndrome largely appearing in women, interstitial cystitis (I.C.). The impetus for the study comes from the prominence of sensory symptoms in this syndrome and a predominant occurrence of I.C. in women who may have suffered traumatic injury of pelvic structures by childbearing or pelvic disease. The possibility that neural damage in the pelvic region can lead to an autonomic neuropathy affecting sensory fibers in some way comparable to the somatic syndrome, causalgia, is to be explored. The effects produced by autonomic efferent activity on bladder afferents are to be tested and how partial denervation modifies any effects is to be examined. The issue is whether partial denervation leads to alterations in characteristics of remaining or regenerated afferent neurons supplying the urinary bladder so, that they become excited by autonomic activity and give rise to the signs and symptoms of I.C. The study proposes a systematic survey of the range of characteristics of afferent fibers excited by cystometric physiological distension of the bladder in normal adult rats in order to establish a control group baseline. As part of this survey, it is planned to gather information on whether a subset of such bladder afferent units are specialized for detection of excessive distention. Effects of stimulation of autonomic efferent nerves to the bladder and of autonomic chemical mediators (norepinephrine, Sp, VIP, neuropeptide Y, cholinergics, ATP analogues) on such afferent characteristics will be examined. How partial denervation produced by injury of the hypogastric, pelvic or sympathetic nerves (under sterile surgical conditions) modifies any autonomic modulation of sense, organ characteristics will then be evaluated. Such information on sense organs of the bladder and modifications in their characteristics under circumstances simulating clinical conditions would be a novel contribution and provide important insight into a possible- sensory neuron etiology of I.C. It has the potential of opening new approaches to treatment of this syndrome and that of other visceral disorders of possible neuropathic origin.