Interstitial cystitis (IC) is a chronic inflammatory bladder disease syndrome characterized by urinary frequency, urgency, suprapubic and pelvic pain. Although the etiology and pathogenesis of IC are unknown numerous theories including; infection, autoimmune disorder, toxic urinary agents, deficiency in bladder will lining and neurogenic causes have been proposed. The working hypothesis for this research proposal is that one component of IC involves an alteration of visceral sensation/bladder sensory physiology. Altered visceral sensations from the urinary bladder that accompany IC may be mediated by at least three factors: (1) changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli, (2) changes in the properties of afferent receptors within the urinary bladder induced by inflammatory changes in the target organ and the subsequent awakening of normally """"""""silent"""""""" C-fiber bladder afferents and (3) changes ina the central organization or central synaptic connections of micturition reflex pathways. Thus, I propose that chronic bladder irritation/inflammation induces plastic changes in peripheral bladder afferent pathways as well as reorganization in spinal micturition circuitry. This work tests several hypothesis; (1) the region of the sacral parasympathetic nucleus, essential for coordinated lower urinary tract reflexes, is composed of a number of neuronal subpopulations whose organization is not static but can be altered after chronic bladder irritation (2) the processing of bladder afferent information in specific populations of spinal neurons can be altered after chronic bladder irritation. (3) nitric oxide in the L6-S1 spinal cord or dorsal root ganglia plays a role in the micturition reflex pathways following chronic bladder irritation. (4) changes in the processing of bladder afferent information in the spinal cord following chronic bladder irritation, (4) changes in the processing of bladder afferent information in the spinal cord following chronic bladder irritation are mediated by normally """"""""silent"""""""" C-fiber afferents that are sensitized by chemical mediators released at sites of inflammation in the urinary bladder and (5) electrophysiological and chemical plasticity in bladder afferent neurons can be induced following chronic bladder irritation by neurotrophic factors released in the target organ. A large number of clinical disorders resulting from diseases or injuries to the central nervous system involve autonomic mechanisms in one form or another. Thus, it is very important for the future treatment of many human illnesses that more detailed information be obtained about athe organization of central autonomic pathways. This is particularly true with regard to the neural control of the lower urinary tract in which in impairment of the function of this system is a rather common occurrence due either to neural injury neurological disorders or disease. The diagnosis and treatment of these problems would no doubt be facilitated by a better understanding of the mechanisms controlling the activities of the lower urinary tract.
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