Neurovascular and Behavorial Response to Cystitis

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DESCRIPTION (provided by applicant): Interstitial Cystitis (IC) is a disorder of uncertain etiology that primarily results in increased supra-pubic pain and increased voiding frequency. Although IC often appears to develop in the wake of urinary tract infection (acute or repeated), the acute and chronic effects of urinary tract infection on bladder innervation, vasculature, and function have not been well characterized. Most studies of inflammatory cystitis in animal models have utilized chemically induced models of cystitis and focused on acute effects. There is a critical need to extend observations made on chemically induced cystitis to the effects of bacterial cystitis and to characterize the long-term effects of acute and chronic infectious cystitis. The proposed research will address the hypothesis that repeated urinary tract infection results in persistent changes in bladder innervation, vasculature, and function that contribute to symptoms of IC after the infection is apparently resolved. We will also address the corollary hypotheses that these changes may be mimicked by prolonged chemical cystitis induced by systemic administration of CYP and that susceptibility of mice to the durable the effects of inflammatory cystitis on bladder innervation, vasculature, and function vary among different strains of mice. The proposed research will use an integrated experimental approach and novel imaging techniques to characterize the cellular, histological, neurological, and behavioral response to bladder inflammation (acute and chronic) and determine whether changes persist after removal of the initiating stimulus. This research will investigate the durability of changes that occur in response to a common clinical problem and elucidate the ways in which a "simple UTr' may create a cascade of changes in the bladder physiology and function, neuroregulation, pain perception and behavior that underlie the complex clinical face of IC. The long range plan for this line of research is to link the information generated in the proposed study to future investigations into the genetic basis for variations in susceptibility to cystitis among strains of mice and how this relates to variability among humans regarding sensitivity to the effects of UTI and the occurrence of painful bladder disorders of uncertain etiology, such as IC.