ANIMAL MODEL OF INTERSTITIAL CYSTITIS

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The overall goal of this proposal is to establish Feline Urologic Syndrome (FUS) in female cats as a model of Interstitial Cystitis (IC) in humans. To accomplish this goal, we will study cats with naturally-occurring FUS belonging to clients, and cats maintained in our research cattery. Interstitial cystitis is a painful, debilitating disease that usually afflicts women. A significant impediment to progress in understanding of the causes of IC is the lack of a naturally-occurring animal model of the disease. Female cats with FUS meet nearly all the objective criteria for diagnosis of lC. Moreover, signs of FUS appear to wax and wane more than the symptoms of IC do, a feature that can be exploited by examining cats both when they are showing signs and when they "go into remission" to determine which palimeters are present when the animal appears normal. It is hypothesized that sensory neurons and/or mast cells (MC) play a significant role in FUS and IC, but bladder distention prior to biopsy sample collection inhibits Substance P (SP) and MC identification by inducing release of histamine from MC and SP from sensory neurons. Also, decreased glycosaminoglycan (GAG) excretion and increased bladder permeability are present in cats with FUS. These abnormalities also have been found in women, permitting use of cats to examine their role in the pathogenesis of IC. This three year proposal has four major objectives: (1) To establish the diagnosis of FUS in female cats by NIDDK IC criteria, and to compare these with data collected from normal female cats, and cats with non-FUS urinary tract disease. All cats will be re-examined if signs of FUS recur, or at one year if they do not. Based on previous studies, we expect a one-year recurrence rate of approximately 50%. These animals will not be evaluated more frequently to avoid potential therapeutic effects of repeated bladder distention on the disease process. (2) To examine the effect of distention on SP and MC in bladder wall. (3) To determine the effects of FUS on glycosaminoglycan excretion in urine. (4) To determine the effects of FUS on bladder permeability using 99mTcDTPA. The use of both client-owned and research cats is an important aspect of these investigations because they will allow us to study a naturally occurring disease model of lC.