Interstitial cystitis/painful bladder syndrome (IC/PBS) has been suggested to be a local manifestation of asystemic chronic inflammatory disease or condition. Studies have shown that as many as 50% of IC/PBSpatients have irritable bowel syndrome (IBS) whereas a similar high prevalence of IC/PBS presents in IBSpatients. Animal studies have demonstrated that induction of colonic inflammation could cause sensoryneurons in the bladder to release neuropeptides, leading to neurogenic bladder inflammation. However,despite these observations, the impact of co-presence of IBS on IC/PBS remains unclear. Based on clinicaland animal studies, we hypothesize that both localized IC/PBS and IC/PBS with IBS could exhibit similarurological dysfunctions and pain symptoms; however, they are distinctive in pathophysiology, which can bedistinguished by immunological analysis at the molecular and cellular levels. To test this hypothesis, we willconduct the following three specific aims:
Specific Aim 1) To establish a cystitis model with concomitantbowel inflammation, and determine the impact of bowel inflammation on local cystitis;
Specific Aim 2) Todetermine the impact of bowel inflammation on bladder response to intravesical therapeutic agents, and todevelop effective therapy for cystitis with bowel inflammation;
Specific Aim 3) To establish the inflammatoryand gene expression profiles for localized IC/PBS and IC/PBS with IBS, and determine the impact ofconcomitant IBS on bladder expression of inflammatory/neuroinflammatory substances. We will cross ournewly developed URO-OVA mice (a novel bladder inflammation model) with Fabpl-OVA mice (anenterocolitis model) to generate a new cystitis model with concomitant bowel inflammation. We will then useboth URO-OVA mice and the crossed URO/Fabpl-OVA mice (i.e. localized cystitis vs. cystitis with bowelinflammation) to mimic human IC/PBS and IC/PBS with IBS to fulfill our study goals in animal models. Wewill also analyze human biological specimens to establish inflammatory and gene expression profiles forIC/PBS both with and without IBS. Key factors will be identified and new biomarkers will be explored.Successful completion of this study will improve our understanding of the differential immunopathologybetween localized IC/PBS and IC/PBS with bowel inflammation, provide a useful systemic IC/PBS model,and aid future development of new diagnosis and treatment for IC/PBS patients.
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