The role of DAMPS in painful bladder syndrome

DESCRIPTION (provided by applicant): Bladder pain syndrome (BPS or interstitial cystitis, IC) patients typically exhibit marked tenderness of pelvic floor musculature and that treatments directed solely at those muscles often resulted in marked improvement of bladder symptoms. This debilitating syndrome of unknown etiology is often postulated, but not proven, to be associated with microbial infection. To better understand the mechanisms that contribute to BPS/IC, we will study an animal model in which pelvic floor muscle injury alone (somatic injury) the degree to which damage- associated molecular patterns (DAMPs) signal through neuronal receptors that recognize pathogen-associated molecular patterns (PAMPs). A potential neurobiological mechanism for the behavioral changes observed with this injury model is the increased nociceptive signaling present in bladder-associated sensory ganglia. To this end, validation of our injury paradigm in the rodent as an experimental representation of BPS/IC provides us with a number of parameters with which to test potential mediators of somatic and visceral hypersensitivity. Furthermore, the outcomes of these proposed experiments may also provide potential therapeutic targets. Taken together, the use of a clinically-relevant animal model will provide us with the unique opportunity to improve PBS/IC diagnostic and treatment paradigms and increase the understanding of the mechanisms underlying the development and maintenance of chronic pelvic pain conditions in women.