Role of TRPA1 & TRPV1 in pain and voiding symptoms in a new mouse CP/CPPS model

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DESCRIPTION (provided by applicant): Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects as many as 16% of men and has enormous quality of life and economic consequences. Currently, there is a dearth of treatment options to manage the pain and voiding symptoms that typically accompany this disease. The development of effective therapies can be greatly facilitated by the development and deployment of small animal models that recapitulate key pathological features of human CP/CPPS. We have recently developed a transgenic mouse CP/CPPS model based on inducible expression of the pro- inflammatory cytokine IL-1ss in the prostate gland. These mice develop chronic prostatitis that can be regulated by administration of Doxycycline in the drinking water, and show clear evidence of inflammatory pain and changes in micturition pattern. The overarching goal of the work proposed here is to dissect the molecular basis of the inflammatory pain and voiding symptoms to inform new therapeutic strategies to treat this disease. We propose to determine the roles played by two Transient Receptor Potential channels (TRP), TRPA1 and TRPV1, in mediating physiological responses to prostatic inflammation. Both TRPA1 and TRPV1 are activated by agents produced in inflammatory environments, and mediate inflammatory symptoms in other tissues. We will approach this problem from a multidisciplinary perspective, bringing together the expertise of a mouse developmental geneticist who specializes in developing mouse models of prostate disease, and a mouse sensory neurophysiologist who specializes in the function of TRP channels. The successful completion of the proposed work will determine whether TRPA1 and/or TRPV1 are viable therapeutic targets to treat human CP/CPPS symptoms, and will provide a new paradigm to dissect the role of any gene in the etiology or progression of this disease.