Project Summary/Abstract: The mentee of the application, Dr. Kenny Roman, is a Kirschstein-NRSA postdoctoral fellow in the Department of Urology at Northwestern University. During the award period, Dr. Roman will be provided with laboratory space, animal housing facilities, core labs, equipment, networking opportunities, and crucial mentorship from accomplished faculty to successfully complete the proposed project. Also, the Department of Urology is committed and invested in the future career of Dr. Roman and has offered him a full-time research- track faculty position. Dr. Roman's long term career goals are to 1) to increase his productivity and quality of published basic research, 2) obtain a tenured-track faculty position, and 3) generate significant preliminary data to apply for a competitive RO1 grant. To achieve these goals, Dr. Roman has proposed a career development plan that's designed to provide a balance of mentorship and freedom to help him achieve research independence and self-efficacy. Specifically, the career development plan includes courses to strengthen his knowledge in the field of neuroscience, teach mentorship, and promote his grantsmanship skills. Dr. Roman's mentor (Dr. Praveen Thumbikat) and co-mentors (Dr. Kevin E. McKenna and Dr. Anthony J. Schaeffer) are highly committed to his success and strongly believe in Dr. Roman's potential to establish an independent research program, attain the expertise to obtain R01 funds, and manage a successful academic career. The proposed project will establish a link between activation of the mTOR pathway and changes to neurobiological and neuroinflammatory systems in relevant cortices during the transition from acute to chronic pelvic pain in an autoimmune mouse model of CP/CPPS called experimental autoimmune prostatitis (EAP). Recent studies published by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network showed that the insular cortex is impaired in patients with CP/CPPS. Moreover, preliminary data from the mentee's laboratory suggests the phosphorylation of S6K, a downstream mTOR pathway signaling kinase, is elevated in the prelimbic cortex (interconnected to the insula) of mice with EAP. However, the intracellular signaling mechanisms and cell types that influence changes in specific cortices during the transition from acute to chronic pelvic pain have not been fully explored. Therefore, the long term goal of this project is to identify the mTOR pathway as a signaling mechanism that mediates the transition from acute to chronic pelvic in brain cortices due to neuro-glia interactions in mice with EAP. Overall, the mentee seeks to 1) determine the transition from acute to chronic pelvic pain in mice with EAP, 2) establish the role of the mTOR pathway in driving the transition from acute to chronic pelvic pain in insular and prelimbic cortices, and 3) explore the contribution of neuroinflammation during the transition from acute to chronic pelvic pain in the insular and prelimbic cortices. Successful completion of the research aims will lead to improved treatment options and expand our understanding of the mechanisms that initiate and maintain symptoms associated with CP/CPPS.

Project Narrative: Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) develop debilitating chronic suprapubic pain that impacts the quality-of-life. The proposed project will investigate the mechanistic role of the mTOR pathway in brain cortices during the transition from acute to chronic pelvic pain in a mouse model of CP/CPPS. Thus, the main goal of the proposed project is to expand our understanding of chronic pelvic pain pathogenesis and identify new therapeutic targets in overlooked regions of the brain that are relevant to CP/CPPS.