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.
|Effective start/end date||7/11/18 → 6/30/23|
- National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK114395-03)