Chronic pelvic pain is the hallmark of patients with Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a category of prostatitis that is a significant source of morbidity in American men. A microbial etiology for CP/CPPS has long been postulated but a cause and effect relationship has been difficult to demonstrate due to the chronic nature of the syndrome, the often-delayed diagnosis, and the confounding presence of bacteria in prostates of healthy men. We recently identified a clinical E. coli strain named CP1 from a patient with chronic pelvic pain that was capable of faithfully replicating the chronic pain state in a mouse model of bacterial prostatitis. The CP1 strain infected the prostate of NOD and B6 mice, resulting in an inflammatory response in both strains but inducing the chronic pain state only in NOD mice. Chronic pain persisted even in the absence of detectable bacterial colonization. Our preliminary studies show that the pain is transferable using CD4+ T cells and is associated with a predominant Th1/Th17 immune response. In contrast, CP1 infection in the non-pain permissible B6 mice induced CD4 T cells with an IL-4 response and elevated levels of FoxP3+ CD25+ regulatory T cells. Infection with NU14, a non-pain inducing E. coli strain also resulted in elevated levels of FoxP3+ CD25+ regulatory T cells in both the NOD and B6 mice, suggesting an association between the presence of regulatory T cells and absence of pelvic pain. These studies lead us to hypothesize that bacterial-induced chronic pelvic pain is mediated by IFN-? and IL-17 secreting CD4+ T cells and suppressed by regulatory T cells in the prostate. We will address our hypothesis using the following specific aims: 1. identifying the functional role of Th1/Th17 T cells in chronic pelvic pain. 2. Defining the mechanism of T cell trafficking to the injured prostate. 3. Identifying strategies to promote self-tolerance in the prostate. These studies are expected to result in an understanding of specific mechanisms of chronic pelvic pain in CPPS as well as identification of novel methodologies to effect pain reduction and disease resolution in CPPS patients.

Public Health Relevance

Chronic pelvic pain is the hallmark of patients with chronic pelvic pain syndrome (CPPS), a category of prostatitis that is a significant source of morbidity in American men. The cause of CPPS is unknown and there is an urgent need for understanding the disease mechanism to drive targeted therapy. This project will attempt to define the mechanism behind CPPS and test novel methods to achieve disease resolution.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kirkali, Ziya
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Schools of Medicine
United States
Zip Code
Anker, Jonathan F; Mok, Hanlin; Naseem, Anum F et al. (2018) A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer. J Vis Exp :
Anker, Jonathan F; Naseem, Anum F; Mok, Hanlin et al. (2018) Multi-faceted immunomodulatory and tissue-tropic clinical bacterial isolate potentiates prostate cancer immunotherapy. Nat Commun 9:1591
Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph D et al. (2017) Commensal bacterial modulation of the host immune response to ameliorate pain in a murine model of chronic prostatitis. Pain 158:1517-1527
Roman, Kenny; Murphy, Stephen F; Done, Joseph D et al. (2016) Role of PAR2 in the Development of Lower Urinary Tract Dysfunction. J Urol 196:588-98
Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph et al. (2015) IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP). PLoS One 10:e0125623
Wong, Larry; Done, Joseph D; Schaeffer, Anthony J et al. (2015) Experimental autoimmune prostatitis induces microglial activation in the spinal cord. Prostate 75:50-9
Simons, Brian W; Durham, Nicholas M; Bruno, Tullia C et al. (2015) A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression. J Pathol 235:478-89
Roman, Kenny; Done, Joseph D; Schaeffer, Anthony J et al. (2014) Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome. Pain 155:1328-38
Murphy, Stephen F; Schaeffer, Anthony J; Thumbikat, Praveen (2014) Immune mediators of chronic pelvic pain syndrome. Nat Rev Urol 11:259-69
Quick, Marsha L; Done, Joseph D; Thumbikat, Praveen (2013) Measurement of tactile allodynia in a murine model of bacterial prostatitis. J Vis Exp :e50158

Showing the most recent 10 out of 11 publications