Presenting Author:

Kenny Roman, Ph.D.

Principal Investigator:

Praveen Thumbikat, DVM

Department:

Urology

Keywords:

Prostatitis, chronic, pain, bacteria, E.coli, dorsal root ganglia, neural, urology,

Location:

Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital

B183 - Basic Science

Peripheral Neural Pathways in Murine Models of Bacterial Prostatitis

Background: Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) suffer from chronic pelvic pain and urinary symptoms. The National Institute of Health (NIH) reported a significant impact on the quality of life of CP/CPPS patients with chronic symptoms due to few viable therapeutic targets. Previous data revealed that a prostate uropathogenic Escherichia coli (UPEC) obtained from a CP/CPPS patient (named CP1) can establish chronic pelvic pain in NOD mice. Surprisingly, NOD mice showed sustained pelvic pain after bacterial clearance. Also, behavioral assays showed that the induction of pelvic pain due to CP1 is absent in C57BL/6J mice. Therefore, we seek to expand on our previous findings by examining the unique role of CP1 in activating neural pathways that modulate pelvic pain and micturition. Methods: Male C57BL/6J (B6) and NOD (2-3 months old) mice received intraurethral instillation of CP1 (2X10^10; 10 µl) to elicit chronic pelvic pain. Behavioral pain testing for pelvic allodynia was conducted at days 0, 7, 14, 20, and 30. Fluoro-gold (5% in PBS) was intraurethrally administered (5 µl) at day 20. The bladder, prostate, and dorsal root ganglia (DRG) were excised from mice with CP1 and respective control cohorts at day 30. The bladder, prostate, and DRG, were processed for immunofluorescence. Results: Our behavioral measurements verified that CP1 infected NOD mice develop pelvic pain at day 7 thru day 30. However, B6 mice with CP1 do not develop increased tactile pelvic allodynia compared to control cohorts at day 30. Our immunofluorescence showed that the tracer entered the dorsolateral lobe of the prostate without labeling the bladder. DRG from NOD mice with CP1 showed increased labeling of neurons compared to control cohorts. In contrast, the DRG from B6 with CP1 showed minimal tracer uptake and demonstrated no change to control. Conclusions: This study determined that 1) intraurethral instillation of fluoro-gold tracer can be used to label the dorsolateral prostate, 2) CP1 in genitourinary tissues of NOD mice is responsible for the emergence of prostate-induced chronic pelvic via activation of DRG in the lumbosacral regions, and 3) B6 mice might be protected against CP1 induced peripheral neuronal activation that causes pelvic pain and aberrant micturition.