Prostatic Inflammation Triggers Voiding Dysfunction due to Neural Cross-Talk between the Prostate and Bladder

Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) are common in aging men. Prostatic inflammation is a very common histologic feature of the prostate in men with LUTS. To explain this association, inflammation has been postulated to induce hyperplastic growth. It has also been speculated that inflammation may sensitizes pelvic afferents and dorsal root ganglion (DRG) neurons innervating pelvic organs and thereby produce changes in voiding behavior.;The purpose of my work was to test this speculation. We first developed an animal model of E.coli 1677-induced prostatic inflammation without cystitis by nitrofurantoin (NTF) administration. In histology and bacterial culture, it was evident that transurethral instillation of E.coli 1677 caused inflammatory response and infiltration in the prostate but not in the bladder. With our animal model, the effects of prostatic inflammation on voiding behavior were examined by metabolic cage test. We found that the inflamed group showed significantly increased voiding frequency at post-instillation day 1 (PID 1), PID 7 and PID 14 and decreased volume per void at all time points. Linked analysis of voiding frequency and volume per void revealed a preponderance of the low volume and high frequency (LVHF) voiding in mice with prostatic inflammation.;In further studies, we demonstrated an anatomic basis for pelvic cross-talk involving the bladder and prostate by showing (1) shared afferent innervation of the prostate and bladder at spinal segments of T13, L1, L2, L6 and S1 and (2) convergent DRG neurons innervating both prostate and bladder in adult C57BL/6 mice. Taken together, our studies provide the first demonstration that prostatic inflammation induces a change in voiding behavior and provides neuroanatomical evidence to support a postulated mechanism of afferent sensitization and pelvic cross-talk for the association of prostate inflammation and LUTS in aging men.;Our study demonstrates a neural cross-talk between the prostate and bladder and the role of prostatic inflammation on the voiding behavior in adult mouse. Our animal model enables researchers to determine a neuro-peptinergic mechanism critical for inflammation-mediated hyper-sensitization and its contribution on voiding behavior.