Bladder overactivity and afferent hyperexcitability induced by prostate‐to‐bladder cross‐sensitization in rats with prostatic inflammation

Key points

There is clinical evidence showing that prostatic inflammation contributes to overactive bladder symptoms in male patients; however, little is known about the underlying mechanisms. In this study, we investigated the mechanism that prostatic inflammation causes detrusor overactivity by using a rat model of chemically induced prostatic inflammation. We observed a significant number of dorsal root ganglion neurons with dichotomized afferents innervating both prostate and bladder. We also found that prostatic inflammation induces bladder overactivity and urothelial NGF overexpression in the bladder, which are dependent on activation of the pelvic nerve, as well as changes in ion channel expression and hyperexcitability of bladder afferent neurons. These results indicate that the prostate‐to‐bladder cross‐sensitization through primary afferent pathways in the pelvic nerve, which contain dichotomized afferents, would be an important mechanism contributing to bladder overactivity and afferent hyperexcitability induced by prostatic inflammation.

Abstract

Prostatic inflammation is reportedly an important factor inducing lower urinary tract symptoms (LUTS) including urinary frequency, urgency and incontinence in patients with benign prostatic hyperplasia (BPH). However, the underlying mechanisms inducing bladder dysfunction after prostatic inflammation are not well clarified. We therefore investigated the effects of prostatic inflammation on bladder activity and afferent function using a rat model of non‐bacterial prostatic inflammation. We here demonstrated that bladder overactivity, evident as decreased voided volume and shorter intercontraction intervals in cystometry, was observed in rats with prostatic inflammation versus controls. Tissue inflammation, evident as increased myeloperoxidase activity, IL‐1α, IL‐1β, and IL‐6 levels inside the prostate, but not in the bladder, induced an increase NGF expression in the bladder urothelium, which depended on activation of the pelvic nerve, in rats with prostatic inflammation. A significant proportion (18‐19%) of dorsal root ganglion neurons was double labelled by dye tracers injected to either bladder or prostate. In rats with prostatic inflammation, TRPV1, TRPA1 and P2 × 2 were increased, Kv1.4, a potassium channel α‐subunit that can form A‐type potassium (K_A) channels, was decreased at mRNA levels in bladder afferent and double‐labelled neurons vs. non‐labelled neurons, and slow K_A current density was decreased in association with hyperexcitability of these neurons. Collectively, non‐bacterial inflammation localized in the prostate induces bladder overactivity and enhances bladder afferent function. Thus, prostate‐to‐bladder afferent cross‐sensitization through primary afferents in the pelvic nerve, which contain dichotomized afferents, could underlie storage LUTS in symptomatic BPH with prostatic inflammation.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://bit.ly/2AWbNca
via IFTTT