1178 PROSTATE-TO-BLADDER AFFERENT CROSS-SENSITIZATION AS A MECHANISM INDUCING BLADDER OVERACTIVITY IN PROSTATIC INFLAMMATION

Abstract

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Prostate & Genitalia1 Apr 20131178 PROSTATE-TO-BLADDER AFFERENT CROSS-SENSITIZATION AS A MECHANISM INDUCING BLADDER OVERACTIVITY IN PROSTATIC INFLAMMATION Yasuhito Funahashi, Ryosuke Takahashi, Pradeep Tyagi, Momokazu Gotoh, and Naoki Yoshimura Yasuhito FunahashiYasuhito Funahashi Nagoya, Japan More articles by this author , Ryosuke TakahashiRyosuke Takahashi Pittsburgh, PA More articles by this author , Pradeep TyagiPradeep Tyagi Pittsburgh, PA More articles by this author , Momokazu GotohMomokazu Gotoh Nagoya, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.815AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) often exhibit irritative bladder symptoms despite no evidence of bladder inflammation. We previously reported that afferent cross-sensitization between prostate and bladder is a possible mechanism for this association (2012 AUA). The present study investigated the effects of prostatic inflammation on bladder activity and afferent nerve function using a rat model of nonbacterial prostatitis. METHODS Male SD rats were injected with formalin into the ventral lobes of the prostate. Voiding behavior and conscious cystometry were evaluated after 1 week. Histological analyses (H&E staining, toluidine blue staining, and NGF immunostaining) and ELISA for inflammation-related proteins were performed for the bladder and prostate. Fluorescent dyes (DiI and Fast Blue [FB]) were injected into the prostate and bladder wall, respectively to identify organ-specific afferent neurons. Dye-labeled neurons in S1 dorsal root ganglia (DRG) were dissected using laser-capture microdissection methods, and mRNA levels of TRP receptors and ATP receptors were measured by real-time RT-PCR. Patch-clamp recordings were also performed in capsaicin-sensitive FB- and double-labeled neurons dissociated from L6-S1 DRG. RESULTS Prostatitis rats exhibited bladder overactivity as evidenced by decreased single voided volume (metabolic cage) and intercontraction intervals (cystometry). H&E staining showed inflammation restricted inside the prostate, but not in the bladder. The number of activated mast cells and NGF expression increased in the bladder of prostatitis rats. MPO activity, IL-1α, IL-1β, and IL-6 in the formalin-injected prostate was increased, but not in the bladder. TRPV1, TRPA1 and P2X2 mRNA were increased in DiI, FB and double-labeled neurons compared to non-labeled neurons. Patch-clamp recordings showed hyperexcitability of FB- and double-labeled afferent neurons as evidenced by significant increases in spike firing frequency during membrane depolarization and capsaicin-induced inward currents. CONCLUSIONS Formalin-induced inflammation localized in the prostate induces bladder overactivity associated with increases of bladder mast cell activation and NGF, and enhances functional properties of not only dichotomized afferents, but also bladder afferent neurons. Prostate-to-bladder afferent cross-sensitization through dichotomized afferents following prostatic inflammation is a potential mechanism inducing bladder overactivity in CP/CPPS. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e481 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhito Funahashi Nagoya, Japan More articles by this author Ryosuke Takahashi Pittsburgh, PA More articles by this author Pradeep Tyagi Pittsburgh, PA More articles by this author Momokazu Gotoh Nagoya, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...