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Long‐lasting bladder overactivity and bladder afferent hyperexcitability in rats with chemically‐induced prostatic inflammation
Author(s) -
Ni Jianshu,
Mizoguchi Shinsuke,
Bernardi Kyrie,
Suzuki Takahisa,
Kurobe Masahiro,
Takaoka Eiichiro,
Wang Zhou,
DeFranco Donald B.,
Tyagi Pradeep,
Gu Baojun,
Yoshimura Naoki
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23794
Subject(s) - inflammation , afferent , medicine , prostate , urinary bladder , prostatic diseases , urinary bladder disease , urology , pathology , cancer
Abstract Background Benign prostatic hyperplasia (BPH) is one of the major causes of lower urinary tract symptoms (LUTS), including storage LUTS such as urinary frequency and urgency. Recently, a growing number of clinical studies indicate that prostatic inflammation could be an important pathophysiological mechanism inducing storage LUTS in patients with BPH. Here we aimed to investigate whether nonbacterial prostatic inflammation in a rat model induced by intraprostatic formalin injection can lead to long‐lasting bladder overactivity and changes in bladder afferent neuron excitability. Methods Male Sprague‐Dawley rats were divided into four groups (n = 12 each): normal control group, 1‐week prostatic inflammation group, 4‐week inflammation group, and 8‐week inflammation group. Prostatic inflammation was induced by formalin (10%; 50 µL per lobe) injection into bilateral ventral lobes of the prostate. Voiding behavior was evaluated in metabolic cages for each group. Ventral lobes of the prostate and the bladder were then removed for hematoxylin and eosin (HE) staining to evaluate inflammation levels. Continuous cystometrograms (CMG) were recorded to measure intercontraction intervals (ICI) and voided volume per micturition. Whole‐cell patch clamp recordings were performed on dissociated bladder afferent neurons labeled by fluorogold injected into the bladder wall, to examine the electrophysiological properties. Results Results of metabolic cage measurements showed that formalin‐treated rats exhibited significantly ( P < 0.05) increases in micturition episodes/12 hours and decrease in voided volume per micturition at every time point post injection. Continuous CMG illustrated the significant ( P < 0.05) higher number of nonvoiding contractions per void and shorter ICI in formalin‐treated rats compared with control rats. HE staining showed significant prostatic inflammation, which declined gradually, in prostate tissues of formalin‐induced rats. In patch clamp recordings, capsaicin‐sensitive bladder afferent neurons from rats with prostatic inflammation had significantly ( P < 0.05) lower thresholds for spike activation and a “multiple” firing pattern compared with control rats at every time point post injection. Conclusions Formalin‐induced prostatic inflammation can lead to long‐lasting bladder overactivity in association with bladder afferent neuron hyperexcitability. This long‐lasting model could be a useful tool for the study of inflammation‐related aspects of male LUTS pathophysiology.