Presentation Authors: Shinsuke Mizoguchi*, Pittsburgh, PA, Kenichi Mori, Hiromitsu Mimata, Oita, Japan, Jianshu Ni, Masahiro Kurobe, Tetsuichi Saito, Donaldo B. DeFranco, Zhou Wang, Naoki Yoshimura, Pittsburgh, PA
Introduction: There is increasing evidence that prostatic inflammation contributes to lower urinary tract symptoms (LUTS) in male with benign prostatic hyperplasia (BPH) and that cyclooxygenase-2 (COX-2) expression is increased in BPH tissues from patients exhibiting significant inflammation. Therefore, to reveal the role of COX-2-dependent prostatic inflammation in bladder overactivity, we investigated bladder function and molecular expressions in the prostate and pelvic afferent pathways after prostatic inflammation as well as the effects of COX-2 inhibition on bladder overactivity using a rat model.
Methods: Male SD rats at 8 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (Sham). Rats with prostatic inflammation were divided into COX-2 inhibitor (celecoxib) therapy (Treatment) and placebo groups (Placebo). Rats were treated with celecoxib at a dose of 10mg/kg daily from 2 days before induction of prostatic inflammation. Twenty-eight days later, conscious cystometry was performed to assess bladder function. After cystometry, the prostate and L6-S1 dorsal root ganglia (DRG) were excised for analysis of mRNA expression levels of IL1Î² and COX-2 in the prostate and a K+ channel Î±-subunit, Kv1.4, in DRG as well as histological evaluation of prostate and bladder.
Results: In cystometry, intercontraction intervals (ICI) were significantly decreased in Placebo group compared to Sham group. mRNA expressions of IL1Î² and COX-2 in the prostate were significantly increased while mRNA expression of Kv1.4 in L6-S1 DRG was significantly decreased in Placebo group compared to Sham rats. However, these changes were normalized in Treatment group. Prostatic sections from Placebo group demonstrated infiltration of inflammatory cells, but not in Sham or Treatment group. There were no significant inflammatory changes in bladder sections from any groups.
Conclusions: COX-2 inhibition improved not only prostatic inflammation evidenced by decreases of upregulated IL1Î² and COX-2 levels, but also bladder overactivity as shown by shorter ICI in association with decreased Kv1.4 expression in pelvic afferent pathways. These results suggest that prostatic inflammation mediated by COX-2 plays an important role in bladder overactivity possibly induced by prostate-to-bladder cross-talk through pelvic afferent pathways. Thus, these COX-2-dependent mechanisms might contribute to male LUTS due to BPH associated with prostatic inflammation.
Source of Funding: NIH U54DK112079