Chronic pelvic pain and prostate inflammation in rat experimental autoimmune prostatitis: Effect of a single treatment with phosphodiesterase 5 inhibitors on chronic pelvic pain.

Abstract

Experimental autoimmune prostatitis (EAP) is most often used as a nonbacterial model of chronic prostatitis/chronic pelvic pain. We investigated the development of chronic pelvic pain and inflammatory changes in rat EAP and examined the effect of a single treatment with phosphodiesterase 5 (PDE5) inhibitors on the chronic pelvic pain. EAP was induced in rats by intradermal injection of rat prostate antigen and complete Freund's adjuvant on days 0 and 28. On day 42, after antigen injection, prostatic inflammatory changes, including the mRNA and protein levels of cytokines/chemokines, were measured and histological analysis of the prostate was performed. Pelvic pain was measured by applying von Frey filaments to the lower abdomen. To confirm that this model is appropriate for evaluating pelvic pain, we tested two drugs, celecoxib and pregabalin, which are clinically used for the treatment of prostatitis-related pain. Subsequently, we examined the effects of single treatments with three phosphodiesterase 5 inhibitors, including tadalafil, on pelvic pain in this model. On day 42, after antigen injection, the mRNA levels of 44 of 84 kinds of cytokines/chemokines and their receptors increased significantly in EAP rats, as did the protein levels of seven of 23 kinds of cytokines/chemokines. Histological analysis revealed inflammation characterized by neutrophils and/or mononuclear cells in the glandular and stromal tissue of the ventral prostate from rats in the EAP group. Some animals in this group showed fibrosis and hemorrhage in the stromal tissue. Pelvic pain had developed in EAP rats, which was attenuated by a single treatment with celecoxib or pregabalin, suggesting that EAP is an appropriate model for prostatitis-related pain. A single treatment with any of the three PDE5 inhibitors tested attenuated the chronic pelvic pain. Prostatitis leads to inflammatory changes in the prostate, which may contribute to the development and maintenance of chronic pelvic pain. PDE5 inhibitors, including tadalafil, may have the ability to block chronic pelvic pain.