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两种大鼠非细菌性前列腺炎模型的排尿行为和慢性盆腔疼痛:重复给予他达拉非可减轻慢性盆腔疼痛。

Voiding behavior and chronic pelvic pain in two types of rat nonbacterial prostatitis models: Attenuation of chronic pelvic pain by repeated administration of tadalafil.

机构信息

Research Laboratories, Nippon Shinyaku Co., Ltd., Minami-ku, Kyoto, Japan.

出版信息

Prostate. 2019 Apr;79(5):446-453. doi: 10.1002/pros.23750. Epub 2018 Dec 14.

Abstract

BACKGROUND

Experimental autoimmune prostatitis (EAP) and prostatitis induced by 17β-estradiol treatment combined with castration (hormone/castration-induced prostatitis; HCP) are the most commonly used rodent models of nonbacterial prostatitis. We studied the effect of the phosphodiesterase 5 inhibitor tadalafil on chronic pelvic pain in two such models in rats.

METHODS

EAP was induced by intradermal injection of rat prostate antigen and complete Freund's adjuvant on Days 0 and 28. HCP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. On Day 42 after antigen injection in the EAP model and Day 30 after castration in the HCP model, we investigated voiding behavior, pelvic pain (measured by applying von Frey filaments to the lower abdomen), and inflammatory changes, including changes in histopathology and IL-1β, CCL2, and CCL3 mRNA levels. We investigated the effect of repeated administration of tadalafil on chronic pelvic pain in both models.

RESULTS

In the EAP model, we observed inflammation in the ventral prostate, while in the HCP model, we observed inflammation in the lateral lobe of the prostate. Neither model showed any change in voiding behavior. As well as in the EAP model, in which chronic pelvic pain was observed, we found for the first time that HCP led to a significant increase in chronic pelvic pain. Repeated treatment with tadalafil attenuated the chronic pelvic pain in both models.

CONCLUSIONS

Chronic pelvic pain was induced in both EAP and HCP models. Tadalafil significantly attenuated the chronic pelvic pain in both models.

摘要

背景

实验性自身免疫性前列腺炎(EAP)和 17β-雌二醇联合去势治疗引起的前列腺炎(激素/去势诱导的前列腺炎;HCP)是最常用于非细菌性前列腺炎的啮齿动物模型。我们研究了磷酸二酯酶 5 抑制剂他达拉非对两种大鼠模型慢性盆腔疼痛的影响。

方法

EAP 通过在第 0 天和第 28 天皮内注射大鼠前列腺抗原和完全弗氏佐剂诱导。HCP 通过去势后每天皮下注射 17β-雌二醇 30 天诱导。在 EAP 模型中抗原注射后第 42 天和 HCP 模型中去势后第 30 天,我们研究了排尿行为、盆腔疼痛(通过在下腹部应用冯弗雷尔丝测量)和炎症变化,包括组织病理学变化和 IL-1β、CCL2 和 CCL3 mRNA 水平的变化。我们研究了重复给予他达拉非对两种模型慢性盆腔疼痛的影响。

结果

在 EAP 模型中,我们观察到前列腺腹侧有炎症,而在 HCP 模型中,我们观察到前列腺侧叶有炎症。两种模型的排尿行为均无变化。与观察到慢性盆腔疼痛的 EAP 模型一样,我们首次发现 HCP 导致慢性盆腔疼痛显著增加。重复给予他达拉非可减轻两种模型的慢性盆腔疼痛。

结论

EAP 和 HCP 模型均诱导慢性盆腔疼痛。他达拉非显著减轻两种模型的慢性盆腔疼痛。

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