Okamoto Ken, Kurita Maki, Yamaguchi Hiroshi, Numakura Yuki, Oka Michiko
Research Laboratories, Nippon Shinyaku Co., Ltd., Minami-ku, Kyoto, Japan.
Prostate. 2018 Jul;78(10):707-713. doi: 10.1002/pros.23514. Epub 2018 Mar 26.
Experimental autoimmune prostatitis (EAP) shares important clinical features with clinical chronic prostatitis/chronic pelvic pain. We investigated the effect of tadalafil on pelvic pain and prostatic inflammation in a rat EAP model.
EAP was induced in rats by intradermal injection of rat prostate antigen and complete Freund's adjuvant on days 0 and 28. Rats were treated with tadalafil (2 mg/kg, p.o.; EAP-tadalafil) or vehicle (EAP-vehicle) once daily from day 0, while sham-operated animals were treated with vehicle only (Sham). Tactile allodynia was measured on days 28, 35, and 42 by applying von Frey filaments to the lower abdomen as an index of pelvic pain. On day 42, the plasma immunoglobulin G (IgG) concentration and the testosterone/estradiol ratio were measured and histopathological analysis of the prostate was performed.
Tactile allodynia in the pelvic region was observed on days 28, 35, and 42 after EAP induction. The tactile allodynia observed on day 42 was significantly reduced by repeated treatment with tadalafil. Plasma IgG concentrations increased after EAP induction but the increase was not changed by tadalafil treatment. Prostate tissues were characterized by epithelial necrosis, infiltration of neutrophils and/or lymphocytes to acini and stroma, and fibrosis, in addition to a high stroma-to-epithelium ratio. Tadalafil treatment significantly suppressed the severity of the lesions.
EAP rats developed pelvic pain, prostatic inflammation and increased plasma IgG concentrations. Tadalafil inhibited the chronic pelvic pain and prostatic inflammation, suggesting that its anti-inflammatory action may contribute to its blocking of pain development in the EAP model.
实验性自身免疫性前列腺炎（EAP）与临床慢性前列腺炎/慢性盆腔疼痛具有重要的临床特征。我们研究了他达拉非对大鼠EAP模型中盆腔疼痛和前列腺炎症的影响。
在第0天和第28天通过皮内注射大鼠前列腺抗原和完全弗氏佐剂诱导大鼠发生EAP。从第0天起，大鼠每天接受一次他达拉非（2 mg/kg，口服；EAP-他达拉非组）或赋形剂（EAP-赋形剂组）治疗，而假手术动物仅接受赋形剂治疗（假手术组）。在第28、35和42天，通过将von Frey细丝应用于下腹部来测量触觉异常性疼痛，作为盆腔疼痛的指标。在第42天，测量血浆免疫球蛋白G（IgG）浓度和睾酮/雌二醇比值，并对前列腺进行组织病理学分析。
在EAP诱导后第28、35和42天观察到盆腔区域的触觉异常性疼痛。他达拉非重复治疗可显著减轻第42天观察到的触觉异常性疼痛。EAP诱导后血浆IgG浓度升高，但他达拉非治疗未改变这种升高。前列腺组织的特征除了高基质与上皮比值外，还有上皮坏死、中性粒细胞和/或淋巴细胞向腺泡和基质浸润以及纤维化。他达拉非治疗显著抑制了病变的严重程度。
EAP大鼠出现盆腔疼痛、前列腺炎症和血浆IgG浓度升高。他达拉非抑制了慢性盆腔疼痛和前列腺炎症，表明其抗炎作用可能有助于其在EAP模型中阻断疼痛的发生。
