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.

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.

Cellular heat stress can cause damage, and significant changes, to a variety of cellular structures. When exposed to chronically high temperatures, yeast cells invaginate vacuolar membranes. In this study, we found that the expression of Atg8, an essential autophagy factor, is induced after chronic heat stress. In addition, without Atg8, vacuolar invaginations are induced conspicuously, beginning earlier and invaginating vacuoles more frequently after heat stress. Our results indicate that Atg8’s invagination-suppressing functions do not require Atg8 lipidation, in contrast with autophagy, which requires Atg8 lipidation. Genetic analyses of vps24 and vps23 further suggest that full ESCRT machinery is necessary to form vacuolar invaginations irrespective of Atg8. In contrast, through a combined mutation with the vacuole BAR domain protein Ivy1, vacuoles show constitutively enhanced invaginated structures. Finally, we found that the atg8Δivy1Δ mutant is sensitive against agents targeting functions of the vacuole and/or plasma membrane (cell wall). Collectively, our findings revealed that Atg8 maintains vacuolar membrane homeostasis in an autophagy-independent function by coordinating with other cellular factors.

The mechanism by which extracellular molecules control serotonergic cell fate remains elusive. Recently, we showed that noggin, which inactivates bone morphogenetic proteins (BMPs), induces serotonergic differentiation of mouse embryonic (ES) and induced pluripotent stem cells with coordinated Address correspondence and reprint requests to Dr Hitoshi Hashimoto, Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: hasimoto@phs.osaka-u.ac.jp 1 These authors contributed equally to this work. Abbreviations used: 5-HT, 5-hydroxytryptamine/serotonin; AcGFP, Aequorea coerulescens green fluorescent protein; BMP, bone morphogenetic protein; ePet, enhancer of the mouse Pet-1 (Fev) gene; ES, embryonic stem; FBS, fetal bovine serum; FGF, fibroblast growth factor; GLuc, Gaussia luciferase; Id, inhibitor of differentiation; iPS, induced pluripotent stem; MAP2, microtubule-associated protein 2; MEM, minimum essential medium; Sert, serotonin transporter; Shh, sonic hedgehog; TGF-b, transforming growth factor-b; Tph2, tryptophan hydroxylase 2; TuJ1, mouse monoclonal anti-class III-tubulin antibody.

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.