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

Kurita, Maki; Yamaguchi, Hiroshi; Okamoto, Ken; Kotera, Takashi; Oka, Michiko

doi:10.1002/pros.23690

Cited by 18 publications

(19 citation statements)

References 38 publications

(68 reference statements)

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“…Six to eight-week-old male NOD mice were intradermally immunized in different locations: bilateral hint footpads, the lower back, and the base of the tail with PAgs (300 μg/mouse, EAP group) or phosphate buffer solution (control group) emulsified in CFA in a total volume of 150 μL per mouse, as previously described. 24 According to the experimental schedule, 25,26 the mice were immunized at day 0 and day 28 and at last were killed at day 42.…”

Section: Eap Inductionmentioning

confidence: 99%

Effect of alcohol on chronic pelvic pain and prostatic inflammation in a mouse model of experimental autoimmune prostatitis

et al. 2019

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Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent disease of the urogenital system. Alcohol has been reported to be closely related to CP/CPPS. Thus, we intended to verify the role of alcohol in CP/CPPS and determine the underlying mechanism. Methods We induced experimental autoimmune prostatitis (EAP) mouse model by intradermally injecting a mixture of prostate antigens (PAgs) and complete Freund's adjuvant on days 0 and 28. Mice were treated with alcohol (control‐alcohol and EAP‐alcohol groups) or vehicle (control‐vehicle, and EAP‐vehicle groups) from day 32 to 42. Forty‐two days after PAg injection, the pathological appearance of the prostate tissues was evaluated, and histological analyses of the prostate were performed. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. Proinflammatory cytokines were detected by enzyme‐linked immunosorbent assay tests. Then, we explored the effects of the NLRP3 inhibitor MCC950 on chronic pelvic pain and prostatic inflammation in this model. Results Histological analyses showed diffuse inflammation in the stromal tissues that were characterized by severe infiltration of neutrophils and mononuclear cells in mice in the EAP‐alcohol group compared with EAP‐vehicle group. Chronic pain tests showed that the response frequency was significantly increased using a von Frey filament at forces of 0.4, 1.0, and 4.0 g in EAP‐alcohol group compared with EAP‐vehicle (P < .05). The levels of proinflammatory cytokines, including interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, IL‐17, and IL‐1β were all significantly elevated in EAP‐alcohol group compared with the EAP‐vehicle group (P < .05). However, between the control‐alcohol and control‐vehicle groups, chronic pain tests, histological assays, and cytokine determinations showed no differences. Furthermore, our results demonstrated that MCC950 could decrease the expression level of NLRP3 inflammasome–related proteins including NLRP3, ASC, and caspase‐1. The chronic pain tests, histological assays, and cytokine determinations showed that MCC950 could attenuate the chronic pain and prostatic inflammation through the inhibition of the NLRP3 inflammasome. Conclusions This study indicated that alcohol could aggravate the severity of prostatic inflammation in EAP model though activating the NLRP3 inflammasome. Furthermore, the role of MCC950 in inhibiting NLRP3 inflammasome and decreasing IL‐1β secretion to alleviate EAP severity may show that it is a promising therapeutic agent for CP/CPPS.

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Section: Eap Inductionmentioning

confidence: 99%

Effect of alcohol on chronic pelvic pain and prostatic inflammation in a mouse model of experimental autoimmune prostatitis

et al. 2019

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“…Our recent study (Kurita et al) showed that even a single oral dose of tadalafil or other PDE5 inhibitors (sildenafil and vardenafil) inhibited EAP‐induced chronic pelvic pain. However, in the present study, we did not administer tadalafil to the rats on the last day of the experimental schedule, when the rats were sacrificed in both models.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2018

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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.

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“…Few studies have focused on the effect of tadalafil on chronic prostatitis symptoms in patients with CP/CPPS, although PDE5 inhibitors including tadalafil have been reported to suppress prostate inflammation, fibrosis, and hypo-oxygenation in rabbits fed a high fat diet and to suppress pelvic pain by improving inflammatory changes in an experimental autoimmune prostatitis rat model. 13,14,18,19 In clinical practice, Benelli et al 20 reported that tadalafil significantly improved the NIH-CPSI total score, as well as scores for the pain domain, urinary domain, and QOL domain in 14 patients with CP/CPPS, although they found that the Qmax and PVR in UFM did not improve. In particular, the mean NIH-CPSI pain sub-score decreased from 13.7 to 1.6 after 12 weeks of tadalafil administration, and this change is considered to be noteworthy.…”

Section: Discussionmentioning

confidence: 99%

“…12 Several basic studies have reported that tadalafil significantly suppressed pelvic pain and prostatic inflammation in a nonbacterial prostatitis rat model. 13,14 It is of clinical interest to determine whether these old and new drugs, cernitin and tadalafil, respectively, can improve chronic pain or discomfort of the pelvic, perineal, scrotal, or phallic area in patients with CP/CPPS. To the best of our knowledge, no randomized controlled studies have compared the improvement in chronic prostatitis symptoms, such as chronic pelvic pain, in patients treated with one of these medications.…”

Section: Introductionmentioning

confidence: 99%

Comparison of cernitin pollen extract vs tadalafil therapy for refractory chronic prostatitis/chronic pelvic pain syndrome: A randomized, prospective study

Matsukawa

Naito

Funahashi

et al. 2020

Neurourology and Urodynamics

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Aims To compare the efficacy of cernitin pollen extract (cernitin) or tadalafil for treating persistent chronic pelvic pain despite α1‐blocker monotherapy in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and lower urinary tract symptoms (LUTS). Methods A total of 100 patients with refractory CP/CPPS despite ongoing α1‐blocker monotherapy were randomized to receive add‐on therapy with either cernitin (4 capsules/day) or tadalafil (5 mg/d) for 12 weeks. At week 12, changes from baseline in the patients’ CP/CPPS, LUTS, and voiding function, as assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI), the International Prostate Symptom Score (IPSS), and uroflowmetry, respectively, were compared between the groups. Results The final analysis included 42 and 45 patients in the cernitin and tadalafil groups, respectively. Although the NIH‐CPSI total, NIH‐CPSI pain sub‐score, and NIH‐CPSI quality of life sub‐score significantly improved in both groups, the cernitin (vs tadalafil) group showed significantly greater improvements in the NIH‐CPSI total score (−6.8 vs −4.6; P = .02) and NIH‐CPSI pain sub‐score (−4.1 vs −1.5; P < .001). Half (50%) of the patients in the cernitin group showed a reduction greater than 50% in their NIH‐CPSI pain sub‐score; in the tadalafil group, only four patients (8.9%) showed ≥50% improvement (P < .001). In contrast, the improvement in LUTS was significantly superior in the tadalafil group. Conclusion Both cernitin and tadalafil significantly ameliorated chronic pelvic pain in patients with refractory CP/CPPS. The add‐on of cernitin was more effective than tadalafil for pelvic pain and discomfort.

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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: 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.

Cited by 18 publications

References 38 publications

Effect of alcohol on chronic pelvic pain and prostatic inflammation in a mouse model of experimental autoimmune prostatitis

Effect of alcohol on chronic pelvic pain and prostatic inflammation in a mouse model of experimental autoimmune prostatitis

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

Comparison of cernitin pollen extract vs tadalafil therapy for refractory chronic prostatitis/chronic pelvic pain syndrome: A randomized, prospective study

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