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

• Published in: The Prostate Vol. 79; no. 12; pp. 1439 - 1449
• Main Authors: Zhang, Li‐Gang, Chen, Jing, Meng, Jia‐Lin, Zhang, Yong, Liu, Yi, Zhan, Chang‐Sheng, Chen, Xian‐Guo, Zhang, Li, Liang, Chao‐Zhao
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-09-2019
• Subjects: Alcohol; Alcohols - pharmacology; Animals; Antigens; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Caspase; Chronic pain; Chronic Pain - immunology; chronic prostatitis/chronic pelvic pain syndrome; Cytokines; Cytokines - immunology; Disease Models, Animal; Ethanol - pharmacology; experimental autoimmune prostatitis; Filaments; Freund's adjuvant; Furans - pharmacology; Inflammasomes; Inflammasomes - immunology; Inflammation; Inflammation - immunology; Interferon; Leukocytes (mononuclear); Leukocytes (neutrophilic); Male; Metastases; Mice; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLRP3 inflammasome; Pain; Pelvic Pain - immunology; Prostate; Prostate - drug effects; Prostate - immunology; Prostate - pathology; Prostatitis; Prostatitis - immunology; Prostatitis - pathology; Rats; Rats, Wistar; Sulfonamides - pharmacology; Tumor necrosis factor; Tumor necrosis factor-TNF; alcohol; NLRP3 inflammasome; inflammation; experimental autoimmune prostatitis; chronic prostatitis/chronic pelvic pain syndrome
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.23866

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.