DPT+BCG co-administration establishes robust C57BL/6N mouse model for chronic prostatitis pain and inflammation

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition affecting many young and middle-aged men, characterized by persistent pelvic pain and urinary symptoms without bacterial infection. Despite its prevalence, existing animal models often fail to fully capture the complex inflammatory and neuropathic features of human CP/CPPS, limiting mechanistic studies and the development of effective therapies. A robust and reproducible animal model is crucial for dissecting the underlying pathophysiology, identifying novel therapeutic targets, and testing preclinical hypotheses for this challenging syndrome.

Researchers established a CP/CPPS model in C57BL/6N mice by immunizing them with prostate antigen (PAg) plus complete Freund's adjuvant (CFA). Mice were divided into groups receiving DPT, BCG, or DPT+BCG as booster immunizations. The study assessed pain-related phenotypes using Von Frey testing, measured cytokine levels via ELISA, analyzed immune cell populations with flow cytometry, and evaluated prostate pathology through HE staining and immunohistochemistry. This comprehensive approach aimed to characterize the inflammatory and pain responses induced by different immunization strategies.

Booster immunization with PAg+CFA+DPT+BCG induced the strongest pain-related phenotype compared to the NC (normal control) group. This combined approach significantly increased levels of pro-inflammatory cytokines IL-1β and TNF-α, while simultaneously reducing the anti-inflammatory cytokine IL-10. Histopathological analysis revealed aggravated prostatic inflammation in the DPT+BCG group. Furthermore, this group exhibited increased expression of key inflammatory mediators including NLRP3, COX-2, NF-κB, and Caspase-1 within the prostate tissue. These findings indicate a robust inflammatory cascade and pain sensitization.

Compared with either DPT or BCG monotherapy, the PAg+CFA+DPT+BCG group consistently demonstrated stronger inflammatory and pain-related phenotypes across most measured readouts, highlighting the synergistic effect of the co-administration.