Methodological aspects of chemically-induced chronic prostatitis/chronic pelvic pain syndrome models: a systematic review

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent but poorly understood urological disorder with limited success of available therapies. Chemically induced rodent models of CP/CPPS have become valuable tools for elucidation of its ethiopathogenesis and evaluation of therapies. However, methodological diversity could limit translational relevance. The aim of this systematic review was to assess different methodological aspects of chemically induced CP/CPPS models in rodents. Methods: A systematic search was conducted in PubMed and Scopus (2000 up to 13 June 2025), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they involved in vivo models of CP/CPPS induced by chemical agents (e.g., lambda carrageenan, complete Freund's adjuvant). Key data extracted included species and strain, chemical agent type and dose, control group design, pain and morphological assessments and therapeutic interventions. Results: Fifty-six studies met our inclusion criteria. Rats were more frequently used than mice, with the domination of SpragueDrawly rats. lambda-carrageenan was the most frequently used chemical agent to induce CP/CPPS (in 62.5% of studies). Pain-related behavior assessments were not done in more than a half of included studies (57%), while mechanical hyperalgesia was assessed more frequently than thermal hyperalgesia. Morphological validation was done in 84% of studies, primarily using hematoxylin and eosin staining and semiquantitative scoring. Therapies tested were diverse, including herbal extracts (39%), but intervention protocols varied widely. Conclusions: Chemically induced CP/CPPS models are valuable for translational research, but significant methodological variability should be ameliorated. Standardized protocols for induction, validation, and treatment assessments are needed to enhance reproducibility and clinical relevance of CP/CPPS models. The PROSPERO Registration: The study was registered at PROSPERO (CRD420251106861).