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

Aspectos metodológicos de los modelos de prostatitis crónica inducida químicamente/síndrome de dolor pélvico crónico: una revisión sistemática

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., λ-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 Sprague-Drawly rats. λ-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 semi-quantitative 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).

Resumen

Antecedentes: La prostatitis crónica/síndrome de dolor pélvico crónico (CP/CPPS) es un trastorno urológico de alta prevalencia, pero poco comprendido, con un éxito limitado de las terapias disponibles. Los modelos de CP/CPPS inducidos químicamente en roedores se han convertido en herramientas valiosas para la elucidación de su etiopatogenia y la evaluación de terapias. Sin embargo, la diversidad metodológica podría limitar su relevancia translacional. El objetivo de esta revisión sistemática fue evaluar diferentes aspectos metodológicos de los modelos de CP/CPPS inducidos químicamente en roedores. Métodos: Se realizó una búsqueda sistemática en PubMed y Scopus (desde el año 2000 hasta el 13 de junio de 2025), de acuerdo con las directrices Elementos de informe preferidos para revisiones sistemáticas y metanálisis (PRISMA). Se incluyeron los estudios que incluían modelos in vivo de CP/CPPS inducidos por agentes químicos (p.ej., λ-carragenina, adyuvante completo de Freund). Los datos clave extraídos incluyeron especie y cepa, tipo y dosis de agente químico, diseño del grupo control, evaluaciones morfológicas y del dolor, e intervenciones terapéuticas. Resultados: Cincuenta y seis estudios cumplieron con los criterios de inclusión. Se utilizaron ratas con mayor frecuencia que ratones, con predominio de ratas Sprague-Drawly. La λ-carragenina fue el agente químico más utilizado para inducir CP/CPPS (en el 62.5% de los estudios). No se realizaron evaluaciones del comportamiento relacionado con el dolor en más de la mitad de los estudios incluidos (57%), mientras que la hiperalgesia mecánica se evaluó con mayor frecuencia que la hiperalgesia térmica. La validación morfológica se realizó en el 84% de los estudios, principalmente mediante tinción con hematoxilina y eosina y puntuación semicuantitativa. Las terapias probadas fueron diversas, incluyendo extractos de hierbas (39%), pero los protocolos de intervención variaron considerablemente. Conclusiones: Los modelos de CP/CPPS inducidos químicamente son valiosos para la investigación traslacional, pero se debe reducir la variabilidad metodológica significativa. Se necesitan protocolos estandarizados para la inducción, la validación y las evaluaciones del tratamiento para mejorar la reproducibilidad y la relevancia clínica de los modelos de CP/CPPS. Registro PROSPERO: El estudio se registró en PROSPERO (CRD420251106861).

Prostate; Animal models; Carrageenan; Complete Freund’s adjuvant; Pain

Palabras Clave

Próstata; Modelos animales; Carragenina; Adyuvante completo de Freund; Dolor

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