Assessing the translational value of animal models in developing pain-targeting therapies for clinical osteoarthritis.

Osteoarthritis (OA) is a highly prevalent and disabling disease, with pain as its most debilitating symptom. Despite extensive preclinical research, no therapy has successfully translated from animal models into routine clinical use. Commonly used animal models (e.g., acute, surgically, or chemically induced OA in young, single-sex animals) often fail to reflect the chronic and multifactorial human condition, which is often seen in older, postmenopausal women with comorbidities and mixed nociceptive-neuropathic pain. This review aims to identify animal models and pain assessment methods for predicting drug efficacy in OA pain management and to examine the translational gap, focusing on pain as a primary endpoint in animal and human clinical studies. Ultimately, we emphasize the need for phenotype-specific, clinically relevant models to improve translational validity and accelerate the development of effective OA pain therapies.