The sensory neuro-immune interface in osteoarthritis

Abstract The poor correlation between structural damage and pain severity in osteoarthritis remains a major clinical paradox, suggesting that purely structural or inflammatory explanations are insufficient. In this review, we propose the Pain Convergence Model, a hypothesis-generating framework in which biomechanical stress, cellular senescence, and metabolic inflammation converge at the neuro-immune interface to amplify pain signals. This model supports three therapeutic strategies: targeting systemic pathological drivers, modulating the neuro-immune interface, and addressing central sensitization. Translating this framework into clinical practice will require validated biomarkers for patient stratification and mechanism-oriented trial designs, although the model currently awaits experimental validation.