Metabolic syndrome and osteoarthritis pain: common molecular mechanisms and potential therapeutic implications.

There is no clear evidence from epidemiological and animal studies of a direct link between metabolic syndrome (MetS) and cartilage degeneration in osteoarthritis (OA) once body mass index (BMI) has been considered. However, recent epidemiological studies indicate a significant role for MetS in predicting increased knee pain after adjustment for BMI. This implies there are mechanisms that underlie both MetS and OA pain. In addition to the common systemic inflammatory and pro-inflammatory components of the two disorders, there are other molecular mechanisms that may link MetS and OA pain. These include regulation of the endocannabinoid system, activation of the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1) channel and gut dysbiosis. These three mechanisms are interlinked and are the target of therapeutic dietary or pharmacological interventions. Exploring and understanding these mechanisms may help improve outcomes for both pain and metabolic comorbidities affecting individuals with OA.