Unraveling the hidden link between anti-inflammatory drugs and chronic musculoskeletal inflammation in horses

Unravelling the missing link between anti-inflammatory drugs and chronic musculoskeletal inflammation. Musculoskeletal conditions are the main cause of wastage among equine athletes and translate into significant welfare and financial burdens to the equine industry. Chronic inflammation is a key component of equine musculoskeletal diseases leading to degeneration of tendons, ligaments and joints. Among such conditions, osteoarthritis (OA) is overrepresented (~60%). In such a scenario, the use of anti-inflammatory drugs (NSAIDs and corticosteroids) is a common, but too often abused practice in equine sports medicine, raising significant health and safety concerns. While these drugs provide clinical relief during early stages of musculoskeletal diseases, such an effect stems from blocking pro-inflammatory mediators. However, these same mediators are also required for homeostasis, adaptation to exercise and inflammation resolution. Therefore, anti- inflammatory drugs can interfere with adequate fitness and timely resolution of inflammation increasing the susceptibility to impending catastrophic injuries and chronic inflammation as seen in OA. While these negative side-effects were once believed to result only from the use of corticosteroids, there is growing evidence that even selective anti-inflammatory drugs can impair the production of mediators required for exercise adaptation and inflammation resolution. The aim of this study is to determine how anti-inflammatory drugs interfere with inflammatory mediators involved in exercise adaptation and synovial inflammation resolution. Using a cohort of healthy adult horses subjected to incremental exercise and a model of joint inflammation, serial lipidomics, cytokine quantification, clinical pathology and histology, will be applied to determine the inflammatory and pro-resolving response to musculoskeletal inflammation and anti-inflammatory treatment. Horses not receiving anti-inflammatory drugs will serve as controls.