Physical exercise ameliorates pain, mood alterations and neuroinflammation in a murine model of osteoarthritis

Osteoarthritis (OA) is largely associated with chronic pain, and it is a social and economic problem worldwide. OA pain can lead to psychiatric symptom onset, such as anxiety and depression. Emerging evidence suggest neuroinflammation as a common denominator between OA pain and mood disorders. OA pain pharmacological strategies are often ineffective or cause side effects, therefore, identifying novel non-pharmacological therapeutic approaches, like diet and exercise, could be important. Here, using 8-month-old male C57BL/6 J mice, we evaluated the effect of regular physical exercise on OA pain and related comorbidities. OA was induced by monoiodoacetate-(MIA) administration in knee joint in mice that had undergone physical exercise-(PE) or a sedentary lifestyle-(SL) for two months. After OA induction, mice continued the exercise/not-exercise protocol for another month and subsequently all animals were sacrificed. An in-depth biochemical evaluation (RT-qPCR) was performed at the level of the knee joint, sciatic nerve, dorsal root ganglia, spinal cord and brain areas (brainstem, hypothalamus and hippocampus) and myenteric plexus to evaluate the effect of both OA and exercise on (neuro)inflammation in regions involved in pain and mood regulation. Throughout the experimental protocol, pain-like behavior and motor performance were evaluated, and before sacrifice, mood alterations and metabolic changes were also assessed. Our results showed that OA_SL mice exhibit painful symptoms and mood disturbances. These alterations were also associated with (neuro)inflammation. PE mitigates pain-like behavior and mood alterations and reduces (neuro)inflammation, suggesting that a healthy and active lifestyle may have a positive impact in preventing and/or counteracting OA onset and related comorbidities.