Obesity-associated metabolic inflammation and chronic musculoskeletal pain: Pathophysiological mechanisms and clinical implications of weight loss

Obesity is associated with chronic low-grade systemic inflammation, metabolic dysfunction, and increased mechanical loading, factors that may contribute to the development and persistence of chronic musculoskeletal pain. This study aimed to analyze the pathophysiological mechanisms linking obesity-related metabolic inflammation to chronic musculoskeletal pain and to examine the clinical implications of weight loss for pain management and functional recovery. A literature-based investigation was conducted through a qualitative synthesis of experimental, observational, and interventional evidence addressing adipose tissue dysfunction, inflammatory mediators, nociceptive sensitization, and weight management strategies. The reviewed evidence indicates that adipose tissue acts as an immunometabolic organ and that inflammatory signaling may interact with biomechanical stress and peripheral and central pain-processing mechanisms. Clinical trials involving individuals with knee osteoarthritis and overweight or obesity demonstrate that structured dietary interventions, particularly when combined with exercise, can improve pain-related outcomes and physical function. However, these findings cannot be uniformly extrapolated to other chronic pain conditions. Sleep disturbances, psychological stress, emotional factors, and individual clinical circumstances may further influence pain perception, treatment adherence, and therapeutic outcomes. The findings support an individualized, multidisciplinary approach integrating weight management, physical activity, patient education, and biopsychosocial assessment. Further research is needed to clarify causal mechanisms and determine the effectiveness of these strategies across different chronic musculoskeletal pain populations.