Inflammatory and Neurofunctional Markers in Therapeutic Exercise Response: A Randomized Trial Synthesis on Articular Pain Management

• Shwetambari Korde

  Author

Chronic musculoskeletal pain involving joints and spine is a major cause of functional limitation in rehabilitation populations. Although exercise therapy is widely used in clinical practice, the biological mechanisms linking symptom improvement to physiological change are not fully established. This review investigates how structured exercise interventions affect both molecular markers and functional outcomes in individuals with non-cancer chronic musculoskeletal pain. Five randomized controlled trials (n = 312) meeting quality criteria were assessed using the Cochrane Risk of Bias 2 tool. Interventions included resistance training, mind-body practices such as Tai Chi and Baduanjin, sensorimotor exercises, and virtual reality–assisted rehabilitation, lasting 4 to 12 weeks. Outcomes included pain intensity and biomarkers related to inflammation, cartilage and bone metabolism, neurotrophic activity, and neuroimaging findings. Across studies, exercise consistently reduced pain intensity. Improvements were often accompanied by reductions in inflammatory biomarkers and alterations in neuroimaging outcomes, including changes in gray matter structure and pain-related connectivity. In contrast, markers of cartilage degradation and bone metabolism showed inconsistent or minimal association with pain reduction. A quantitative meta-analysis was not conducted due to variability in study design and biomarker selection. Overall, the evidence suggests that exercise relieves pain through combined peripheral and central mechanisms involving immune regulation, tissue-level adaptation, and neural plasticity. These findings reinforce the value of exercise in rehabilitation and highlight the need for standardized biomarker frameworks and study designs to support precision-based approaches in future research.

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