Effect of Physical Activity on Chronic Widespread Pain: Insights From Meta-Analysis and Two-Sample Mendelian Randomization

Chongjie Yao,1– 3,* Yuchen Zhang,2,3,* Sizheng Steven Zhao,4 Jun Ren,3 Pingping Sun,5 Lingjun Kong,3 Jiming Tao,3 Jingxian Li,6 Min Fang,3,7 Qingguang Zhu1,7 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4Centre for Musculoskeletal Research, School of Biological Sciences, Faculty of Biological Medicine and Health, the University of Manchester, Manchester, UK; 5School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 6School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, K1N 6N5, Canada; 7Research Institute of Tuina, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingguang Zhu; Min Fang, Email [email protected]; [email protected]: Chronic widespread pain (CWP) is a core symptom of fibromyalgia that is associated with significant morbidity and mortality. Despite the widespread recommendation for physical activity (PA) in management, the heterogeneity of PA prescriptions limits the in-depth evaluation of its efficacy. By triangulating clinical interventional evidence with human genetic evidence, the aim of this study was to investigate the role of influencing factors such as PA mode, course of treatment, and intensity on PA in the prevention and treatment of CWP.Methods: Ten international and regional databases were searched for articles published between January 2014 and July 2024. Randomized control trials with CWP or fibromyalgia as an entry criterion and PA as an intervention were included. Meta-analyses were performed using fixed- or random-effects models based on heterogeneity, and subgroup analyses were conducted. Mendelian randomization (MR) was used to estimate the effects of the genetic variants linked to PA intensity on CWP risk.Results: The analysis included 11 studies with 540 participants. PA effectively improved pain perception (MD: − 1.47; 95% CI: − 2.23, − 0.72), depression (MD: − 4.77; 95% CI: − 7.40, − 2.14), and overall quality of life (SMD: − 1.43; 95% CI: − 2.16, − 0.69). MR analysis revealed that several PA intensities were associated with reduced susceptibility to CWP: walking for pleasure (OR: 0.950; 95% CI: 0.934– 0.966), light do-it-yourself (DIY) (OR: 0.976; 95% CI: 0.961– 0.992), strenuous sports (OR: 0.923; 95% CI: 0.880– 0.967), and other exercises (OR: 0.957; 95% CI: 0.942– 0.973).Conclusion: PA interventions are beneficial for reducing pain perception and mood disorders and enhancing the quality of life of patients with CWP. A treatment course of approximately three months is preferable, with Ba-Duan-Jin potentially more effective than other PAs, and high-intensity PA offers the most significant protective effect against CWP.Keywords: chronic widespread pain, fibromyalgia, physical activity, exercise