Jiao Liu1, Lidian Chen2, Xiangli Chen3, Kun Hu4, Youxue Tu4, Meiqin Lin4, Jia Huang4, Weilin Liu4, Jinsong Wu4, Zhijie Qiu4, Jingfang Zhu4, Ming Li5, Joel Park6, Georgia Wilson6, Courtney Lang6, Guanli Xie4, Jing Tao7, Jian Kong6. 1. National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, China; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. 2. College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China; Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China. 3. Department of Rehabilitation Psychology and Special Education, University of Wisconsin-Madison, Madison, WI, USA. 4. College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China. 5. Affiliated Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, China. 6. Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. 7. College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China. Electronic address: taojing01@163.com.
Abstract
BACKGROUND: Knee osteoarthritis is a prevalent disorder with unsatisfactory treatment options. Both physical and mindful exercises may be able to relieve its pain symptoms. We compared the modulatory effects of different exercise modalities on the periaqueductal grey (PAG) and ventral tegmental area (VTA), which play important roles in descending opioidergic pathways and reward/motivation systems in patients with knee osteoarthritis. METHODS: We recruited and randomised 140 patients into Tai Chi, Baduanjin, stationary cycling, and health education control groups for 12 weeks. Knee injury and Osteoarthritis Outcome Score (KOOS), functional and structural MRI, and blood biomarkers were measured at the beginning and end of the experiment. We used the PAG and VTA as seeds in resting-state functional connectivity (rsFC) analysis. RESULTS: Compared with the control group: (i) all exercises significantly increased KOOS pain sub-scores (pain reduction) and serum programmed death 1 (PD-1) concentrations; (ii) all exercises decreased right PAG rsFC with the medial orbital prefrontal cortex, and the decreased rsFC was associated with improvements in knee pain; and (iii) grey matter volume in the medial orbital prefrontal cortex was significantly increased in all exercise groups. There was also significantly decreased rsFC between the left VTA and the medial orbital prefrontal cortex in the Tai Chi and Baduanjin groups. CONCLUSIONS: Exercise can simultaneously modulate the rsFC of the descending opioidergic pathway and reward/motivation system and blood inflammation markers. Elucidating the shared and unique mechanisms of different exercise modalities may facilitate the development of exercise-based interventions for chronic pain. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-16009308.
RCT Entities:
BACKGROUND:Knee osteoarthritis is a prevalent disorder with unsatisfactory treatment options. Both physical and mindful exercises may be able to relieve its pain symptoms. We compared the modulatory effects of different exercise modalities on the periaqueductal grey (PAG) and ventral tegmental area (VTA), which play important roles in descending opioidergic pathways and reward/motivation systems in patients with knee osteoarthritis. METHODS: We recruited and randomised 140 patients into Tai Chi, Baduanjin, stationary cycling, and health education control groups for 12 weeks. Knee injury and Osteoarthritis Outcome Score (KOOS), functional and structural MRI, and blood biomarkers were measured at the beginning and end of the experiment. We used the PAG and VTA as seeds in resting-state functional connectivity (rsFC) analysis. RESULTS: Compared with the control group: (i) all exercises significantly increased KOOS pain sub-scores (pain reduction) and serum programmed death 1 (PD-1) concentrations; (ii) all exercises decreased right PAG rsFC with the medial orbital prefrontal cortex, and the decreased rsFC was associated with improvements in knee pain; and (iii) grey matter volume in the medial orbital prefrontal cortex was significantly increased in all exercise groups. There was also significantly decreased rsFC between the left VTA and the medial orbital prefrontal cortex in the Tai Chi and Baduanjin groups. CONCLUSIONS: Exercise can simultaneously modulate the rsFC of the descending opioidergic pathway and reward/motivation system and blood inflammation markers. Elucidating the shared and unique mechanisms of different exercise modalities may facilitate the development of exercise-based interventions for chronic pain. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-16009308.
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