Different exercise modalities relieve pain syndrome in patients with knee osteoarthritis and modulate the dorsolateral prefrontal cortex: A multiple mode MRI study.

OBJECTIVES: Knee osteoarthritis (KOA) is a common degenerative joint disease with no satisfactory intervention. Recently, both physical and mindfulness exercises have received considerable attention for their implications in KOA pain management, and the dorsolateral prefrontal cortex (DLPFC) has displayed a critical role in pain modulation. This study aimed to comparatively investigate the modulation effects of different exercises using multidisciplinary measurements. METHODS: 140 KOA patients were randomized into Tai Chi, Baduanjin, stationary cycling, or health education control groups for 12 weeks. Knee Injury and Osteoarthritis Outcome Score (KOOS), resting state functional magnetic resonance imaging (fMRI), structural MRI, and serum biomarkers were measured at baseline and at the end of the study. RESULTS: We found: 1) increased KOOS pain subscores (pain reduction) and serum programmed cell death protein 1 (PD-1) levels in the three exercise groups compared to the control group; 2) decreased resting state functional connectivity (rsFC) of the DLPFC-supplementary motor area (SMA) and increased rsFC between the DLPFC and anterior cingulate cortex in all exercise groups compared to the control group; 3) significant associations between DLPFC-SMA rsFC with KOOS pain subscores and serum PD-1 levels at baseline; 4) significantly increased grey matter volume in the SMA in the Tai Chi and stationary cycling groups, and a trend toward significant increase in the Baduanjin group compared to the control group; 5) significant DLPFC rsFC differences among different exercise groups; and 6) that baseline DLPFC-SMA rsFC can predict the effect of mind-body exercise on pain improvement in KOA. CONCLUSION: Our results suggest that different exercises can modulate both common and unique DLPFC (cognitive control) pathways, and altered DLPFC-SMA rsFC is associated with serum biomarker levels. Our findings also highlight the potentials of neuroimaging biomarkers in predicting the therapeutic effect of mind-body exercises on KOA pain.

Modulatory effects of different exercise modalities on the functional connectivity of the periaqueductal grey and ventral tegmental area in patients with knee osteoarthritis: a randomised multimodal magnetic resonance imaging study.

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.

The modulation effects of the mind-body and physical exercises on the basolateral amygdala-temporal pole pathway on individuals with knee osteoarthritis.

Background/Objective: To investigate the modulatory effects of different physical exercise modalities on connectivity of amygdala subregions and its association with pain symptoms in patients with knee osteoarthritis (KOA). Methods: 140 patients with KOA were randomly allocated either to the Tai Chi, Baduanjin, Stationary cycling, or health education group and conducted a 12 week-long intervention in one of the four groups. The behavioral, magnetic resonance imaging (MRI), and blood data were collected at baseline and the end of the study. Results: Compared to the control group, all physical exercise modalities lead to significant increases in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (pain relief) and serum Programmed Death-1 (PD-1) levels. Additionally, all physical exercise modalities resulted in decreased resting state functional connectivity (rsFC) of the basolateral amygdala (BA)-temporal pole and BA-medial prefrontal cortex (mPFC). The overlapping BA-temporal pole rsFC observed in both Tai Chi and Baduanjin groups was significantly associated with pain relief, while the BA-mPFC rsFC was significantly associated with PD-1 levels. In addition, we found increased fractional anisotropy (FA) values, a measurement of water diffusion anisotropy of tissue that responded to changes in brain microstructure, within the mind-body exercise groups' BA-temporal pole pathway. The average FA value of this pathway was positively correlated with KOOS pain score at baseline across all subjects. Conclusions: Our findings suggest that physical exercise has the potential to modulate both functional and anatomical connectivity of the amygdala subregions, indicating a possible shared pathway for various physical exercise modalities.

The modulation effects of the mind-body and physical exercises on the basolateral amygdala-temporal pole pathway on individuals with knee osteoarthritis / Los efectos de modulación de la mente-cuerpo y los ejercicios físicos en la vía del polo basolateral amígdala-temporal en personas con osteoartritis de rodilla

Background/Objective: To investigate the modulatory effects of different physical exercise modalities on connectivity of amygdala subregions and its association with pain symptoms in patients with knee osteoarthritis (KOA). Methods: 140 patients with KOA were randomly allocated either to the Tai Chi, Baduanjin, Stationary cycling, or health education group and conducted a 12 week-long intervention in one of the four groups. The behavioral, magnetic resonance imaging (MRI), and blood data were collected at baseline and the end of the study. Results: Compared to the control group, all physical exercise modalities lead to significant increases in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (pain relief) and serum Programmed Death-1 (PD-1) levels. Additionally, all physical exercise modalities resulted in decreased resting state functional connectivity (rsFC) of the basolateral amygdala (BA)-temporal pole and BA-medial prefrontal cortex (mPFC). The overlapping BA-temporal pole rsFC observed in both Tai Chi and Baduanjin groups was significantly associated with pain relief, while the BA-mPFC rsFC was significantly associated with PD-1 levels. In addition, we found increased fractional anisotropy (FA) values, a measurement of water diffusion anisotropy of tissue that responded to changes in brain microstructure, within the mind-body exercise groups' BA-temporal pole pathway. The average FA value of this pathway was positively correlated with KOOS pain score at baseline across all subjects. Conclusions: Our findings suggest that physical exercise has the potential to modulate both functional and anatomical connectivity of the amygdala subregions, indicating a possible shared pathway for various physical exercise modalities.(AU)