Abstract
BACKGROUND: Pain in knee osteoarthritis (KOA) involves maladaptive neuroplastic adaptations within the pain matrix. Tai Chi and transcranial direct current stimulation (tDCS) each alleviate KOA pain, potentially by modulating the dorsolateral prefrontal cortex (DLPFC). Whether combining them yields superior analgesic and neuromodulatory effects remains to be established. METHODS: In this four-arm, parallel-group randomized controlled trial, 152 participants with KOA were allocated to a 12-week intervention: (1) Tai Chi combined with tDCS, (2) Tai Chi, (3) tDCS, or (4) a Health Education Control group. The primary outcome was pain intensity assessed using the Pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included the WOMAC Stiffness and Physical Function subscales, Visual Analogue Scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), Timed Up and Go Test (TUGT), and the 36-Item Short Form Health Survey (SF-36). Resting-state functional connectivity (rsFC) between the right DLPFC and key regions of the pain matrix was analyzed using functional magnetic resonance imaging (fMRI). Assessments were conducted at baseline and post-intervention. RESULTS: The Tai Chi combined with tDCS group demonstrated a significantly greater reduction in WOMAC Pain subscores compared to the Health Education Control group (P < 0.001), the tDCS group (P = 0.003), and the Tai Chi group (P = 0.048). However, the combined intervention did not show statistically superior improvement over Tai Chi group in secondary outcomes. Neuroimaging results indicated that all active interventions decreased rsFC between the right DLPFC and several pain-matrix regions, including the left posterior cingulate cortex, bilateral thalamus, left precuneus, and left superior frontal gyrus. Furthermore, the extent of pain reduction was positively correlated with decreased connectivity between the right DLPFC and both the left posterior cingulate cortex and the left precuneus. CONCLUSIONS: This exploratory trial suggests that combining Tai Chi with tDCS provides superior pain relief compared to either monotherapy in individuals with KOA. Post hoc exploratory neuroimaging analyses further indicate that this analgesic effect may be associated with changes in rsFC between the right DLPFC and regions of the pain matrix. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (ChiCTR2100047287).