Cerebral mechanism of Tuina analgesia in management of knee osteoarthritis using multimodal MRI: study protocol for a randomised controlled trial.

Background: The chronic pain of patients with knee osteoarthritis (KOA) seriously affects their quality of life and leads to heavy social and economic burden. As a nondrug therapy in Traditional Chinese Medicine (TCM), Tuina is generally recognised as safe and effective for reducing the chronic pain of KOA. However, the underlying central mechanisms of Tuina for improving the pain of KOA are not fully understood.

Methods/design: This study will be a randomised controlled trial with a parallel-group design. A total of 60 eligible participants will be assigned to the Tuina group or healthcare education group (Education group) at 1:1 ratio using stratified randomisation with gender and age as factors. The interventions of both groups will last for 30 min per session and be conducted twice each week for 12 weeks. This study will primarily focus on pain evaluation assessed by detecting the changes in brain grey matter (GM) structure, white matter (WM) structure, and the cerebral functional connectivity (FC) elicited by Tuina treatment, e.g., thalamus, hippocampus, anterior cingulate gyrus, S1, insula, and periaqueductal grey subregions (PAG). The two groups of patients will be evaluated by clinical assessments and multimodal magnetic resonance imaging (MRI) to observe the alterations in the GM, WM, and FC of participants at the baseline and the end of 6 and 12 weeks' treatment and still be evaluated by clinical assessments but not MRI for 48 weeks of follow-up. The visual analogue scale of current pain is the primary outcome. The Short-Form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, 36-Item Short Form Health Survey, Hamilton Depression Scale, and Hamilton Anxiety Scale will be used to evaluate the pain intensity, pain feeling, pain emotion, clinical symptoms, and quality of life, respectively. MRI assessments, clinical data evaluators, data managers, and statisticians will be blinded to the group allocation in the outcome evaluation procedure and data analysis to reduce the risk of bias. The repeated measures analysis of variance (2 groups × 6 time points ANOVA) will be used to analyse numerical variables of the clinical and neuroimaging data obtained in the study. P<0.05 will be the statistical significance level.

Discussion: The results of this randomised controlled trial with clinical assessments and multimodal MRI will help reveal the influence of Tuina treatment on the potential morphological changes in cortical and subcortical brain structures, the white matter integrity, and the functional activities and connectivity of brain regions of patients with KOA, which may provide scientific evidence for the clinical application of Tuina in the management of KOA.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2000037966 . Registered on Sep. 8, 2020.

Dissemination: The results will be published in peer-reviewed journals and disseminated through the study's website, and conferences.