Cerebral Mechanism of Tuina Analgesia in Management of Knee Osteoarthritis using multimodal MRI: Study Protocol for a Randomized Controlled Trial

Abstract

\n Background: Chronic pain of patients with knee osteoarthritis (KOA) seriously affects the quality of life and leads to the heavy social and economic burden. As one of the representative non-drug therapies in Traditional Chinese Medicine (TCM), Tuina has been generally recognized 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 is a randomized controlled trial with parallel-group design. In total, 60 eligible participants will be randomly assigned to a Tuina group and a health care education group (Education group) in a 1:1 ratio with gender and age matched. The interventions of both groups will last for 30 min per session and be conducted twice each week for 12 weeks. This study will focus on detecting the changes of brain gray matter structure (GM), white matter structure (WM), the cerebral functional connectivity (FC) elicited by Tuina treatment, e.g thalamus, hippocampus, anterior cingulate gyrus, S1, insula, the periaqueductal gray subregions (PAG) etc. The two groups of patients will be evaluated by clinical assessments and multimodal magnetic resonance imaging (MRI) at the baseline and the end of 6 and 12 weeks’ treatment, and still be evaluated by clinical assessments for 48 weeks of follow-up. The Visual Analog Scale (VAS) of current pain, Short-form McGill Pain Questionnaire (SF-MPQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the 36-Item Short Form Health Survey (SF-36), Hamilton Depression Scale (HAMD) and the Hamilton Anxiety Scale (HAMA) will be used to evaluate the pain intensity, pain feeling, pain emotion, clinical symptoms and quality of life respectively. The evaluators and statisticians will be blinded to the group allocation. The repeated measures analysis of variance (2 groups × 6 time points ANOVA) will be employed to analyze 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 randomized controlled trial with clinical assessments and multimodal MRI will help to reveal the influence of Tuina treatment on the potential morphological changes of cortical and subcortical brain structures, the white matter integrity and the functional activities and connectivity of brain regions of patients with KOA, which might provide scientific evidence for the clinical application of Tuina in management of KOA.Trial registration: Chinese Clinical Trial Registry: ChiCTR2000037966. Date of Registration: 8, Sep. 2020. http://www.chictr.org.cn/edit.aspx?pid=61083&htm=4