The cerebral mechanism of Tuina for treating knee osteoarthritis pain: study protocol for a randomized controlled parallel trial

Abstract Background: Despite the high prevalence and socioeconomic impact of knee osteoarthritis (KOA), treatments for KOA are often unsatisfactory, with wide variation in effectiveness across patients. Tuina is one treatment that is frequently prescribed for patients with KOA. However, how Tuina influences the activity of the central nervous system to alleviate KOA pain remains unclear. Our randomized controlled parallel trial was designed to address this gap through a comparative evaluation of the effect of Tuina on the resting-state functional connectivity (rsFC) of the brain in patients with KOA compared to treatment using celecoxib as the control.Methods/design: This will be a randomized controlled parallel trial to be conducted between June 2022 and June 2024. Forty-eight participants with KOA will be enrolled and randomly allocated to one of two groups, the Tuina treatment group or the celecoxib (control) group. Participants in each of the two groups will undergo 6 weeks treatment. Resting-state functional magnetic resonance imaging (fMRI) will be performed to quantify rsFC at baseline, before treatment, and at the end of the intervention, where rsFC will be used to evaluate the effects of treatment on brain activity. The following self-reported scales will be used as clinical measures of symptomology: the Numerical Rating Scale to quantify the severity of pain, the Pain Catastrophizing Scale to quantify emotional response to pain, and the Hamilton Anxiety Scale and the Hamilton Depression Scale to quantify the cognitive response to pain. Scale scores will be obtained before and after treatment to measure clinical change. Adverse events will be documented and assessed throughout the trial.Discussion: The results of our trial will provide evidence of the effect of Tuina treatment on the rsFC of patients with KOA and identify the possible relationship between a change in the rsFC and improvement of clinical variables, thus elucidating the central mechanism by which Tuina improves pain in KOA.Trial registration: Registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/searchproj.aspx, ChiCTR2100045990). Date of registration: 1 May 2021.