Efficacy and Central Mechanism of Shexiang Zhuifeng Analgesic Plaster Combined with Transcranial Direct Current Stimulation in the Treatment of Knee Osteoarthritis: Study Protocol for a Randomized Controlled Trial

Background: Knee osteoarthritis (KOA) is a chronic pain disorder accompanied by central sensitization, and its treatment remains challenging. While Shexiang Zhuifeng Analgesic Plaster (SZAP) has been shown to effectively alleviate peripheral inflammation and pain, transcranial direct current stimulation (tDCS) can modulate cortical excitability and influence central pain processing. The combination of these two interventions may produce a synergistic “peripheral-central” analgesic effect. This study aims to evaluate the efficacy of this combined approach and utilize neuroimaging techniques to elucidate its underlying central neural mechanisms. Methods: This randomized, controlled, double-blind study will enroll 48 patients with KOA. They will be equally divided into a treatment group and a control group. The treatment group will receive SZAP combined with tDCS, while the control group will receive SZAP combined with sham tDCS. SZAP will be administered once daily, five days per week, and tDCS will be administered three times per week (alternate days) for four weeks. All outcome measures will be measured at baseline and after four weeks of intervention. Efficacy outcomes include visual analogue scale pain scores and the Western Ontario and McMaster Universities Osteoarthritis Index score. The mechanistic analysis focuses on electroencephalogram power spectral density and functional connectivity analysis. Discussion: This study will innovatively combine SZAP with tDCS for the treatment of KOA, based on a comprehensive peripheral and central intervention approach. The study will explore the combined efficacy and analyze its potential central mechanisms. This will not only provide valuable clinical treatment approaches for KOA but will also deepen our understanding of the disease’s mechanisms. Trial Registration: ITMCTR (registration number: ITMCTR2025002557), registered on December 27, 2025, https://itmctr.ccebtcm.org.cn/mgt/project/view/2004717515376295936 . Keywords: knee osteoarthritis, traditional Chinese medicine, Shexiang Zhuifeng Analgesic Plaster, transcranial direct current stimulation, central mechanism, electroencephalogram