Clinical efficacy and safety of a novel acupuncture point combination for knee osteoarthritis: A Randomized Controlled Trial

Introduction: Chronic pain in knee osteoarthritis (KOA) is bidirectionally linked with emotional disorders. This randomized controlled trial evaluated the efficacy and safety of a novel acupuncture point combination for KOA. Methods: Between March 2025 and December 2025, a total of 80 patients were randomized 1:1 to the Novel Acupuncture Point Combination (NAPC) group or the Standard Peri-Knee Acupuncture (PKA) group. Both groups received conventional peri-knee acupuncture treatment, while the NAPC group additionally received acupuncture at the "Three Shen" head points. Treatment was administered 3 times per week for 4 weeks. The primary outcome was the Numerical Rating Scale (NRS). Additional outcomes included the Self-Rating Anxiety Scale (SAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the response rate assessed at weeks 4, 8, and 12, as well as serum 5-hydroxytryptamine (5-HT) levels measured before and after treatment. Outcome assessors and statisticians remained blinded to treatment assignment. All main analyses were by Per-Protocol. Results: Of the 80 participants recruited in the trial, 75 were evaluated for efficacy. Both groups showed significant reductions in NRS, SAS and WOMAC over time (all P < 0.001), with greater pain and anxiety improvement in the NAPC group and a significant group-by-time interaction ( P < 0.05). Serum 5-HT levels increased in both groups, with a larger post-treatment rise in the NAPC group ( P < 0.05). Response rates were consistently higher with NAPC group, although between-group differences were not statistically significant. No serious adverse events were observed. Conclusion: Compared to the peri-knee acupuncture, the novel acupuncture point combination conferred additional benefits in alleviating pain and anxiety, which may be associated with elevated serum 5-HT levels.