Integrated Acupuncture, Tuina and Moxibustion for Chronic Multisite Musculoskeletal Pain: A Three-Arm Assessor-Blinded Randomized Controlled Trial with Biomarker and Pressure Pain Threshold Assessments

Background: Chronic multisite musculoskeletal pain (CMMP) impairs physical function and sleep globally. Pharmacotherapy carries diverse adverse reactions, while combined TCM external therapies are widely applied clinically. High-quality three-arm RCT evidence verifying the incremental benefit of supplementary moxibustion based on acupuncture plus Tuina remains scarce, and few trials integrate pressure pain threshold (PPT) and circulating inflammatory markers as objective endpoints. Objective: To compare clinical outcomes of triple combined therapy versus acupuncture-Tuina alone and standardized rehabilitation, and explore potential correlations between symptom improvement and changes in PPT, inflammatory and endogenous analgesic biomarkers. Methods: A prospective single-center assessor-blinded three-arm RCT following CONSORT & STRICTA guidelines; approved by institutional ethics committee and prospectively registered before participant enrolment. A total of 156 eligible patients (n=52 per group, 1:1:1 randomization) received 8-week treatment (3 sessions weekly), with follow-ups at week 4, 8, 12, 24. Primary endpoint: week-8 adjusted NRS change from baseline; secondary outcomes contained regional pain scores, multi-dimensional functional scales, PPT, PSQI, EQ-5D-5L (Global Burden of Disease Collaborative Network, 2024), weekly paracetamol intake and four serum biomarkers. ITT as primary analysis, PP for sensitivity; multiple imputation (20 datasets), linear mixed model and ANCOVA were adopted, Bonferroni correction for secondary pairwise comparisons. Results: 196 candidates screened, 40 excluded, 156 randomized; 11 withdrew within 8 weeks, another 8 lost to follow-up between week8–24; 145 finished 8-week intervention, 137 completed 24-week follow-up. All baseline indexes were balanced across three groups (P＞0.05). At week 8, integrated group yielded superior NRS reduction vs acupuncture-Tuina (adjusted MD = −1.12, 95% CI −1.68~−0.56, P＜0.001, Cohen’s d=0.74) and rehabilitation (adjusted MD = −2.26, 95% CI −2.83~−1.69, P＜0.001, Cohen’s d=1.18), and the inter-group difference slightly exceeded predefined MCID=1.0. The triple regimen brought consistent improvements in regional pain, physical function, PPT, sleep and life quality alongside obvious analgesic reduction. Serum pro-inflammatory factors declined and β-endorphin increased more prominently in combined cohort. Only mild self-limited adverse events were documented without serious incidents. Conclusion: Adding moxibustion onto fixed acupuncture-Tuina produces statistically and clinically meaningful extra benefits for CMMP in pain relief, myofascial hypersensitivity alleviation and functional recovery, accompanied by reduced rescue analgesic usage. Decreased systemic inflammation and elevated endogenous opioid levels are potentially associated with clinical improvements rather than confirmed causal drivers. Further multicenter sham-controlled trials are required for external validation.