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Bo Wang,1,* Fan Yu,2,* Yantao Ma,1 Huiying Zhao,2 Wei Wu,3,* Yongjun Zheng1,* 1Department of Pain Management, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2School of Exercise and Health, Shanghai University of Sport, Shanghai, People’s Republic of China; 3School of Athletic Performance, Shanghai University of Sport, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongjun Zheng, Department of Pain Management, Huadong Hospital, Fudan University, 221 West Yan’an Road, Shanghai, People’s Republic of China, Email zhengyongjun1971@126.com Wei Wu, School of Athletic Performance, Shanghai University of Sport, 188 Hengren Road, Shanghai, People’s Republic of China, Email wuwei1@sus.edu.cnBackground: Chronic pain (CP) represents the most prevalent form of pain experienced by patients. Among various conservative treatment modalities, music listening has emerged as a safe and effective strategy for pain management. However, the specific effects of music therapy (MT) on individuals with CP remain insufficiently understood. Therefore, this study aims to evaluate the efficacy of MT in patients with CP.Methods: A total of 79 participants were randomly assigned to either the experimental group (EG) or the control group (CG). The EG received MT (receptive music listening) combined with health education, while the CG received health education alone. The primary outcome measure was the Simplified McGill Pain Questionnaire (SF-MPQ). Secondary outcome measures included the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), the Pittsburgh Sleep Quality Index (PSQI), and heart rate variability (HRV). Assessments for the EG were conducted at baseline, immediately after the intervention, and two weeks post-intervention. The CG was assessed at baseline and two weeks post-intervention.Results: Following treatment, the EG demonstrated significantly greater improvements in PHQ-9 scores and the low-frequency/high-frequency (LF/HF) ratio of HRV compared to the CG. Although both groups exhibited improvement over time, there were no statistically significant inter-group differences in total SF-MPQ scores post-intervention; however, the Present Pain Intensity (PPI) sub-score was significantly lower in the EG Furthermore, no significant inter-group differences were observed regarding anxiety or sleep outcomes.Conclusion: Music listening was found to may alleviate pain severity in patients with CP. Additionally, our findings indicate that MT can effectively reduce depressive symptoms, a common and disabling complication among individuals with CP. Furthermore, the observed modulation of the LF/HF ratio suggests that MT may regulate the balance of sympathetic and parasympathetic nervous system activity in these patients. These results suggest that MT can serve as an effective adjunctive intervention in the management of CP.Trial Registration: Registered in the Chinese Clinical Trial Registry (www.chictr.org.cn) on 01/06/2025 with the following code: ChiCTR-INR-2500095297.Keywords: music therapy, chronic pain, heart rate variability, autonomic nervous