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Electroacupuncture Alleviates Neuropathic Pain by Suppressing Ferroptosis in Dorsal Root Ganglion via SAT1/ALOX15 Signaling

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Abstract

Neuropathic pain affects globally about 7–10% of the general population. Electroacupuncture (EA) effectively relieves neuropathic pain symptoms without causing any side effects; however, the underlying molecular mechanisms remain unclear. We established a chronic constriction injury (CCI)-induced rat model of neuropathic pain. RNA sequencing was used to screen for differentially expressed genes in the dorsal root ganglion after CCI and EA treatment. We identified gene markers of ferroptosis spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15) to be dysregulated in the CCI-induced neuropathic pain model. Furthermore, EA relieved CCI-induced pain as well as ferroptosis-related symptoms in the dorsal root ganglion, including lipid peroxidation and iron overload. Finally, SAT1 knockdown also alleviated mechanical and thermal pain hypersensitivity and reversed ferroptosis damage. In conclusion, we showed that EA inhibited ferroptosis by regulating the SAT1/ALOX15 pathway to treat neuropathic pain. Our findings provide insight into the mechanisms of EA and suggest a novel therapeutic target for neuropathic pain.

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Data Availability

All the data supporting the findings of this study are available within the article and from the corresponding author upon reasonable request.

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Acknowledgements

Thanks to the funding support from the National Natural Science Foundation of China.

Funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81973949 and 81804187).

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Authors and Affiliations

  1. Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China

    Kexing Wan, Yuye Lan, Suixi Wang, Kailing Zhang, Zixiao Wang, Lei Pei, Yongmin Liu & Man Li

  2. Clinical Laboratories, Wuhan First Hospital, Wuhan, 430030, China

    Min Jia

  3. School of Clinical Medicine, Hubei University of Science and Technology, Xianning, 437000, China

    Hong Zhang

  4. Department of Clinical Research Institute, Central People’s Hospital of Zhanjiang, Zhanjiang, 524000, China

    He Zhu, Xunan Zheng & Yi Luo

  5. Department of Acupuncture, Wuhan First Hospital, Wuhan, 430030, China

    Caihua Wu

  6. Department of Physiology, Medical College of Shihezi University, Shihezi, 832002, China

    Yongmin Liu

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  1. Kexing Wan
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Contributions

Man Li, Yongmin Liu, and Caihua Wu conceived and designed the research and drafted and revised the manuscript. Kexing Wan and Min Jia performed the experiments. Hong Zhang, Yuye Lan, and Suixi Wang helped to analyze the data and interpreted the results of the experiments. Kexing Wan prepared the figures. Lei Pei and He Zhu guided the experimental design. Kailing Zhang, Zixiao Wang, Xunan Zheng, and Yi Luo provided experimental help. All authors approved the final edited version of the manuscript.

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Correspondence to Caihua Wu, Yongmin Liu or Man Li.

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All experimental procedures were carried out following the ethical guidelines of the International Association for the Study of Pain (Zimmermann 1983) and approved by the Institutional Animal Care and Use Committee (IACUC) of Huazhong University of Science and Technology.

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Wan, K., Jia, M., Zhang, H. et al. Electroacupuncture Alleviates Neuropathic Pain by Suppressing Ferroptosis in Dorsal Root Ganglion via SAT1/ALOX15 Signaling. Mol Neurobiol 60, 6121–6132 (2023). https://doi.org/10.1007/s12035-023-03463-z

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