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Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain

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Abstract

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.

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Acknowledgement

We thank Beijing PINS Medical Co., Ltd., China for technical assistance. Special thanks go to Fu Xu (Beijing PINS Medical Co., Ltd.) and colleagues for modifying the SCS equipment for animal studies. This work was supported by the National Key Research and Development Program of the Ministry of Science and Technology, China (2016YFC0105501, 2019YFD1712000).

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Author notes

  1. Fu-Jun Zhai and Song-Ping Han contributed equally to this work.

Authors and Affiliations

  1. Neuroscience Research Institute, Peking University, Beijing, 100191, China

    Fu-Jun Zhai, Tian-Jia Song, Ran Huo, Xing-Yu Lan, Rong Zhang & Ji-Sheng Han

  2. Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China

    Fu-Jun Zhai, Tian-Jia Song, Ran Huo, Xing-Yu Lan, Rong Zhang & Ji-Sheng Han

  3. Key Laboratory for Neuroscience, Ministry of Education, National Health Commission, Peking University, Beijing, 100191, China

    Fu-Jun Zhai, Tian-Jia Song, Ran Huo, Xing-Yu Lan, Rong Zhang & Ji-Sheng Han

  4. Wuxi HANS Health Medical Technology Co., Ltd., Wuxi, 214122, China

    Song-Ping Han

  5. Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, China

    Rong Zhang

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  1. Fu-Jun Zhai
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Correspondence to Rong Zhang or Ji-Sheng Han.

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Zhai, FJ., Han, SP., Song, TJ. et al. Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain. Neurosci. Bull. 38, 403–416 (2022). https://doi.org/10.1007/s12264-022-00844-7

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