Kang Yi, Tang Yidan, Gao Jun, Qiu Yong, Kong Weishuang, Zhu Tao, Chen Guo
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, P.R. China; Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, P.R. China.
Department of Surgery, Xuanwei Hospital of Traditional Chinese Medicine, Xuanwei, P.R. China.
Pain Physician. 2025 Jul;28(4):E371-E384.
Spinal cord stimulation (SCS) is an effective surgical intervention for treating chronic neuropathic pain conditions that are refractory to other management options, such as opioids, physical therapy, nerve blocks, or radiofrequency ablation. It is currently clinically approved as the main therapeutic procedure for persistent low back pain. As we understand these mechanisms better, SCS could have novel clinical applications. For this reason, an accurate understanding of research progress into the molecular and circuit mechanisms of SCS is indispensable for enhancing its effectiveness, safety, and future applications.
This review aims to systematically discuss the molecular mechanisms of spinal cord electrical stimulation, from its action sites and transmitter interactions to the supraspinal circuit, to reveal the biological basis behind these mechanisms further and provide a more solid theoretical foundation and scientific basis for the clinical application of SCS.
Narrative review.
Our research was conducted in PubMed, Ovid MEDLINE, and Embase. Boolean operators were used to combine MeSH (Medical Subject Headings) terms and keywords such as "spinal cord stimulation," "chronic neuropathic pain," "electric stimulation therapy," "analgesic mechanism," "spinal cord dorsal horn," "central sensitization," "neural circuits," and "neurotransmitter function".
Numerous retrospective clinical studies and randomized controlled trials have yielded results supporting the remarkable efficacy and broad development prospects of SCS. However, the effectiveness and safety of SCS in certain diseases are still insufficiently studied, and the related molecular mechanisms are not well developed. We present a comprehensive, up-to-date overview and elaboration of the neurophysiological, biochemical, anti-inflammatory, and neurocirculatory mechanisms that have been associated with the use of spinal cord electrical stimulation for treating chronic pain.
There exists an inconsistency in SCS animal experimental models.
Our findings from available studies include the molecular mechanisms involved in SCS on chronic pain, new paradigms for spinal cord electrical stimulation therapy, and explain their underlying biological processes, as well as the pros and cons of SCS in terms of its effectiveness in clinical use. With a better understanding of SCS's mechanisms, we may gain a more in-depth understanding of the current insights about the analgesic mechanisms of action underlying SCS for chronic neuropathic pain treatment.
脊髓刺激（SCS）是一种有效的外科干预手段，用于治疗对其他治疗方法（如阿片类药物、物理治疗、神经阻滞或射频消融）无效的慢性神经性疼痛疾病。目前，它在临床上被批准为持续性腰痛的主要治疗方法。随着我们对这些机制的理解不断深入，SCS可能会有新的临床应用。因此，准确了解SCS分子和回路机制的研究进展对于提高其有效性、安全性及未来应用至关重要。
本综述旨在系统地探讨脊髓电刺激的分子机制，从其作用位点、递质相互作用到脊髓上回路，以进一步揭示这些机制背后的生物学基础，并为SCS的临床应用提供更坚实的理论基础和科学依据。
叙述性综述。
我们在PubMed、Ovid MEDLINE和Embase数据库中进行了研究。使用布尔运算符组合医学主题词（MeSH）和关键词如“脊髓刺激”“慢性神经性疼痛”“电刺激疗法”“镇痛机制”“脊髓背角”“中枢敏化”“神经回路”和“神经递质功能”。
大量回顾性临床研究和随机对照试验的结果支持了SCS显著的疗效和广阔的发展前景。然而，SCS在某些疾病中的有效性和安全性仍研究不足，相关分子机制也未充分阐明。我们全面、最新地概述并阐述了与使用脊髓电刺激治疗慢性疼痛相关的神经生理、生化、抗炎和神经循环机制。
SCS动物实验模型存在不一致性。
我们从现有研究中获得的结果包括SCS对慢性疼痛的分子机制、脊髓电刺激治疗的新范式，并解释了其潜在生物学过程，以及SCS在临床应用有效性方面的优缺点。通过更好地理解SCS机制，我们可能会更深入地了解目前关于SCS用于治疗慢性神经性疼痛的镇痛作用机制的见解。
