经颅电刺激镇痛研究的现状及展望

经颅电刺激技术是一种非侵入性神经调控方法，因其具有卓越的安全性、良好的患者依从性以及高度便携性等特点，被视为一种潜在的非药物镇痛手段。然而，目前对于经颅电刺激镇痛效果的研究结果不一致且镇痛机制尚未完全阐明。本文通过系统归纳总结3种主要的经颅电刺激技术——经颅直流电刺激、经颅交流电刺激和经颅随机噪声刺激——在镇痛领域的研究进展，评估了这些技术对短时、急性和慢性疼痛的镇痛效果，并深入剖析了其潜在的镇痛机制。同时，本文系统讨论了既往研究的局限性，并对未来研究提出了一系列切实可行的建议，如借助电场模拟技术实现个性化刺激以克服不同个体头部解剖结构差异的影响、应用多位点刺激和深部脑刺激技术来拓展刺激脑区、搭建经颅电刺激技术同步神经影像平台以制定个体特异性的刺激方案并深入揭示其镇痛机制、探索与其他治疗技术的联合应用以提高疗效等。这些建议的实施将有助于解决当前研究中存在的问题，充分发挥经颅电刺激在疼痛治疗中的临床价值，最终实现患者疼痛的缓解。

Recent Progress and Future Directions of Transcranial Electrical Stimulation for Analgesia

Transcranial electrical stimulation (tES) is a non-invasive neural modulation technique known for its high safety, patient compliance, and portability. It holds promise as a potential non-pharmacological method for analgesia. However, challenges persist in utilizing tES for pain management, including inconsistent research findings and limited understanding of its analgesic mechanisms. Therefore, by summarizing the advances in the analgesic researches employing the 3 primary tES techniques, transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), we reviewed the analgesic effects on both acute and chronic pain, as well as the neural mechanisms underlying the analgesic effect of each technique. Accumulating evidence suggests that the analgesic effects of tDCS are significant, but studies on analgesic effects of tACS and tRNS remain limited. And the exact mechanisms of pain relief through tES turned out to be not yet well established. Furthermore, we systematically discussed the limitations of analgesia-related studies employing tES techniques across various aspects, involving research design, stimulation protocol formulation, neural response observation, analgesic effect assessment, and safety considerations. To address these limitations and advance clinical translation, we emphasized utilizing promising stimulation techniques and offered practical suggestions for future research endeavors. Specifically, employing numerical simulation of electric field guided by magnetic resonance imaging (MRI) would reduce variability of outcomes due to individual differences in head anatomy. For this purpose, it is advisable to establish standardized head models based on MRI data from the Chinese populations and validate simulated electric field results in tES research to diminish confounding factors concerning anatomy. Meanwhile, novel techniques like multi-site brain stimulation and interferential stimulation (IFS) could broaden the range of stimulation sites in both scope and depth. Multi-site brain stimulation facilitates modulation of entire neural networks, enabling more sophisticated investigations into the complexity of pain. IFS can reach deep brain tissues without invasive surgical procedures, achieving more comprehensive modulation. Regarding neural response observations, establishing a tES-neuroimaging synchronized platform would enable revealing its mechanisms and personalizing protocols based on inter-subject neural response variability detected through recordings. By integrating tES with various neuroimaging techniques, such as functional MRI, electroencephalography (EEG) and magnetoencephalography, into one unified platform, researchers could examine brain activities in baseline before stimulation, dynamic changes in brain activities during stimulation, and sustained brain responses after stimulation. Additionally, collecting finer-grained data on participant characteristics and pain intensity would enhance the sensitivity of future studies. In designing clinical trials to evaluate chronic pain treatments and reporting the results, adopting the six core outcome domain measures recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) could prove beneficial. Lastly, safety considerations can never be overemphasized in future tES studies especially when combining tES with MRI and EEG techniques. These efforts may help to broaden the research scope, reconcile inconsistencies in findings and elucidate the analgesic mechanisms of tES, thus facilitating the development of pragmatic pain management strategies such as combination therapies and home therapies. Ultimately, these suggestions will maximize the clinical application value of tES in pain treatment to achieve pain relief for patients.