Xu Hao-Ran, Yi Yiu-Liang, Xue Chuan, Guo Zi-Qi, Ding Li, Jia Jie
Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.
National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
J Headache Pain. 2025 Jul 22;26(1):166. doi: 10.1186/s10194-025-02096-y.
Low-intensity transcranial ultrasound stimulation (LITUS) is an emerging non-invasive neuromodulation technique for pain treatment, with the unique ability to modulate deep brain nuclei associated with pain. The aim of this study is to systematically review and summarize the evidence for the efficacy of LITUS in pain management and to elucidate the potential mechanisms underlying its analgesic effects.
A systematic search was conducted across five databases up to Mar 31st, 2025. Controlled studies in both human and animal subjects were included. Two independent reviewers completed the screening and risk of bias assessment process following predefined inclusion and exclusion criteria.
A total of thirteen studies were included in the review. These studies demonstrated LITUS's potential in managing various types of pain among different populations and animal models, particularly targeting the anterior cingulate cortex, thalamus, insular cortex, primary sensorimotor cortex, and periaqueductal gray. Most included studies showed positive effects and verified the safety of LITUS on pain, reporting few adverse effects.
LITUS is an effective and non-invasive tool for pain regulation in animals and humans, enabling precise modulation of deep brain circuits. Analgesic effects may be affected by pain-related risk factors, insufficient dosage, suboptimal protocols, and target selection. Initial evidence has highlighted the direct link between LITUS parameters, brain region responses, and pain behavior. Modulation of brain excitatory, nociceptive circuit, electrophysiological response, autonomic response, biochemistry, neuroinflammation, and psychology are proposed as the potential mechanisms underlying the efficacy of LITUS. More high-quality research is urgently needed to advance clinical LITUS use and reveal its mechanisms.
低强度经颅超声刺激（LITUS）是一种新兴的用于疼痛治疗的非侵入性神经调节技术，具有调节与疼痛相关的深部脑核团的独特能力。本研究的目的是系统回顾和总结LITUS在疼痛管理中的疗效证据，并阐明其镇痛作用的潜在机制。
截至2025年3月31日，在五个数据库中进行了系统检索。纳入了对人类和动物受试者的对照研究。两名独立 reviewers 根据预先定义的纳入和排除标准完成了筛选和偏倚风险评估过程。
本综述共纳入13项研究。这些研究证明了LITUS在不同人群和动物模型中管理各种类型疼痛的潜力，特别是针对前扣带回皮质、丘脑、岛叶皮质、初级感觉运动皮质和导水管周围灰质。大多数纳入研究显示了积极效果，并证实了LITUS对疼痛的安全性，报告的不良反应很少。
LITUS是一种用于动物和人类疼痛调节的有效且非侵入性的工具，能够精确调节深部脑回路调节。镇痛效果可能受疼痛相关危险因素、剂量不足、方案欠佳和靶点选择的影响。初步证据突出了LITUS参数、脑区反应和疼痛行为之间的直接联系。脑兴奋性、伤害性回路、电生理反应、自主反应、生物化学、神经炎症和心理学的调节被认为是LITUS疗效的潜在机制。迫切需要更多高质量的研究来推进LITUS的临床应用并揭示其机制。
