Liu Yinglu, Guo Shengli, Li Yang, Mao Jingrui, Lin Xiaoxue, Liu Ruozhuo, Zhao Dengfa, Dong Zhao, Yu Shengyuan, Han Xun
Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
Department of Neurosurgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
J Headache Pain. 2025 Mar 28;26(1):61. doi: 10.1186/s10194-025-02006-2.
Clinical observations have shown that transcutaneous occipital nerve stimulation (tONS) is effective in treating migraine. However, the underlying mechanisms are poorly understood. This study employs a rodent model to investigate the therapeutic effects of tONS on migraine-related pain and to explore potential mechanisms.
The SD rats were used to establish the migraine model by repeated epidural infusions of inflammatory soup (IS). Modified bilateral electrodes were attached noninvasively for tONS treatments. Periorbital mechanical thresholds were assessed using von-Frey filaments, and other pain-related nociceptive behaviors were analyzed through video recordings. The expressions of c-Fos, synaptophysin (Syp) and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and/or periaqueductal gray (PAG) area were measured by immunofluorescence and western blotting analyses. The excitatory synaptic transmission in the PAG was detected by whole-cell patch-clamp recording among migraine rats.
The reduction in periorbital mechanical thresholds induced by repeated IS infusions was partially reversed by tONS treatments in migraine rats. Other pain-related behaviors, including exploration, rest, and unilateral grooming, consistently improved following tONS treatment. The TNC and PAG area were activated after IS modeling, and the CGRP expressions in the PAG significantly decreased after tONS treatments. tONS could inhibit the enhanced excitatory synaptic transmission in the PAG of migraine rats.
Our findings suggest that tONS has therapeutic potential in treating migraine, with the PAG excitability and CGRP expression playing a role in its mechanisms of action. tONS may represent a promising non-invasive neuromodulation approach for the management of migraine in the future.
临床观察表明，经皮枕神经刺激（tONS）对偏头痛治疗有效。然而，其潜在机制尚不清楚。本研究采用啮齿动物模型来研究tONS对偏头痛相关疼痛的治疗效果，并探索潜在机制。
使用SD大鼠通过反复硬膜外注射炎性介质（IS）建立偏头痛模型。采用改良双侧电极进行无创tONS治疗。使用von-Frey细丝评估眶周机械阈值，并通过视频记录分析其他与疼痛相关的伤害性感受行为。通过免疫荧光和蛋白质免疫印迹分析测量三叉神经尾核（TNC）和/或导水管周围灰质（PAG）区域中c-Fos、突触素（Syp）和降钙素基因相关肽（CGRP）的表达。通过全细胞膜片钳记录检测偏头痛大鼠PAG中的兴奋性突触传递。
tONS治疗可部分逆转偏头痛大鼠反复注射IS引起的眶周机械阈值降低。tONS治疗后，包括探索、休息和单侧梳理在内的其他与疼痛相关的行为持续改善。IS建模后TNC和PAG区域被激活，tONS治疗后PAG中CGRP表达显著降低。tONS可抑制偏头痛大鼠PAG中增强的兴奋性突触传递。
我们的研究结果表明，tONS在治疗偏头痛方面具有治疗潜力，PAG兴奋性和CGRP表达在其作用机制中发挥作用。tONS可能代表未来一种有前景的偏头痛非侵入性神经调节方法。
