Transcutaneous occipital nerve stimulation alleviated migraine related pain by regulating synaptic plasticity and CGRP expression in the periaqueductal gray of male rats.

IF 7.3 1区 医学 Q1 CLINICAL NEUROLOGY
Yinglu Liu, Shengli Guo, Yang Li, Jingrui Mao, Xiaoxue Lin, Ruozhuo Liu, Dengfa Zhao, Zhao Dong, Shengyuan Yu, Xun Han
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

经皮枕神经刺激通过调节雄性大鼠导水管周围灰质突触可塑性和CGRP表达减轻偏头痛相关疼痛。
背景:临床观察表明经皮枕神经刺激(tONS)治疗偏头痛是有效的。然而,人们对其潜在机制知之甚少。本研究采用啮齿类动物模型,研究ton对偏头痛相关疼痛的治疗作用,并探讨其可能的机制。方法:采用硬膜外反复灌注炎症汤(IS)建立SD大鼠偏头痛模型。改良的双侧电极无创附着用于治疗ton。采用von-Frey纤维评估眶周力学阈值,并通过录像分析其他与疼痛相关的伤害性行为。免疫荧光和western blot检测三叉神经尾核(TNC)和/或导尿管周围灰质(PAG)区c-Fos、突触素(Syp)和降钙素基因相关肽(CGRP)的表达。采用全细胞膜片钳法检测偏头痛大鼠PAG的兴奋性突触传递。结果:反复灌胃IS引起的大鼠眶周力学阈值降低可部分逆转。其他与疼痛相关的行为,包括探索、休息和单侧梳理,在ton治疗后持续改善。IS建模后,大鼠的TNC和PAG区被激活,tONS处理后PAG中CGRP的表达明显降低。多酚可抑制偏头痛大鼠PAG兴奋性突触传递的增强。结论:tONS具有治疗偏头痛的作用潜力,其作用机制可能与PAG兴奋性和CGRP表达有关。tONS可能代表了一种有前途的非侵入性神经调节方法来管理偏头痛在未来。
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来源期刊
Journal of Headache and Pain
Journal of Headache and Pain 医学-临床神经学
CiteScore
11.80
自引率
13.50%
发文量
143
审稿时长
6-12 weeks
期刊介绍: The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data. With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.
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