经皮耳迷走神经刺激经5 -羟色胺能通路对小鼠部分坐骨神经结扎所致神经性疼痛的镇痛作用。

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Hyunjin Shin, Seunghwan Choi, Geehoon Chung, Sun Kwang Kim
{"title":"经皮耳迷走神经刺激经5 -羟色胺能通路对小鼠部分坐骨神经结扎所致神经性疼痛的镇痛作用。","authors":"Hyunjin Shin, Seunghwan Choi, Geehoon Chung, Sun Kwang Kim","doi":"10.1186/s13041-025-01246-2","DOIUrl":null,"url":null,"abstract":"<p><p>Current treatments for neuropathic pain often provide limited relief and are associated with significant side effects. Transcutaneous auricular vagus nerve stimulation (taVNS) shows promise as a non-pharmacological analgesic approach; however, its optimal therapeutic configuration and underlying brain mechanisms remain incompletely understood. This study investigated the analgesic effects of taVNS on neuropathic pain in a mouse model induced by partial sciatic nerve ligation (PSL), exploring mechanisms and optimizing configurations. PSL-induced neuropathic pain in mice, characterized by mechanical allodynia, was significantly alleviated by taVNS. The most robust analgesic effects were observed with multiple bilateral taVNS sessions, administered once daily for three consecutive days, with effects persisting for at least 48 h post-stimulation. Immunohistochemical analysis of c-Fos expression revealed that taVNS increased neural activity in the dorsal raphe nucleus (DRN), a key source of serotonin, while simultaneously reducing activity in the central amygdala (CeA), a region critical for pain processing and affective responses. Further experiments demonstrated that the analgesic effects of taVNS were abolished by systemic administration of p-chlorophenylalanine, an inhibitor of serotonin synthesis. These findings underscore the critical role of serotonin signaling in mediating taVNS-induced analgesia for neuropathic pain. The study also highlights the importance of stimulation parameters, identifying a multiple bilateral configuration as particularly effective. Our results suggest that taVNS, potentially acting via the DRN-serotonergic system to modulate limbic structures like the CeA, holds significant potential as a non-pharmacological therapeutic option for managing neuropathic pain.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"73"},"PeriodicalIF":2.9000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466006/pdf/","citationCount":"0","resultStr":"{\"title\":\"Analgesic effects of transcutaneous auricular vagus nerve stimulation on partial sciatic nerve ligation-induced neuropathic pain in mice via serotonergic pathways.\",\"authors\":\"Hyunjin Shin, Seunghwan Choi, Geehoon Chung, Sun Kwang Kim\",\"doi\":\"10.1186/s13041-025-01246-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Current treatments for neuropathic pain often provide limited relief and are associated with significant side effects. Transcutaneous auricular vagus nerve stimulation (taVNS) shows promise as a non-pharmacological analgesic approach; however, its optimal therapeutic configuration and underlying brain mechanisms remain incompletely understood. This study investigated the analgesic effects of taVNS on neuropathic pain in a mouse model induced by partial sciatic nerve ligation (PSL), exploring mechanisms and optimizing configurations. PSL-induced neuropathic pain in mice, characterized by mechanical allodynia, was significantly alleviated by taVNS. The most robust analgesic effects were observed with multiple bilateral taVNS sessions, administered once daily for three consecutive days, with effects persisting for at least 48 h post-stimulation. Immunohistochemical analysis of c-Fos expression revealed that taVNS increased neural activity in the dorsal raphe nucleus (DRN), a key source of serotonin, while simultaneously reducing activity in the central amygdala (CeA), a region critical for pain processing and affective responses. Further experiments demonstrated that the analgesic effects of taVNS were abolished by systemic administration of p-chlorophenylalanine, an inhibitor of serotonin synthesis. These findings underscore the critical role of serotonin signaling in mediating taVNS-induced analgesia for neuropathic pain. The study also highlights the importance of stimulation parameters, identifying a multiple bilateral configuration as particularly effective. Our results suggest that taVNS, potentially acting via the DRN-serotonergic system to modulate limbic structures like the CeA, holds significant potential as a non-pharmacological therapeutic option for managing neuropathic pain.</p>\",\"PeriodicalId\":18851,\"journal\":{\"name\":\"Molecular Brain\",\"volume\":\"18 1\",\"pages\":\"73\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466006/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Brain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13041-025-01246-2\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Brain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13041-025-01246-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

目前对神经性疼痛的治疗通常提供有限的缓解,并伴有明显的副作用。经皮耳迷走神经刺激(taVNS)显示出作为一种非药物镇痛方法的希望;然而,其最佳的治疗配置和潜在的大脑机制仍然不完全清楚。本研究探讨taVNS对部分坐骨神经结扎(PSL)小鼠神经性疼痛的镇痛作用,探讨其作用机制和优化配置。psl诱导的小鼠神经性疼痛,以机械异常性疼痛为特征,taVNS显著减轻。在多次双侧taVNS治疗中观察到最强大的镇痛效果,每天一次,连续三天,刺激后效果持续至少48小时。c-Fos表达的免疫组织化学分析显示,taVNS增加了中隔背核(DRN)的神经活性,DRN是血清素的主要来源,同时降低了中央杏仁核(CeA)的活性,而中央杏仁核是疼痛加工和情感反应的关键区域。进一步的实验表明,全身给药对氯苯丙氨酸(一种5 -羟色胺合成抑制剂)可以消除taVNS的镇痛作用。这些发现强调了血清素信号在介导tavns诱导的神经性疼痛镇痛中的关键作用。该研究还强调了增产参数的重要性,确定了多个双侧配置特别有效。我们的研究结果表明,taVNS可能通过drn - 5 -羟色胺能系统调节像CeA这样的边缘结构,作为治疗神经性疼痛的非药物治疗选择具有重大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analgesic effects of transcutaneous auricular vagus nerve stimulation on partial sciatic nerve ligation-induced neuropathic pain in mice via serotonergic pathways.

Current treatments for neuropathic pain often provide limited relief and are associated with significant side effects. Transcutaneous auricular vagus nerve stimulation (taVNS) shows promise as a non-pharmacological analgesic approach; however, its optimal therapeutic configuration and underlying brain mechanisms remain incompletely understood. This study investigated the analgesic effects of taVNS on neuropathic pain in a mouse model induced by partial sciatic nerve ligation (PSL), exploring mechanisms and optimizing configurations. PSL-induced neuropathic pain in mice, characterized by mechanical allodynia, was significantly alleviated by taVNS. The most robust analgesic effects were observed with multiple bilateral taVNS sessions, administered once daily for three consecutive days, with effects persisting for at least 48 h post-stimulation. Immunohistochemical analysis of c-Fos expression revealed that taVNS increased neural activity in the dorsal raphe nucleus (DRN), a key source of serotonin, while simultaneously reducing activity in the central amygdala (CeA), a region critical for pain processing and affective responses. Further experiments demonstrated that the analgesic effects of taVNS were abolished by systemic administration of p-chlorophenylalanine, an inhibitor of serotonin synthesis. These findings underscore the critical role of serotonin signaling in mediating taVNS-induced analgesia for neuropathic pain. The study also highlights the importance of stimulation parameters, identifying a multiple bilateral configuration as particularly effective. Our results suggest that taVNS, potentially acting via the DRN-serotonergic system to modulate limbic structures like the CeA, holds significant potential as a non-pharmacological therapeutic option for managing neuropathic pain.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信