Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-05-12 DOI:10.1016/j.brainresbull.2025.111383

Tianying Li , Guanwen Lin , Tao Zhang , Yani Guo , Yongjin He , Jing Luan , Jin Wang , Dan Lyu , Yiqi Weng , Xin Jin

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引用次数: 0

Abstract

Background and aim

Neuropathic pain (NP), caused by nerve injury or dysfunction, poses a significant clinical challenge due to its limited response to conventional pharmacological treatments. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive neuromodulatory approach for NP management. This study aimed to evaluate the therapeutic efficacy of rTMS in alleviating NP induced by chronic constriction injury (CCI) in a mouse model and to investigate the underlying molecular mechanisms through transcriptomic profiling.

Procedures

Adult male mice underwent CCI surgery to induce NP and were randomly assigned to receive either rTMS (5 Hz or 10 Hz) or sham stimulation. rTMS was applied once daily for 14 consecutive days, beginning on postoperative day 7. Behavioral assessments—including paw withdrawal latency (PWL) and paw withdrawal threshold (PWT)—were conducted to evaluate thermal hyperalgesia and mechanical allodynia, respectively. Anxiety-like behaviors were assessed using the open field test (OFT) and elevated plus maze (EPM). At the end of the treatment period, brain tissues were harvested for RNA sequencing and differentially expressed genes (DEGs) were identified and analyzed.

Results and conclusion

rTMS at both 5 Hz and 10 Hz significantly improved PWL and PWT in CCI mice and reduced anxiety-like behaviors. Transcriptomic analysis revealed that CCI induced dysregulation of 66 genes, while rTMS partially normalized gene expression patterns. Functional enrichment analysis indicated significant involvement of pathways related to inflammatory responses, transporter activity, and ion channel regulation. These findings support the potential of rTMS as a multifaceted, non-invasive therapeutic strategy for neuropathic pain, with molecular mechanisms likely involving modulation of neuroinflammatory and neuroexcitatory pathways.

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重复经颅磁刺激改善慢性收缩损伤小鼠模型的慢性疼痛行为并调节脑转录组

背景和目的神经性疼痛（NP）是由神经损伤或功能障碍引起的，由于其对常规药物治疗的反应有限，给临床带来了重大挑战。重复经颅磁刺激（rTMS）已成为一种有前途的非侵入性神经调节方法来治疗NP。本研究旨在评价rTMS对小鼠慢性收缩损伤（CCI）所致NP的治疗效果，并通过转录组学分析探讨其潜在的分子机制。成年雄性小鼠接受CCI手术诱导NP，并被随机分配接受rTMS（5 Hz或10 Hz）或假刺激。rTMS从术后第7天开始，每天1次，连续14天。行为学评估——包括足爪退缩潜伏期（PWL）和足爪退缩阈值（PWT）——分别用于评估热痛觉过敏和机械异常性痛。焦虑样行为采用开阔场测试（OFT）和高架迷宫（EPM）进行评估。在治疗期结束时，采集脑组织进行RNA测序，并鉴定和分析差异表达基因（DEGs）。结果与结论5 Hz和10 Hz的rtms均能显著改善CCI小鼠的PWL和PWT，减少焦虑样行为。转录组学分析显示，CCI诱导了66个基因的失调，而rTMS使基因表达模式部分正常化。功能富集分析表明，与炎症反应、转运体活性和离子通道调节相关的途径显著参与。这些发现支持rTMS作为神经性疼痛的一种多面、无创治疗策略的潜力，其分子机制可能涉及神经炎症和神经兴奋通路的调节。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.