The role of microglia in neuropathic pain: A systematic review of animal experiments

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-06-03 DOI:10.1016/j.brainresbull.2025.111410

Junyi Long , Guihua Tian , Ke He , Youxiang Su , Ziyao Wang , Liangqing Huang , Youmei Yao , Xinyi Li , Yi Lin

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引用次数: 0

Abstract

Background

Neuropathic pain develops from lesions or diseases that affect the peripheral or central somatosensory nervous system. External factors causing nervous system damage may induce neuropathic pain, which is often refractory and profoundly impairs patients’ quality of life and functional capacity.

Objective

This study aims to evaluate animal studies on neuropathic pain in the past three years to elucidate the mechanism of microglia in neuropathic pain and to provide a theoretical basis for clinical treatment.

Methods

Literature searches were conducted through seven databases, including Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Science and Technology Journal Database (VIPC), and SinoMed. The neuropathic pain model animals' pain indicators (thermal pain threshold, mechanical pain threshold), microglia-related findings, and related mechanism discoveries were extracted from the included studies.

Results

A total of 24 animal studies were included in this study. All studies showed that microglia exhibited an activated state in animal neuropathic pain models established by different methods. Twenty studies demonstrated that microglial activation exacerbates neuropathic pain by driving neuroinflammatory cascades. However, four studies confirmed that microglia could alleviate pain through the M2 phenotype and the release of endogenous opioid peptides.

Conclusion

The mediating effect of microglia on neuropathic pain is bidirectional. Pain-activated microglia do not necessarily exacerbate pain. Polarization toward the M2 phenotype or stimulation of endogenous opioid peptide release from microglia may attenuate pain. Overall, there are still many uncertainties about the mechanism of microglia in neuropathic pain. It is suggested to further study the neurobiological mechanism of this process to provide ideas for the design of future clinical trials.

Registration

PROSPERO (ID: CRD42024599437)

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小胶质细胞在神经性疼痛中的作用：动物实验的系统回顾

背景：神经性疼痛是由影响周围或中枢体感神经系统的病变或疾病引起的。引起神经系统损伤的外部因素可诱发神经性疼痛，这种疼痛往往是难治性的，严重影响患者的生活质量和功能能力。目的对近三年来神经性疼痛的动物研究进行评价，阐明小胶质细胞在神经性疼痛中的作用机制，为临床治疗提供理论依据。方法通过Web of Science、PubMed、EMBASE、中国知网（CNKI）、万方数据、中国科技期刊库（VIPC）、中国医学信息网（SinoMed）等7个数据库进行文献检索。从纳入的研究中提取神经性疼痛模型动物的疼痛指标（热痛阈、机械性痛阈）、小胶质细胞相关发现及相关机制发现。结果本研究共纳入24项动物实验。实验结果表明，在不同方法建立的动物神经性疼痛模型中，小胶质细胞均呈现激活状态。20项研究表明，小胶质细胞激活通过驱动神经炎症级联反应加剧神经性疼痛。然而，四项研究证实，小胶质细胞可以通过M2表型和内源性阿片肽的释放来减轻疼痛。结论小胶质细胞对神经性疼痛的介导作用是双向的。疼痛激活的小胶质细胞并不一定会加剧疼痛。向M2表型极化或刺激小胶质细胞内源性阿片肽释放可能减轻疼痛。总的来说，关于小胶质细胞在神经性疼痛中的作用机制仍有许多不确定性。建议进一步研究这一过程的神经生物学机制，为今后临床试验的设计提供思路。RegistrationPROSPERO （ID: CRD42024599437）

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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.