Electroacupuncture reduces microglial hyperactivity and synaptic phagocytosis in the medial prefrontal cortex to treat chronic pain comorbid with anxiety and depression

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-08-23 DOI:10.1016/j.brainresbull.2025.111521

Wei Li , Weiqi Chang , Kaiyu Cui , Zuqi Shen , Xuan Yin , Shifen Xu

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引用次数: 0

Abstract

The role of dysfunctional microglial phagocytosis in the comorbidity of pain and affective disorders remains unclear. This study aimed to develop a potential therapeutic strategy targeting microglial phagocytosis. We established a mouse model of chronic constriction injury of the infraorbital nerve (CION) to induce pain and anxiety- and depressive-like behaviors simultaneously. Immunohistochemical analysis showed that CION led to increased density and aberrant morphology of microglia in the medial prefrontal cortex (mPFC), upregulation of lysosome-associated membrane protein 2 (LAMP2) and MER proto-oncogene tyrosine kinase (MERTK), and significant enhancement of phagocytosis of PSD-95-positive synaptic components by microglia. However, local injection of the microglia inhibitor minocycline into the mPFC markedly alleviated pain-induced anxiety-like behaviors. As a non-pharmacological intervention, electroacupuncture (EA) reduced the severity of pain-induced anxiety- and depressive-like behaviors, decreased the density of microglia and restored their morphology in the mPFC, and normalized MERTK expression levels. These results suggest that aberrant phagocytosis of excitatory synapses by microglia in the mPFC participates in regulating pain-induced anxiety-like behaviors, likely through MERTK. Pharmacological and non-pharmacological approaches (e.g., EA) targeting microglial phagocytosis in the mPFC may represent novel therapeutic strategies for chronic pain comorbid with anxiety and depression.

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电针减少内侧前额皮质小胶质细胞亢进和突触吞噬治疗伴焦虑和抑郁的慢性疼痛。

功能失调的小胶质细胞吞噬在疼痛和情感障碍合并症中的作用尚不清楚。本研究旨在开发一种针对小胶质细胞吞噬的潜在治疗策略。建立小鼠眶下神经慢性收缩损伤模型，同时诱导疼痛和焦虑、抑郁样行为。免疫组织化学分析显示，CION导致内侧前额叶皮层（mPFC）小胶质细胞密度增加和形态异常，溶酶体相关膜蛋白2 （LAMP2）和MER原癌基因酪氨酸激酶（MERTK）上调，小胶质细胞对psd -95阳性突触成分的吞噬能力显著增强。然而，局部注射小胶质细胞抑制剂米诺环素到mPFC显著减轻疼痛引起的焦虑样行为。作为一种非药物干预，电针（EA）降低了疼痛引起的焦虑和抑郁样行为的严重程度，降低了mPFC中小胶质细胞的密度并恢复了它们的形态，并使MERTK表达水平正常化。这些结果表明，mPFC中的小胶质细胞对兴奋性突触的异常吞噬可能通过MERTK参与调节疼痛诱导的焦虑样行为。针对mPFC中小胶质细胞吞噬的药物和非药物方法（例如，EA）可能代表了治疗慢性疼痛伴焦虑和抑郁的新策略。

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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.