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术后疼痛小鼠展现出年龄差异性的脊髓小胶质细胞激活与抑制性突触丢失(英文)

王嘉宁^1,2, 申宇^1,2, 王士豪^1,2,3, 廖萍^1,2, 蒋若天^1,2,*

¹四川大学华西医院麻醉科，成都 610017；²四川大学华西医院麻醉转化医学国家地方联合工程研究中心，麻醉与危重症研究室，成都 610017；³四川大学华西临床医学院，成都 610017

摘要

持续性术后疼痛是当前临床面临的一个重要问题，尤其在老年人群中更为突出。随着人口老龄化的加剧，老年患者在手术人群中的比例不断上升。尽管年龄被认为是疼痛的已知危险因素之一，但导致老年人发生慢性术后疼痛的具体机制仍不清楚。本研究旨在探讨衰老对术后疼痛缓解进展的影响，并阐明脊髓背角小胶质细胞激活与突触重塑在此过程中的作用。在年轻(3 月龄)和老年(18 月龄)雌性与雄性小鼠中用标准化的足底切口模型来模拟术后疼痛状况，通过von Frey 和Hargreaves试验评估术后不同时间点的机械和热超敏反应，用免疫荧光染色以及Imaris 三维形态重建检测脊髓背角中小胶质细胞的激活情况及抑制性/兴奋性突触的密度变化。结果显示，术后第3 天，年轻与老年小鼠均表现出术侧足底疼痛阈值下降，并伴有脊髓背角小胶质细胞激活；在术后第7 天，年轻小鼠疼痛阈值基本恢复至基线水平，脊髓背角小胶质细胞术侧与对侧相比无明显激活，然而老年小鼠则仍表现为疼痛阈值降低、小胶质细胞持续激活及抑制性突触显著丢失，兴奋性突触密度没有明显变化。上述年龄相关的变化在雌性与雄性老年鼠中均存在，没有与性别相关的差异。以上研究结果提示，衰老与持续的术后疼痛有关，且术后疼痛与小胶质细胞激活和抑制性突触丢失有关。这些研究结果加深了对年龄相关疼痛易感性的理解，并为开发更有效、有针对性且适用于老年患者的治疗策略提供了理论依据，以预防或缓解老年患者的持续性术后疼痛。

关键词： 切口痛; 衰老; 脊髓背角; 小胶质细胞; 抑制性突触

Mice with postsurgical pain exhibit age-dependent spinal microglial activation and inhibitory synapse loss

WANG Jia-Ning^1,2, SHEN Yu^1,2, WANG Shi-Hao^1,2,3, LIAO Ping^1,2, JIANG Ruo-Tian^1,2,*

¹Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610017, China；²Laboratory of Anesthesia and Critical Care Medicine, Research Center of Anesthesiology, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610017, China；³West China School of Medicine, Sichuan University, Chengdu 610017, China

Abstract

Persistent postsurgical pain is a major clinical concern, especially in the aging population, who represent a growing proportion of surgical patients. Although age is a known pain risk factor, the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood. This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn. A plantar incision model in young (3- month-old) and aged (18-month-old) male and female mice was used to mimic postoperative pain conditions. Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests. Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software. On postoperative day (POD) 3, both age groups exhibited reduced pain thresholds on the ipsilateral side, along with microglial activation in the dorsal horn. On POD 7, pain thresholds in young mice had returned to baseline with no significant microglial activation, while aged mice showed sustained reduction in pain thresholds, continuous microglial activation, and significant loss of inhibitory synapses without detectable changes in excitatory synapse density. These findings are consistent across both sexes, with no sex-related differences. Collectively, these results suggest that aging is associated with persistent postoperative pain, which correlates with microglial activation and inhibitory synapse loss. These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective, targeted, and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.

Key words: incisional pain; aging; spinal dorsal horn; microglia; inhibitory synapses

收稿日期：　　录用日期：

通讯作者：蒋若天　　E-mail:

DOI: 10.13294/j.aps.2026.0005

引用本文：

王嘉宁, 申宇, 王士豪, 廖萍, 蒋若天. 术后疼痛小鼠展现出年龄差异性的脊髓小胶质细胞激活与抑制性突触丢失(英文)[J]. 生理学报 2026; 78 (1): 182-194.

WANG Jia-Ning, SHEN Yu, WANG Shi-Hao, LIAO Ping, JIANG Ruo-Tian. Mice with postsurgical pain exhibit age-dependent spinal microglial activation and inhibitory synapse loss. Acta Physiol Sin 2026; 78 (1): 182-194