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Translational psychiatry. 2025 Jun 17;15(1):203. doi: 10.1038/s41398-025-03417-0 Q16.22025

Chronic postoperative pain induces contextual fear extinction dysfunction through hippocampal NMDAR/BDNF/TrkB signaling pathway in mice

慢性术后疼痛通过小鼠海马NMDAR/BDNF/TrkB信号通路诱导情境恐惧消退障碍 翻译改进

Jiawei Zhang  1  2, Xiaoting Zheng  3, Gaoyan Zhang  1  2, Zhikun Cheng  1  2, Yinuo Liu  1  2, Lei Zhang  1  2, Jiqian Zhang  1  2, Xuesheng Liu  4  5, Zhilai Yang  6  7

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作者单位

  • 1 Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China.
  • 2 Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui Province, China.
  • 3 Department of Anesthesiology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530007, China.
  • 4 Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China. liuxuesheng@ahmu.edu.cn.
  • 5 Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui Province, China. liuxuesheng@ahmu.edu.cn.
  • 6 Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China. yangzhilai@163.com.
  • 7 Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui Province, China. yangzhilai@163.com.

    • DOI: 10.1038/s41398-025-03417-0 PMID: 40527933

    摘要 中英对照阅读

    Post-traumatic stress disorder (PTSD) is a common disorder in clinical practice, characterized by various manifestations, with fear extinction dysfunction being a typical one. Postoperative persistent pain, a form of chronic pain following surgical procedures, significantly affects patients' quality of life. Clinical studies have demonstrated the comorbidity between chronic pain and PTSD; however, the molecular mechanisms underlying this comorbidity remai... ...点击完成人机验证后继续浏览

    创伤后应激障碍（PTSD）是临床实践中常见的疾病，其特征表现为各种症状，其中恐惧消退功能障碍是最典型的之一。术后持续性疼痛是一种手术后的慢性疼痛形式，显著影响患者的生活质量。临床研究表明，慢性疼痛和 PTSD 之间存在共病关系；然而，这种共病的分子机制尚不清楚。研究显示，脑源性神经营养因子（BDNF）和 N-甲基-D-天冬氨酸谷氨酸受体（NMDARs）在恐惧消退功能障碍中起关键作用。因此，我们建立了一个皮肤/肌肉切开和牵拉（SMIR）小鼠模型，以探讨海马区的 NMDARs 和 BDNF 信号通路在术后持续性疼痛后的恐惧消退中的作用。我们发现 SMIR 小鼠表现出情境恐惧消退功能障碍，可能是由于 NMDARs/ERK/CREB/BDNF 信号通路下调和海马区突触可塑性受损所致。海马注射 NMDARs 激动剂 NMDA 可促进恐惧消退学习和消退记忆的检索，激活 NMDARs/ERK/CREB/BDNF 信号通路，并恢复丢失的树突棘。同时在海马区给予 NMDA 和 TrkB 抑制剂 ANA-12 则促进了恐惧消退的学习过程而不增强消退记忆的检索，并重新诱导了树突棘损失。总之，我们得出结论，术后持续性疼痛通过下调 NMDARs/ERK/CREB/BDNF 信号通路而损害突触可塑性，从而导致情境恐惧消退功能障碍。这些发现可能部分解释了慢性疼痛和 PTSD 共病的机制。

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    期刊名：Translational psychiatry

    缩写：TRANSL PSYCHIAT

    ISSN：2158-3188

    e-ISSN：2158-3188

    IF/分区：6.2/Q1

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    Chronic postoperative pain induces contextual fear extinction dysfunction through hippocampal NMDAR/BDNF/TrkB signaling pathway in mice