Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain,Journal of Neuroscience Research

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Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2021-05-06 , DOI: 10.1002/jnr.24846
Andrew H Cooper ₁ , Naomi S Hedden ₂ , Gregory Corder _{3,

4} , Sydney R Lamerand _{2,

5} , Renee R Donahue ₆ , Julio C Morales-Medina ₆ , Lindsay Selan ₂ , Pranav Prasoon ₂ , Bradley K Taylor ₂

Affiliation

Tissue injury induces a long-lasting latent sensitization (LS) of spinal nociceptive signaling that is kept in remission by an opposing µ-opioid receptor (MOR) constitutive activity. To test the hypothesis that supraspinal sites become engaged, we induced hindpaw inflammation, waited 3 weeks for mechanical hypersensitivity to resolve, and then injected the opioid receptor inhibitors naltrexone, CTOP or β-funaltrexamine subcutaneously, and/or into the cerebral ventricles. Intracerebroventricular injection of each inhibitor reinstated hypersensitivity and produced somatic signs of withdrawal, indicative of LS and endogenous opioid dependence, respectively. In naïve or sham controls, systemic naloxone (3 mg/kg) produced conditioned place aversion, and systemic naltrexone (3 mg/kg) increased Fos expression in the central nucleus of the amygdala (CeA). In LS animals tested 3 weeks after plantar incision, systemic naltrexone reinstated mechanical hypersensitivity and produced an even greater increase in Fos than in sham controls, particularly in the capsular subdivision of the right CeA. One third of Fos+ profiles co-expressed protein kinase C delta (PKCδ), and 35% of PKCδ neurons co-expressed tdTomato+ in Oprm1^Cre::tdTomato transgenic mice. CeA microinjection of naltrexone (1 µg) reinstated mechanical hypersensitivity only in male mice and did not produce signs of somatic withdrawal. Intra-CeA injection of the MOR-selective inhibitor CTAP (300 ng) reinstated hypersensitivity in both male and female mice. We conclude that MORs in the capsular subdivision of the right CeA prevent the transition from acute to chronic postoperative pain.

中文翻译：

杏仁核右中央核外侧和被膜部分的内源性 µ-阿片受体活性可预防慢性术后疼痛

组织损伤会导致脊髓伤害性信号传导的持久潜在致敏 (LS)，该信号通过相反的 μ-阿片受体 (MOR) 组成活性保持缓解状态。为了验证脊柱上部位参与的假设，我们诱发了后爪炎症，等待 3 周机械超敏反应消退，然后皮下注射阿片受体抑制剂纳曲酮、CTOP 或 β-呋纳曲胺，和/或进入脑室。脑室内注射每种抑制剂可恢复超敏反应并产生躯体戒断症状，分别表明 LS 和内源性阿片类药物依赖性。在幼稚或假对照中，全身纳洛酮 (3 mg/kg) 产生条件性位置厌恶，全身纳曲酮 (3 mg/kg) 增加杏仁核中央核 (CeA) 中的 Fos 表达。在足底切开 3 周后测试的 LS 动物中，全身性纳曲酮恢复了机械超敏反应，并产生了比假对照组更大的 Fos 增加，特别是在右侧 CeA 的囊状细分中。三分之一的 Fos+ 配置文件共表达蛋白激酶 C δ (PKCδ)，35% 的 PKCδ 神经元共表达 tdTomato+Oprm1 ^Cre :: tdTomato 转基因小鼠。纳曲酮 (1 µg) 的 CeA 显微注射仅在雄性小鼠中恢复了机械超敏反应，并且没有产生躯体戒断迹象。CeA 内注射 MOR 选择性抑制剂 CTAP (300 ng) 可恢复雄性和雌性小鼠的超敏反应。我们得出结论，右侧 CeA 的囊状细分中的 MOR 可防止从急性术后疼痛转变为慢性术后疼痛。

更新日期：2021-05-06

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