妊娠通过抑制小胶质细胞和上调妊娠晚期小鼠前扣带回皮层中的δ-阿片受体来改善神经性疼痛。

IF 2.8 3区 医学 Q2 ANESTHESIOLOGY
Atsushi Sawada, Michiaki Yamakage
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引用次数: 0

摘要

目的:妊娠诱导镇痛在妊娠晚期出现,但其机制尚不清楚。前扣带回皮层(ACC)在神经性疼痛的发病机制中起着关键作用。作者假设,妊娠诱导的镇痛可抑制小胶质细胞的激活和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体的表达,并上调妊娠晚期小鼠 ACC 中的阿片受体,从而改善神经病理性疼痛:方法:通过坐骨神经部分结扎术(PSNL)诱导非妊娠(NP)或妊娠(P)C57BL/6JJmsSlc雌性小鼠产生神经性疼痛。痛觉反应通过机械异感进行评估,ACC 中小胶质细胞的激活通过免疫组化进行评估。免疫印迹法评估了 ACC 中磷酸化 AMPA 受体和阿片受体的表达:结果:在von Frey反射测试中,NP-PSNL处理的小鼠在实验第9天的50%爪抽离阈值低于NP-Naïve小鼠。NP-Naïve小鼠、NP-Sham小鼠、P-Sham小鼠和P-PSNL处理小鼠的50%爪抽离阈值没有差异。与 NP-Sham 小鼠相比,NP-PSNL 治疗小鼠 ACC 中的小胶质细胞数量明显增加。免疫印迹显示,与 NP-Sham 小鼠相比,NP-PSNL 处理的小鼠 AMPA 受体亚基 GluR1 在 Ser831 处的磷酸化表达明显增加。免疫印迹还显示,与 NP-Sham 小鼠相比,P-Sham 和 P-PSNL 处理的小鼠 ACC 中的δ-阿片受体明显增加:结论:妊娠诱导镇痛可抑制小胶质细胞的活化和磷酸化AMPA受体亚基GluR1在Ser831处的表达,并上调妊娠晚期小鼠ACC中的δ-阿片受体,从而改善神经病理性疼痛。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Pregnancy ameliorates neuropathic pain through suppression of microglia and upregulation of the δ-opioid receptor in the anterior cingulate cortex in late-pregnant mice.

Pregnancy ameliorates neuropathic pain through suppression of microglia and upregulation of the δ-opioid receptor in the anterior cingulate cortex in late-pregnant mice.

Purpose: Pregnancy-induced analgesia develops in late pregnancy, but its mechanisms are unclear. The anterior cingulate cortex (ACC) plays a key role in the pathogenesis of neuropathic pain. The authors hypothesized that pregnancy-induced analgesia ameliorates neuropathic pain by suppressing activation of microglia and the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and by upregulating opioid receptors in the ACC in late-pregnant mice.

Methods: Neuropathic pain was induced in non-pregnant (NP) or pregnant (P) C57BL/6JJmsSlc female mice by partial sciatic nerve ligation (PSNL). The nociceptive response was evaluated by mechanical allodynia and activation of microglia in the ACC was evaluated by immunohistochemistry. The expressions of phosphorylated AMPA receptors and opioid receptors in the ACC were evaluated by immunoblotting.

Results: In von Frey reflex tests, NP-PSNL-treated mice showed a lower 50% paw-withdrawal threshold than NP-Naïve mice on experimental day 9. No difference in 50% paw-withdrawal threshold was found among the NP-Naïve, NP-Sham, P-Sham, and P-PSNL-treated mice. The number of microglia in the ACC was significantly increased in NP-PSNL-treated mice compared to NP-Sham mice. Immunoblotting showed significantly increased expression of phosphorylated AMPA receptor subunit GluR1 at Ser831 in NP-PSNL-treated mice compared to NP-Sham mice. Immunoblotting also showed significantly increased δ-opioid receptor in the ACC in P-Sham and P-PSNL-treated mice compared to NP-Sham mice.

Conclusion: Pregnancy-induced analgesia ameliorated neuropathic pain by suppressing activation of microglia and the expression of phosphorylated AMPA receptor subunit GluR1 at Ser831, and by upregulation of the δ-opioid receptor in the ACC in late-pregnant mice.

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来源期刊
Journal of Anesthesia
Journal of Anesthesia 医学-麻醉学
CiteScore
5.30
自引率
7.10%
发文量
112
审稿时长
3-8 weeks
期刊介绍: The Journal of Anesthesia is the official journal of the Japanese Society of Anesthesiologists. This journal publishes original articles, review articles, special articles, clinical reports, short communications, letters to the editor, and book and multimedia reviews. The editors welcome the submission of manuscripts devoted to anesthesia and related topics from any country of the world. Membership in the Society is not a prerequisite. The Journal of Anesthesia (JA) welcomes case reports that show unique cases in perioperative medicine, intensive care, emergency medicine, and pain management.
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