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PGE2增强了Orai1介导的进入,有助于外周敏感化

Dongyu Wei¹, Hareram Birla², Yannong Dou¹

¹Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102.

The Journal of neuroscience : the official journal of the Society for Neuroscience

|November 12, 2023

概括

在背部根系神经元中,Orai1介导的存储运行通道 (SOC) 功能在炎症性疼痛期间得到增强. 删除Orai1可以减少疼痛过敏和前列腺素E2 (PGE2) 诱导的敏感性,这表明Orai1是治疗点.

科学领域:

神经科学是一个神经科学.
疼痛研究疼痛研究
分子生物学分子生物学

背景情况:

周边敏感化是慢性疼痛病原体的关键,但参与的分子尚未完全理解.
储存运行的通道 (SOCs) 存在于背部根结节 (DRG) 神经元中,但它们在炎症性疼痛中的作用尚不清楚.

研究的目的:

研究SOCs的一个组成部分Orai1在外周敏感和炎症性疼痛中的作用.
阐明前列腺素E2 (PGE2) 在DRG神经元中调节Orai1功能的机制.

主要方法:

使用了全局和有条件的Orai1淘汰赛小鼠模型.
使用完整的弗洛恩德辅助剂 (CFA) 和胡卜素诱导的炎症性疼痛.
在DRG神经元上进行成像和补丁记录.
研究了PGE2,EP1受体对抗剂/激动剂和下游信号抑制剂 (Gq/11,PKC,ERK) 的作用.

主要成果:

在雄性和雌性小鼠中,Orai1删除减弱了CFA诱导的疼痛过敏.
从炎症野生型小鼠的DRG神经元中增强了SOC功能,但不是Orai1淘汰赛小鼠.
在Orai1淘汰赛小鼠中,PGE2诱导的神经元过敏和疼痛过敏性降低了.
在WT中通过EP1受体和下游信号 (Gq/11,PKC,ERK) 进行PGE2增强的SOC输入 (SOCE),但不是Orai1KO神经元.

结论:

Orai1在潜在的炎症性疼痛的外周敏感化中发挥着重要作用.
通过EP1介导的信号级联,PGE2增强DRG神经元中的SOCE.
Orai1代表了一种潜在的治疗点,用于管理病理性疼痛状况.

关键词:

EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 EP1 这里是Orai1 .在PGE2的基础上,PGE2 背部根结节神经元神经元神经元在商店经营的通道.

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