Knockdown of corticotropin-releasing factor in the central amygdala reverses persistent viscerosomatic hyperalgesia.
Knockdown of corticotropin-releasing factor in the central amygdala reverses persistent viscerosomatic hyperalgesia.
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DOI：
10.1038/tp.2015.16
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发表时间：
2015-03-03
影响因子：
6.8
通讯作者：
Greenwood-Van Meerveld B
中科院分区：
文献类型：
--
作者：
Johnson AC;Tran L;Greenwood-Van Meerveld B
慢性压力通过未知机制加剧胃肠道伤害感受。杏仁核是参与自主神经和神经内分泌应激反应的关键核。本研究的目的是检验这样的假设：杏仁核中央 (CeA) 长时间暴露于压力或应激激素皮质醇（或大鼠中的皮质酮）会诱发由 CeA 内促肾上腺皮质激素释放因子 (CRF) 介导的伤害性行为。我们通过定向立体定位皮质酮 (CORT) 微丸或反复回避水应激 (WAS) 后的动物体内，通过反义寡脱氧核苷酸 (ASO) 选择性地敲低 CeA 中的 CRF。分析 CeA 中的 CRF 表达，同时评估内脏对结肠扩张和机械性躯体退缩阈值的过敏性。在 CORT 微丸植入后 7 或 28 天或 WAS 7 天后对反应进行表征。 CeA 暴露于升高的 CORT 或 WAS 会增加 CRF 表达并增强内脏和躯体敏感性。将 CRF ASO 注入 CeA 后，两种模型中的 CRF 表达均降低，内脏和躯体过敏性减弱。我们的研究为 CRF 介导的机制提供了重要证据，特别是在 CeA 内调节应激诱导的内脏和躯体伤害感受。
Gastrointestinal nociception is exacerbated by chronic stress through an unknown mechanism. The amygdala is a key nucleus involved in the autonomic and neuroendocrine responses to stress. The goal of this study was to test the hypothesis that prolonged exposure of the central amygdala (CeA) to stress or the stress hormone cortisol (or corticosterone in rats) induces nociceptive behaviors mediated by corticotropin-releasing factor (CRF) within the CeA. We selectively knocked down CRF in the CeA via antisense oligodeoxynucleotides (ASO) in animals with targeted, stereotaxically placed corticosterone (CORT) micropellets or following repeated water avoidance stress (WAS). CRF expression in the CeA was analyzed concurrently with the assessment of visceral hypersensitivity to colonic distension and mechanical somatic withdrawal threshold. The responses were characterized at 7 or 28 days post implantation of the CORT micropellet or following 7 days of WAS. Exposure of the CeA to elevated CORT or WAS increased CRF expression and heightened visceral and somatic sensitivity. Infusion of CRF ASO into the CeA decreased CRF expression and attenuated visceral and somatic hypersensitivity in both models. Our study provides important evidence for a CRF-mediated mechanism specifically within the CeA that regulates stress-induced visceral and somatic nociception.
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影响因子：
2.5
作者：
Marchant, Nathan J.;Densmore, Valerie S.;Osborne, Peregrine B.
通讯作者：
Osborne, Peregrine B.
DOI：
10.1152/ajpgi.00507.2007
发表时间：
2008-04-01
影响因子：
4.5
作者：
Larauche, Muriel;Bradesi, Sylvie;McRoberts, James A.
通讯作者：
McRoberts, James A.
影响因子：
2.7
作者：
Myers, Brent;Dittmeyer, Kale;Greenwood-Van Meerveld, Beverley
通讯作者：
Greenwood-Van Meerveld, Beverley
影响因子：
2.9
作者：
Greenwood-Van Meerveld, B;Gibson, M;Myers, D
通讯作者：
Myers, D
影响因子：
7.6
作者：
Lee Tran;Schulkin, Jay;Greenwood-Van Meerveld, Beverley
通讯作者：
Greenwood-Van Meerveld, Beverley