Johnson A C, Tran L, Greenwood-Van Meerveld B
Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
1] Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA [2] Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA [3] VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
Transl Psychiatry. 2015 Mar 3;5(3):e517. doi: 10.1038/tp.2015.16.
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.
慢性应激通过一种未知机制加剧胃肠道伤害感受。杏仁核是参与对应激的自主神经和神经内分泌反应的关键核团。本研究的目的是检验以下假设：中央杏仁核（CeA）长期暴露于应激或应激激素皮质醇（大鼠中为皮质酮）会诱导CeA内促肾上腺皮质激素释放因子（CRF）介导的伤害感受行为。我们通过反义寡脱氧核苷酸（ASO）在动物中选择性敲低CeA中的CRF，这些动物植入了靶向、立体定位放置的皮质酮（CORT）微丸或经历了反复避水应激（WAS）。在评估对结肠扩张的内脏超敏反应和机械性躯体退缩阈值的同时，分析CeA中的CRF表达。在植入CORT微丸后7天或28天或经历7天WAS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。在两种模型中，向CeA内注入CRF ASO均可降低CRF表达并减轻内脏和躯体超敏反应。我们的研究为CeA内一种特定的由CRF介导的机制提供了重要证据，该机制调节应激诱导的内脏和躯体伤害感受。
