The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception

The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception
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DOI:
10.1152/ajpgi.00501.2011
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发表时间:
2012-06-01
影响因子:
4.5
通讯作者:
Greenwood-Van Meerveld, Beverley
Greenwood-Van Meerveld, Beverley
中科院分区:
医学2区
文献类型:
--
作者:
Lee Tran;Wiskur, Brandt;Greenwood-Van Meerveld, Beverley

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Tran L,Wiskur B,Greenwood-Van Meerveld B.终纹前外侧床核在应激性伤害感受中的作用。美国生理学杂志胃肠和肝脏生理学302:G1301-G1309,2012年。首次发表于2012年4月5日; doi:10.1152/ajpgi.00501.2011。皮质酮(CORT)激活中央杏仁核(CeA)可通过促肾上腺皮质激素释放因子(CRF)依赖性机制诱导躯体和结肠超敏反应。然而,终纹床核(BNST),延长杏仁核的一部分,对伤害性感受的重要性仍然没有探索。在本研究中,我们测试的假设,刺激的CeA CORT诱导躯体和结肠超敏反应,通过激活的前外侧BNST(BNSTAL)。在动物的CeA或BNSTAL上植入CORT或胆固醇(CHOL)微丸。机械敏感性进行量化,使用电子冯弗雷细丝,和结肠伤害性通过量化内脏反应分级结直肠扩张。原位杂交用于测定BNSTAL中CRF、CRF 1和CRF 2受体的mRNA水平。在第二组中,动物双侧植入1)CORT或CHOL微丸至CeA上;和2)定位于BNSTAL的插管,以给予CRF 1受体拮抗剂(CP 376395)。与CHOL对照组相比,将CORT植入CeA而非BNSTAL的动物在BNST中表现出CRF mRNA表达增加和CRF 1与CRF 2受体比率增加,以及躯体和结肠超敏反应。向BNSTAL中输注CP 376395可抑制杏仁核CORT升高引起的躯体和结肠超敏反应。杏仁核CORT升高诱导的躯体和结肠超敏反应是通过BNSTAL中的CRF 1受体依赖性机制介导的。CeA通过涉及BNSTAL的下行通路在躯体和结肠伤害性感受中起关键作用。
Tran L, Wiskur B, Greenwood-Van Meerveld B. The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception. Am J Physiol Gastrointest Liver Physiol 302: G1301-G1309, 2012. First published April 5, 2012; doi:10.1152/ajpgi.00501.2011.-Activation of the central amygdala (CeA) by corticosterone (CORT) induces somatic and colonic hypersensitivity through corticotrophin-releasing factor (CRF)-dependent mechanisms. However, the importance of the bed nucleus of the stria terminalis (BNST), part of the extended amygdala, on nociception remains unexplored. In the present study, we test the hypothesis that stimulation of the CeA by CORT induces somatic and colonic hypersensitivity through activation of the anteriolateral BNST (BNSTAL). Animals were implanted with micropellets of CORT or cholesterol (CHOL) onto the CeA or the BNSTAL. Mechanical sensitivity was quantified using electronic von Frey filaments, and colonic nociception was measured by quantifying a visceromotor response to graded colorectal distension. In situ hybridization was used to determine mRNA levels for CRF, CRF1, and CRF2 receptors in the BNSTAL. In a second group, animals were implanted bilaterally with 1) CORT or CHOL micropellets onto the CeA; and 2) cannulas localized to the BNSTAL to administer a CRF1 receptor antagonist (CP376395). Animals implanted with CORT onto the CeA, but not the BNSTAL, exhibited increased expression of CRF mRNA and increased CRF1-to-CRF2 receptor ratio in the BNST, as well as somatic and colonic hypersensitivity compared with CHOL controls. Infusion of CP376395 into the BNSTAL inhibited somatic and colonic hypersensitivity in response to elevated amygdala CORT. Somatic and colonic hypersensitivity induced by elevated amygdala CORT is mediated via a CRF1 receptor-dependent mechanism in the BNSTAL. The CeA through a descending pathway involving the BNSTAL plays a pivotal role in somatic and colonic nociception.