VA Medical Center, Oklahoma City, OK 73104, USA.
Am J Physiol Gastrointest Liver Physiol. 2012 Jun 1;302(11):G1301-9. doi: 10.1152/ajpgi.00501.2011. Epub 2012 Apr 5.
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 (BNST(AL)). Animals were implanted with micropellets of CORT or cholesterol (CHOL) onto the CeA or the BNST(AL). 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, CRF(1), and CRF(2) receptors in the BNST(AL). In a second group, animals were implanted bilaterally with 1) CORT or CHOL micropellets onto the CeA; and 2) cannulas localized to the BNST(AL) to administer a CRF(1) receptor antagonist (CP376395). Animals implanted with CORT onto the CeA, but not the BNST(AL), exhibited increased expression of CRF mRNA and increased CRF(1)-to-CRF(2) receptor ratio in the BNST, as well as somatic and colonic hypersensitivity compared with CHOL controls. Infusion of CP376395 into the BNST(AL) inhibited somatic and colonic hypersensitivity in response to elevated amygdala CORT. Somatic and colonic hypersensitivity induced by elevated amygdala CORT is mediated via a CRF(1) receptor-dependent mechanism in the BNST(AL). The CeA through a descending pathway involving the BNST(AL) plays a pivotal role in somatic and colonic nociception.
中央杏仁核（CeA）的激活通过促肾上腺皮质激素释放因子（CRF）依赖机制诱导躯体和结肠过敏。然而，延伸杏仁核的一部分终纹床核（BNST）对疼痛感知的重要性仍未被探索。在本研究中，我们假设通过刺激 CeA 的 CORT 诱导躯体和结肠过敏，通过激活前外侧 BNST（BNST（AL））来实现。动物被植入 CORT 或胆固醇（CHOL）微球到 CeA 或 BNST（AL）。使用电子冯弗雷尔丝定量机械敏感性，通过量化对分级结直肠扩张的内脏运动反应来测量结肠疼痛感知。原位杂交用于确定 BNST（AL）中 CRF、CRF（1）和 CRF（2）受体的 mRNA 水平。在第二组中，动物被双侧植入 1）CORT 或 CHOL 微球到 CeA；和 2）定位到 BNST（AL）的套管以给予 CRF（1）受体拮抗剂（CP376395）。将 CORT 植入 CeA 的动物，但不是 BNST（AL），表现出 CRF mRNA 的表达增加和 BNST 中 CRF（1）到 CRF（2）受体比率增加，以及与 CHOL 对照相比的躯体和结肠过敏。将 CP376395 输注到 BNST（AL）抑制了对升高的杏仁核 CORT 的躯体和结肠过敏。通过升高的杏仁核 CORT 诱导的躯体和结肠过敏是通过 BNST（AL）中的 CRF（1）受体依赖性机制介导的。通过涉及 BNST（AL）的下行途径，CeA 在躯体和结肠疼痛感知中起着关键作用。
