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

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.