Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat.
Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat.
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DOI：
10.1016/j.neuropharm.2015.01.018
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发表时间：
2015-06
影响因子：
4.7
通讯作者：
Greenwood-Van Meerveld B
中科院分区：
文献类型：
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作者：
Johnson AC;Greenwood-Van Meerveld B
之前我们已经证明，杏仁核中央核（CeA）暴露于皮质酮（CORT）升高的环境中会诱导伤害性行为，这种行为会被糖皮质激素和/或矿皮质激素（GR/MR）受体拮抗剂逆转。在此，我们验证了一个假设，即在胆固醇（CHOL）植入的对照大鼠中，CeA中GR/MR的选择性敲低将通过促肾上腺皮质激素释放因子（CRF）介导的机制，复制杏仁核CORT升高所产生的伤害性行为。将CHOL或CORT微球立体放置于CeA背缘。在CeA中植入导管，以传递载体或针对GR或mr的反义或随机序列的寡脱氧核苷酸（ODN）。脏器运动行为反应量化了结肠膨胀时内脏的敏感性，而von Frey纤维评估了身体的敏感性。采用qRT-PCR检测受体表达。在植入CHOL的对照中，CeA中GR的敲低增加了结肠和体细胞敏感性，而CeA中MR的选择性敲低诱导结肠超敏而不影响体细胞敏感性。经GR或MR ASO处理的choll植入大鼠CeA中CRF表达增加，与cort植入大鼠中CRF表达增强相似。这是第一个证明降低CeA内的GR或MR都足以诱导内脏超敏反应，而仅在GR敲低后就会产生躯体超敏反应的研究。GR或MR的缺失与CRF表达的增加有关，这可能代表了cea介导的伤害性行为发展的共同机制。
Previously we demonstrated that exposure of the central nucleus of the amygdala (CeA) to elevated corticosterone (CORT) induces nociceptive behaviors that are reversed by glucocorticoid and/or mineralocorticoid (GR/MR) receptor antagonism. Here we test the hypothesis that in a cholesterol (CHOL)-implanted control rat, selective knockdown of GR/MR in the CeA would, via a corticotropin-releasing factor (CRF)-mediated mechanism, replicate the nociceptive behaviors produced by elevated amygdala CORT. Micropellets of CHOL or CORT were stereotaxically placed on the dorsal margin of the CeA. Cannulae were implanted into the CeA for the delivery of vehicle or oligodeoxynucleotides (ODN) of either antisense (ASO) or random sequences (RSO) targeting GR or MR. Visceromotor behavioral response quantified visceral sensitivity in response to colonic distension, while von Frey filaments assessed somatic sensitivity. Receptor expression was determined with qRT-PCR. In CHOL implanted controls, knockdown of GR in the CeA increased both colonic and somatic sensitivity, whereas selective knockdown of MR in the CeA induced colonic hypersensitivity without affecting somatic sensitivity. CRF expression in the CeA was increased in CHOL-implanted rats treated with GR or MR ASO and resembled the augmented CRF expression seen in the CORT-implanted rats. This is the first study to demonstrate that decreasing either GR or MR within the CeA is sufficient to induce visceral hypersensitivity whereas somatic hypersensitivity developed after only GR knockdown. The loss of either GR or MR was associated with an increased CRF expression, and may represent a common mechanism for the development of CeA-mediated nociceptive behaviors.