CGRP blockers in migraine therapy: where do they act?
CGRP blockers in migraine therapy: where do they act?
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DOI：
10.1038/bjp.2008.346
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发表时间：
2008-12-01
影响因子：
7.3
通讯作者：
Edvinsson, L.
中科院分区：
文献类型：
--
作者：
Edvinsson, L.
降钙素基因相关肽（CGRP）在整个CNS和外周神经系统中表达，与血管舒张、伤害感受、运动功能、分泌和嗅觉的控制一致。α CGRP主要位于脊髓和三叉神经节的初级传入C和Ad纤维中。三叉神经的激活导致CGRP的逆向释放，通过CGRP 1受体起作用。CGRP 1受体拮抗剂减少三叉神经血管通路中多个部位的信号传导，尤其是血脑屏障内。与CGRP机制相互作用的其他方式似乎限制了CGRP在循环中与特异性CGRP抗体或CGRP结合RNA-Spiegelmer的可用性。任何一种方式都可以减少神经源性炎症并减弱三叉神经血管通路内的信号传导。特异性CGRP受体阻断剂已被证明可降低释放的CGRP的作用并中止急性偏头痛发作。减少可用CGRP的新方法受到血脑屏障的限制;其用途可能更多地是作为偏头痛的预防而不是急性治疗。
Calcitonin gene-related peptide (CGRP) is expressed throughout the CNS and peripheral nervous system, consistent with control of vasodilatation, nociception, motor function, secretion and olfaction. alpha CGRP is prominently localized in primary afferent C and Ad fibres of spinal and trigeminal ganglia. Activation of the trigeminal nerve results in antidromic release of CGRP, acting through a CGRP1 receptor. Antagonists of CGRP1 receptors reduce signalling in the trigeminovascular pathway at multiple sites, putatively inside the blood-brain barrier. Other ways of interacting with CGRP mechanisms have appeared limiting the availability of CGRP in the circulation with a specific CGRP antibody or with a CGRP-binding RNA-Spiegelmer. Either way reduces neurogenic inflammation and attenuates signalling within the trigeminovascular pathway. Specific CGRP receptor blockade has been shown to reduce the effect of released CGRP and to abort acute migraine attacks. The novel approach of reducing available CGRP is limited by the blood-brain barrier; its usefulness may be more as prophylaxis rather than as acute treatment of migraine.