降钙素基因相关肽
偏头痛
医学
药理学
环磷酸腺苷
神经科学
苏马曲普坦
先兆偏头痛
受体
内分泌学
内科学
光环
神经肽
心理学
兴奋剂
作者
Thien Phu,Christina Deligianni,Sarkhan Amirguliyev,Josefin Snellman,Cristina López López,Mohammad Al‐Mahdi Al‐Karagholi,Song Guo,Anne Luise Haulund Vollesen
出处
期刊:Brain
[Oxford University Press]
日期:2023-08-04
卷期号:146 (12): 5224-5234
被引量:5
标识
DOI:10.1093/brain/awad261
摘要
There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine.
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