Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
Neurology. 2010 Oct 26;75(17):1520-6. doi: 10.1212/WNL.0b013e3181f9626a.
Calcitonin gene-related peptide (CGRP) plays a fundamental role in the pathophysiology of neurovascular headaches. CGRP infusion causes headache and dilation of cranial vessels. However, it is unknown to what extent CGRP-induced vasodilation contributes to immediate head pain and whether the migraine-specific abortive drug sumatriptan, a 5-hydroxytryptamine 1B/1D agonist, inhibits CGRP-induced immediate vasodilation and headache.
We performed a double-blind, randomized, placebo-controlled, crossover study in 18 healthy volunteers. We recorded circumference changes of the middle meningeal artery (MMA) and middle cerebral artery (MCA) using magnetic resonance angiography before and after infusion (20 minutes) of 1.5 μg/min human αCGRP or placebo (isotonic saline) as well as after a 6-mg sumatriptan subcutaneous injection.
Compared with placebo, CGRP caused significant dilation of MMA (p = 0.006) and no dilation of MCA (p = 0.69). Sumatriptan caused a marked contraction of MMA (15%-25.2%) and marginal contraction of MCA (3.9% to 5.3%). Explorative analysis revealed that sumatriptan had a more selective action on MMA compared with MCA on the CGRP day (p < 0.0001) and on the placebo day (p = 0.007).
These data suggest that exogenous CGRP dilates extracranial vessels and not intracranial, and that sumatriptan exerts part of its antinociceptive action by constricting MMA and not MCA.
This study provides Class I evidence that IV GCRP causes dilation of the MMA but not the MCA in healthy volunteers, and that sumatriptan reverses the dilation of the MMA caused by CGRP.
降钙素基因相关肽（CGRP）在神经血管性头痛的病理生理学中起着至关重要的作用。CGRP 输注会引起头痛和颅血管扩张。然而，目前尚不清楚 CGRP 诱导的血管扩张在多大程度上导致了立即出现的头痛，以及偏头痛特异性的即刻缓解药物舒马曲坦（一种 5-羟色胺 1B/1D 激动剂）是否会抑制 CGRP 诱导的即刻血管扩张和头痛。
我们在 18 名健康志愿者中进行了一项双盲、随机、安慰剂对照、交叉研究。我们使用磁共振血管造影术在输注（20 分钟）1.5μg/min 人α CGRP 或安慰剂（等渗盐水）前后以及皮下注射 6mg 舒马曲坦后记录脑膜中动脉（MMA）和大脑中动脉（MCA）的周长变化。
与安慰剂相比，CGRP 引起 MMA 显著扩张（p = 0.006），而 MCA 无扩张（p = 0.69）。舒马曲坦引起 MMA 明显收缩（15%-25.2%）和 MCA 轻微收缩（3.9%-5.3%）。探索性分析显示，与 CGRP 日相比（p<0.0001）和安慰剂日相比（p=0.007），舒马曲坦对 MMA 的作用更具选择性，而对 MCA 的作用则不具选择性。
这些数据表明，外源性 CGRP 扩张颅外血管而不扩张颅内血管，舒马曲坦通过收缩 MMA 而不是 MCA 发挥其部分镇痛作用。
这项研究提供了 I 级证据，表明 IV GCRP 引起健康志愿者 MMA 扩张而不是 MCA 扩张，舒马曲坦逆转 CGRP 引起的 MMA 扩张。
