Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/108972

In Collections

This item can be found in the following collections:

Asghar, M.S.; Hansen, A.E.; Kapijimpanga, T.; Geest, R.J. van der; Koning, P. van der; Larsson, H.B.W.; ... ; Ashina, M. (2010)

Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers

Article / Letter to editor
Background: 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. Methods: 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 mu g/min human alpha CGRP or placebo (isotonic saline) as well as after a 6-mg sumatriptan subcutaneous injection. Results: Compared with placebo, CGRP caused significant dilation of MMA (p = 0.006) and no dilation of MCA (p = 0.69). Sumatriptan caused...Show moreBackground: 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. Methods: 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 mu g/min human alpha CGRP or placebo (isotonic saline) as well as after a 6-mg sumatriptan subcutaneous injection. Results: 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). Conclusion: 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. Classification of evidence: 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. Neurology (R) 2010;75:1520-1526Show less
gene-related peptide magnetic-resonance angiography healthy-volunteers migraine headache nitric-oxide in-vitro bibn4096bs humans rat vasodilatation
All authors
Asghar, M.S.; Hansen, A.E.; Kapijimpanga, T.; Geest, R.J. van der; Koning, P. van der; Larsson, H.B.W.; Olesen, J.; Ashina, M.
Date
2010-10-26
Journal
Neurology
Volume
75
Issue
17
Pages
1520 - 1526
DOI
doi:10.1212/WNL.0b013e3181f9626a