Document Detail


Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers.
MedLine Citation:
PMID:  20975053     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 μg/min human αCGRP 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.
Authors:
M S Asghar; A E Hansen; T Kapijimpanga; R J van der Geest; P van der Koning; H B W Larsson; J Olesen; M Ashina
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurology     Volume:  75     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-26     Completed Date:  2010-11-12     Revised Date:  2011-08-25    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1520-6     Citation Subset:  AIM; IM    
Affiliation:
Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Adult
Area Under Curve
Blood Pressure / drug effects
Calcitonin Gene-Related Peptide / adverse effects,  pharmacology*
Confidence Intervals
Double-Blind Method
Drug Interactions
Female
Headache / chemically induced
Humans
Magnetic Resonance Angiography / methods
Magnetic Resonance Imaging / methods
Male
Meningeal Arteries / drug effects*,  physiology
Middle Cerebral Artery / drug effects,  physiology
Sumatriptan / pharmacology*
Vasoconstrictor Agents / pharmacology*
Vasodilation / drug effects*
Vasodilator Agents / pharmacology*
Young Adult
Chemical
Reg. No./Substance:
0/Vasoconstrictor Agents; 0/Vasodilator Agents; 103628-46-2/Sumatriptan; 83652-28-2/Calcitonin Gene-Related Peptide
Comments/Corrections
Comment In:
Neurology. 2010 Oct 26;75(17):1494-5   [PMID:  20975050 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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