Comparison of the vasodilator responses of isolated human and rat middle meningeal arteries to migraine related compounds

The Journal of Headache and Pain

Research Article

Kristian Agmund Haanes¹  Sieneke Labruijere²  Antoinette MaassenVanDenBrink²  Gustaf Grände³  Lars Edvinsson⁴ 

[1] Department of Clinical Experimental Research, Copenhagen University Hospital, Glostrup, Denmark;Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands;Department of Medicine, Institute of Clinical Science, Lund University, 221 84, Lund, Sweden;Department of Medicine, Institute of Clinical Science, Lund University, 221 84, Lund, Sweden;Department of Clinical Experimental Research, Copenhagen University Hospital, Glostrup, Denmark;

关键词: Vasodilation;    Middle meningeal artery;    Migraine;    CGRP;   

DOI  :  10.1186/1129-2377-15-22

 received in 2014-03-14, accepted in 2014-04-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMigraine attacks occur spontaneously in those who suffer from the condition, but migraine-like attacks can also be induced artificially by a number of substances. Previously published evidence makes the meninges a likely source of migraine related pain. This article investigates the effect of several vasodilators on meningeal arteries in order to find a connection between the effect of a substance on a meningeal vessel and its ability to artificially induce migraine.MethodsA myograph setup was used to test the vasodilator properties of the substances acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil, prostaglandin E2 (PGE2), pituitary adenylate cyclase activating peptide-38 (PACAP-38), calcitonin gene-related peptide (CGRP) and NaCl buffer on meningeal arteries from human and rat. An unpaired t-test was used to statistically compare the mean Emax(%) at the highest concentration of each substance to the Emax(%) of NaCl buffer.ResultsIn the human experiments, all substances except PACAP-38 had an Emax (%) higher than the NaCl buffer, but the difference was only significant for SNP and CGRP. For the human samples, clinically tested antimigraine compounds (sumatriptan, telcagepant) were applied to the isolated arteries, and both induced a significant decrease of the effect of exogenously administrated CGRP. In experiments on rat middle meningeal arteries, pre-contracted with PGF2α, similar tendencies were seen. When the pre-contraction was switched to K+ in a separate series of experiments, CGRP and sildenafil significantly relaxed the arteries.ConclusionsStill no definite answer can be given as to why pain is experienced during an attack of migraine. No clear correlation was found between the efficacy of a substance as a meningeal artery vasodilator in human and the ability to artificially induce migraine or the mechanism of action. Vasodilatation could be an essential trigger, but only in conjunction with other unknown factors. The vasculature of the meninges likely contributes to the propagation of the migrainal cascade of symptoms, but more research is needed before any conclusions can be drawn about the nature of this contribution.

【 授权许可】

Unknown   
© Grände et al.; licensee Springer. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.