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

Grände, Gustaf LU ; Labruijere, Sieneke; Haanes, Kristian Agmund; MaassenVanDenBrink, Antoinette and Edvinsson, Lars LU (2014) In Journal of Headache and Pain 15.
Abstract
Migraine 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. A myograph setup was used to test the vasodilator properties of the substances acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil, prostaglandin E-2 (PGE(2)), pituitary adenylate cyclase activating peptide-38 (PACAP-38), calcitonin gene-related peptide (CGRP) and NaCl... (More)
Migraine 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. A myograph setup was used to test the vasodilator properties of the substances acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil, prostaglandin E-2 (PGE(2)), 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 E-max(%) at the highest concentration of each substance to the E-max(%) of NaCl buffer. In the human experiments, all substances except PACAP-38 had an E-max (%) 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 PGF(2 alpha), 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. Still 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Vasodilation, Middle meningeal artery, Migraine, CGRP
in
Journal of Headache and Pain
volume
15
publisher
Springer
external identifiers
  • wos:000336226700001
  • scopus:84907736535
ISSN
1129-2369
DOI
10.1186/1129-2377-15-22
language
English
LU publication?
yes
id
5dc6eb3a-dde3-452d-8642-5ead2851dc06 (old id 4470121)
date added to LUP
2014-07-01 07:40:38
date last changed
2017-11-05 03:18:25
@article{5dc6eb3a-dde3-452d-8642-5ead2851dc06,
  abstract     = {Migraine 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. A myograph setup was used to test the vasodilator properties of the substances acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil, prostaglandin E-2 (PGE(2)), 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 E-max(%) at the highest concentration of each substance to the E-max(%) of NaCl buffer. In the human experiments, all substances except PACAP-38 had an E-max (%) 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 PGF(2 alpha), 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. Still 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.},
  articleno    = {22},
  author       = {Grände, Gustaf and Labruijere, Sieneke and Haanes, Kristian Agmund and MaassenVanDenBrink, Antoinette and Edvinsson, Lars},
  issn         = {1129-2369},
  keyword      = {Vasodilation,Middle meningeal artery,Migraine,CGRP},
  language     = {eng},
  publisher    = {Springer},
  series       = {Journal of Headache and Pain},
  title        = {Comparison of the vasodilator responses of isolated human and rat middle meningeal arteries to migraine related compounds},
  url          = {http://dx.doi.org/10.1186/1129-2377-15-22},
  volume       = {15},
  year         = {2014},
}