title: Comparison of the vasodilator responses of isolated human and rat middle meningeal arteries to migraine related compounds.
abstract: BACKGROUND
  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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Gustaf
authors.initials: G
authors.lastname: Grände
authors.forename: Sieneke
authors.initials: S
authors.lastname: Labruijere
authors.forename: Kristian Agmund
authors.initials: KA
authors.lastname: Haanes
authors.forename: Antoinette
authors.initials: A
authors.lastname: MaassenVanDenBrink
authors.affiliation: Department of Medicine, Institute of Clinical Science, Lund University, 221 84 Lund, Sweden. Lars.Edvinsson@med.lu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000502:physiology*; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013045:Species Specificity; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D018170:Sumatriptan / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D014665:Vasodilator Agents; D018170:Sumatriptan; D000068677:Sildenafil Citrate
references.citation: Lancet. 2008 Dec 20;372(9656):2115-23
references.pmid: 19036425
references.citation: Brain. 2003 Jan;126(Pt 1):241-7
references.pmid: 12477710
references.citation: Eur J Pharmacol. 2012 Jan 15;674(2-3):345-51
references.pmid: 22094063
references.citation: Cephalalgia. 2010 Oct;30(10):1179-86
references.pmid: 20855363
references.citation: J Magn Reson Imaging. 2006 Oct;24(4):918-21
references.pmid: 16958062
references.citation: Headache. 2010 May;50(5):909-16
references.pmid: 20546325
references.citation: Cephalalgia. 2012 Jan;32(2):140-9
references.pmid: 22174350
references.citation: Drugs. 1994 Apr;47(4):622-51
references.pmid: 7516861
references.citation: Headache. 2004 Oct;44(9):865-72
references.pmid: 15447695
references.citation: Lancet. 2010 Aug 21;376(9741):645-55
references.pmid: 20416945
references.citation: Lancet Neurol. 2013 May;12(5):454-61
references.pmid: 23578775
references.citation: Cephalalgia. 1997 May;17(3):166-74
references.pmid: 9170339
references.citation: Headache. 2012 Oct;52(9):1411-27
references.pmid: 22788114
references.citation: J Mol Neurosci. 2012 Nov;48(3):574-83
references.pmid: 22766684
references.citation: Neuropeptides. 2013 Apr;47(2):85-92
references.pmid: 23375386
references.citation: Cephalalgia. 2009 Aug;29(8):837-47
references.pmid: 19220306
references.citation: Neurology. 2010 Oct 26;75(17):1520-6
references.pmid: 20975053
references.citation: Brain. 2009 Jan;132(Pt 1):16-25
references.pmid: 19052139
references.citation: Cephalalgia. 2010 Mar;30(3):337-45
references.pmid: 19614687
references.citation: Cephalalgia. 1997 Jun;17(4):525-31
references.pmid: 9209774
references.citation: Cephalalgia. 2013 Feb;33(3):152-9
references.pmid: 23197351
references.citation: Cephalalgia. 2010 Feb;30(2):179-90
references.pmid: 19614689
references.citation: Pain. 2007 Jul;130(1-2):166-76
references.pmid: 17459586
references.citation: Eur J Clin Pharmacol. 1995;47(6):543-8
references.pmid: 7768259
references.citation: Eur J Pharmacol. 2007 Jul 12;567(1-2):117-24
references.pmid: 17477918
references.citation: Biochem Pharmacol. 2007 Aug 15;74(4):647-58
references.pmid: 17603024
references.citation: Brain Res. 2002 Nov 22;956(1):96-102
references.pmid: 12426051
references.citation: Eur J Pharmacol. 2011 Nov 16;670(1):186-94
references.pmid: 21914446
references.citation: Headache. 2009 Nov-Dec;49(10):1541-3
references.pmid: 19656222
references.citation: Clin Pharmacokinet. 1994 Nov;27(5):337-44
references.pmid: 7851052
references.citation: Ann Neurol. 2011 Apr;69(4):635-45
references.pmid: 21416486
references.citation: J Vestib Res. 2011;21(6):305-14
references.pmid: 22348935
references.citation: Neuroreport. 1993 Aug;4(8):1027-30
references.pmid: 8241457
references.citation: Cephalalgia. 1981 Dec;1(4):175-9
references.pmid: 6181893
references.citation: Ann Neurol. 2005 Nov;58(5):698-705
references.pmid: 16240341
references.citation: Circ Res. 1977 Jul;41(1):19-26
references.pmid: 862138
references.citation: Cephalalgia. 2003 Nov;23(9):877-86
references.pmid: 14616929
references.citation: Lancet Neurol. 2009 Jul;8(7):679-90
references.pmid: 19539239
references.citation: Cephalalgia. 2012 Aug;32(11):822-33
references.pmid: 22718556
references.citation: Cephalalgia. 2011 Apr;31(6):737-47
references.pmid: 21335366
references.citation: Eur J Pharmacol. 2004 Jun 16;493(1-3):133-7
references.pmid: 15189774
references.citation: Cephalalgia. 2011 Jan;31(2):181-9
references.pmid: 20974589
references.citation: Cephalalgia. 2008 Mar;28(3):226-36
references.pmid: 18254893
references.citation: Cephalalgia. 2008 Dec;28(12):1245-58
references.pmid: 18727638
references.citation: Br J Pharmacol. 2004 Nov;143(6):697-704
references.pmid: 15504760