The online version of this article (doi:10.1186/1129-2377-15-22) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
Conceived and designed the experiments: GG, SL, KAH, AMvdB, LE. Performed the experiments: GG, SL, KAH. Analyzed the data: GG, SL, KAH, AMvdB. Contributed reagents/materials/analysis tools: AMvdB, LE. Wrote the paper: GG, SL, KAH, AMvdB, LE. All authors read and approved the final manuscript.
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 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.
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.
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.
Ray BS, Wolff HG: Experimental studies on headache-pain-sensitive structures of the head and their significance in headache. Arch Surg-Chicago 1940, 41(4):813–856. 10.1001/archsurg.1940.01210040002001 CrossRef
Wienecke T, Olesen J, Ashina M: Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs. Cephalalgia 2010, 30(2):179–190. PubMed
Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M: PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 2009, 132(Pt 1):16–25. PubMed
Schytz HW, Wienecke T, Olesen J, Ashina M: Carbachol induces headache, but not migraine-like attacks, in patients with migraine without aura. Cephalalgia 2010, 30(3):337–345. PubMed
Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, Leibensperger H, Froman S, Assaid C, Lines C, Koppen H, Winner PK: Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet 2008, 372(9656):2115–2123. 10.1016/S0140-6736(08)61626-8 CrossRefPubMed
Teixeira CE, Jin L, Priviero FB, Ying Z, Webb RC: Comparative pharmacological analysis of Rho-kinase inhibitors and identification of molecular components of Ca2+ sensitization in the rat lower urinary tract. Biochem Pharmacol 2007, 74(4):647–658. 10.1016/j.bcp.2007.06.004 PubMedCentralCrossRefPubMed
Chan KY, Baun M, de Vries R, van den Bogaerdt AJ, Dirven CM, Danser AH, Jansen-Olesen I, Olesen J, Villalon CM, MaassenVanDenBrink A, Gupta S: Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery. Cephalalgia 2011, 31(2):181–189. 10.1177/0333102410375624 CrossRefPubMed
Amin FM, Asghar MS, Hougaard A, Hansen AE, Larsen VA, de Koning PJ, Larsson HB, Olesen J, Ashina M: Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol 2013, 12(5):454–461. 10.1016/S1474-4422(13)70067-X CrossRefPubMed
- Comparison of the vasodilator responses of isolated human and rat middle meningeal arteries to migraine related compounds
Kristian Agmund Haanes
- Springer Milan
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