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

Abstract

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.

Dural administration of inflammatory soup or Complete Freund’s Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

“…Interestingly, the IS caused a strong contraction of the artery, whereas nothing occurred with the artery tone following the CFA administration. Vasodilatation has been suggested to be the initiator of migraine, but could also be a consequence or a side phenomenon [ 44 ] and it has previoulsy been shown that not all migraine attacks are associated with vasodilation [ 45 ]. An earlier study supporting the vascular hypothesis found that a short period of vasoconstriction triggers the release of vasodilator agents, such as CGRP, and could explain some of the findings presented here [ 42 ].…”

The role of the blood–brain barrier in the development and treatment of migraine and other pain disorders

“…Migraine presents two subtypes, migraine with aura and migraine without aura ( Silberstein et al, 2005 ). Although a large number of recent studies have tried to establish the migraine pathophysiology ( Bhaskar et al, 2013 ; Noseda and Burstein, 2013 ; Sarrouilhe et al, 2014 ; Thissen et al, 2014 ), the role of the neural and vascular mechanisms in this process has been largely discussed in the literature, ( Asghar et al, 2011 ; Grände et al, 2014 ). As a matter of fact, there is still a debate whether the source of the pain is in the nerves around the cranial arteries, CNS or both ( Goadsby et al, 2009 ; Olesen et al, 2009 ).…”

“…Collectively, those results suggest a key role of cranial blood vessels in the migraine pathophysiology. In fact, meningeal arteries lack BBB and represent much more permeable structures, compared with cortical vessels ( Edvinsson and Tfelt-Hansen, 2008 ; Grände et al, 2014 ). There have been considerable advances in the understanding of the sequence of events that lead to a migraine headache.…”

Ultrasonographic assessment of the maxillary artery and middle meningeal artery in the infratemporal fossa

“…On the other hand, there are no studies reporting visualizing the MMA or assessing its blood flow. Ultrasonographic visualization of the MXA and its MMA branch in ITF may allow their assessment in headache and migraine, intracranial hematomas, and extracranial‐intracranial by‐pass surgery, as well as to assess collateral flow development in carotid occlusive diseases and the vascularization of tumors and vascular malformations of the facial region …”

“…Ultrasonographic visualization of the MXA and its MMA branch in ITF may allow their assessment in headache and migraine, intracranial hematomas, and extracranial-intracranial by-pass surgery, as well as to assess collateral flow development in carotid occlusive diseases and the vascularization of tumors and vascular malformations of the facial region. 2,[6][7][8][9][10] The aim of this study was to develop and present a method to visualize the MMA and MXA in the ITF, correctly identify these two arteries based on their anatomy and blood-flow features, and describe their hemodynamic characteristics in a group of subjects without vascular disease. After the visualization of the arteries, we measured the depth of insonation (DI), and obtained the pulsed Doppler signal of the MXA and the MMA, on which we measured the angle corrected peak We anticipated that the Doppler spectrum characteristics of MXA and MMA would be intermediate between those of extra and intracranial arteries 12,13 (Figure 3).…”