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The Journal of Headache and Pain
Published in: The Journal of Headache and Pain 1/2018

Open Access 01-12-2018 | Research article

Characterization of the trigeminovascular actions of several adenosine A2A receptor antagonists in an in vivo rat model of migraine

Authors: Kristian A. Haanes, Alejandro Labastida-Ramírez, Kayi Y. Chan, René de Vries, Brian Shook, Paul Jackson, Jimmy Zhang, Christopher M. Flores, Alexander H. J. Danser, Carlos M. Villalón, Antoinette MaassenVanDenBrink

Published in: The Journal of Headache and Pain | Issue 1/2018

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Abstract

Background

Migraine is considered a neurovascular disorder, but its pathophysiological mechanisms are not yet fully understood. Adenosine has been shown to increase in plasma during migraine attacks and to induce vasodilation in several blood vessels; however, it remains unknown whether adenosine can interact with the trigeminovascular system. Moreover, caffeine, a non-selective adenosine receptor antagonist, is included in many over the counter anti-headache/migraine treatments.

Methods

This study used the rat closed cranial window method to investigate in vivo the effects of the adenosine A2A receptor antagonists with varying selectivity over A1 receptors; JNJ-39928122, JNJ-40529749, JNJ-41942914, JNJ-40064440 or JNJ-41501798 (0.3–10 mg/kg) on the vasodilation of the middle meningeal artery produced by either CGS21680 (an adenosine A2A receptor agonist) or endogenous CGRP (released by periarterial electrical stimulation).

Results

Regarding the dural meningeal vasodilation produced neurogenically or pharmacologically, all JNJ antagonists: (i) did not affect neurogenic vasodilation but (ii) blocked the vasodilation produced by CGS21680, with a blocking potency directly related to their additional affinity for the adenosine A1 receptor.

Conclusions

These results suggest that vascular adenosine A2A (and, to a certain extent, also A1) receptors mediate the CGS21680-induced meningeal vasodilation. These receptors do not appear to modulate prejunctionally the sensory release of CGRP. Prevention of meningeal arterial dilation might be predictive for anti-migraine drugs, and since none of these JNJ antagonists modified per se blood pressure, selective A2A receptor antagonism may offer a novel approach to antimigraine therapy which remains to be investigated in clinical trials.
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Metadata
Title
Characterization of the trigeminovascular actions of several adenosine A2A receptor antagonists in an in vivo rat model of migraine
Authors
Kristian A. Haanes
Alejandro Labastida-Ramírez
Kayi Y. Chan
René de Vries
Brian Shook
Paul Jackson
Jimmy Zhang
Christopher M. Flores
Alexander H. J. Danser
Carlos M. Villalón
Antoinette MaassenVanDenBrink
Publication date
01-12-2018
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2018
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-018-0867-x

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