Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of headache and pain, 2018-05, Vol.19 (1), p.1-10, Article 41

Ort / Verlag

Milan: Springer Milan

Erscheinungsjahr

2018

Link zum Volltext

Quelle

SpringerNature Journals

Beschreibungen/Notizen

• 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 A 2A receptor antagonists with varying selectivity over A 1 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 A 2A 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 A 1 receptor. Conclusions These results suggest that vascular adenosine A 2A (and, to a certain extent, also A 1 ) 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 A 2A receptor antagonism may offer a novel approach to antimigraine therapy which remains to be investigated in clinical trials.