Journal
JOURNAL OF HEADACHE AND PAIN
Volume 19, Issue -, Pages -Publisher
SPRINGER-VERLAG ITALIA SRL
DOI: 10.1186/s10194-018-0867-x
Keywords
Adenosine receptor; CGS21680; Dural vasodilation; Rat; vasodepressor response
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Funding
- Janssen Research Development
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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 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 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 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.
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