• Clément Verkest, Emilie Piquet, Sylvie Diochot, Mélodie Dauvois, Michel Lanteri-Minet, Eric Lingueglia, and Anne Baron.
• Université Côte d'Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
• Br. J. Pharmacol. 2018 Nov 1; 175 (21): 4154-4166.

Background And PurposeAcid-sensing ion channels (ASICs) are neuronal proton sensors emerging as potential therapeutic targets in pain of the orofacial region. Amiloride, a non-specific ASIC blocker, has been shown to exert beneficial effects in animal models of migraine and in patients. We explored the involvement of the ASIC1-subtype in cutaneous allodynia, a hallmark of migraine affecting cephalic and extra-cephalic regions in about 70% of migrainers.Experimental ApproachWe investigated the effects of systemic injections of amiloride and mambalgin-1, a specific inhibitor of ASIC1a- and ASIC1b-containing channels, on cephalic and extra-cephalic mechanical sensitivity in a rodent model of acute and chronic migraine induced by i.p. injections of isosorbide dinitrate.Key ResultsI.v. injections of these inhibitors reversed cephalic and extra-cephalic acute cutaneous mechanical allodynia in rats, a single injection inducing a delay in the subsequent establishment of chronic allodynia. Both mambalgin-1 and amiloride also reversed established chronic allodynia. The anti-allodynic effects of mambalgin-1 were not altered in ASIC1a-knockout mice, showing the ASIC1a subtype is not involved in these effects which were comparable to those of the anti-migraine drug sumatriptan and of the preventive drug topiramate on acute and chronic allodynia respectively. A single daily injection of mambalgin-1 also had a significant preventive effect on allodynia chronification.Conclusions And ImplicationsThese pharmacological data support the involvement of peripheral ASIC1-containing channels in migraine cutaneous allodynia as well as in its chronification. They highlight the therapeutic potential of ASIC1 inhibitors as both an acute and prophylactic treatment for migraine.© 2018 The British Pharmacological Society.

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