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Review
. 2015 Jul:94:64-71.
doi: 10.1016/j.neuropharm.2014.12.015. Epub 2015 Jan 9.

ASICs as therapeutic targets for migraine

Greg Dussor  1
Affiliations
Review

ASICs as therapeutic targets for migraine

Greg Dussor. Neuropharmacology. 2015 Jul.

Abstract

Migraine is the most common neurological disorder and one of the most common chronic pain conditions. Despite its prevalence, the pathophysiology leading to migraine is poorly understood and the identification of new therapeutic targets has been slow. Several processes are currently thought to contribute to migraine including altered activity in the hypothalamus, cortical-spreading depression (CSD), and afferent sensory input from the cranial meninges. Decreased extracellular pH and subsequent activation of acid-sensing ion channels (ASICs) may contribute to each of these processes and may thus play a role in migraine pathophysiology. Although few studies have directly examined a role of ASICs in migraine, studies directly examining a connection have generated promising results including efficacy of ASIC blockers in both preclinical migraine models and in human migraine patients. The purpose of this review is to discuss the pathophysiology thought to contribute to migraine and findings that implicate decreased pH and/or ASICs in these events, as well as propose issues to be resolved in future studies of ASICs and migraine. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.

Keywords: ASIC; Cortical spreading depression; Dura; Headache; Meninges; Migraine.

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Conflict of interest statement

The author declares no conflict of interest in relation to this work.

Figures

Figure 1
Figure 1. Mechanisms and ASIC subtypes that may play a role in the various phases of migraine
Hypothalamic activity is thought to drive both premonitory symptoms and to modulate incoming afferent activity from the meninges. Multiple ASIC subtypes and ASIC activity are present throughout the hypothalamus. A role for ASIC1 has been demonstrated in CSD, a process that may underlie aura, but can also lead to inflammatory events and afferent activity in the meninges. Whether CSD can propagate into the hypothalamus and contribute to migraine is not clear. ASIC3 can contribute to activation of meningeal afferents resulting in headache. ASIC1 participates in pain signaling from peripheral tissues but has not yet been linked to meningeal afferent activity.
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