Pharmacological targeting of spreading depression in migraine

Abstract

Migraine, particularly with aura, is a genetically heterogeneous disorder of ion channels, pumps or transporters associated with increased cortical excitability. Spreading depression, as one reflection of hyperexcitability, is the electrophysiological event underlying aura symptoms and a trigger for headache. Endogenous (e.g., genes and hormones) and exogenous factors (e.g., drugs) modulating migraine susceptibility have also been shown to modulate spreading depression susceptibility concordantly, suggesting that spreading depression can be a relevant therapeutic target in migraine. In support of this, several migraine prophylactic drugs used in clinical practice have been shown to suppress spreading depression susceptibility as a probable mechanism of action, despite belonging to widely different pharmacological classes. Hence, susceptibility to spreading depression can be a useful preclinical model with good positive and negative predictive value for drug screening.

Keywords::

• animal models
• hormones
• ion channels
• migraine
• prophylaxis
• spreading depression

Financial & competing interests disclosure

This work was in part supported by the NIH (NS061505), Harvard Catalyst – The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centers) and American Heart Association (SDG 2610275). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.