In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures.

Abstract:

:Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2.1 (P/Q-type) calcium channel subunit, pregabalin slowed the speed of SD propagation in vivo. Acute systemic administration of pregabalin in vivo also selectively prevented the migration of SD into subcortical striatal and hippocampal regions in the R192Q strain that exhibits a milder phenotype and gain of CaV2.1 channel function. At the cellular level, pregabalin inhibited glutamatergic synaptic transmission differentially in WT, R192Q, and S218L mice. The study describes a DW-MRI analysis method for tracking the progression of SD and provides support and a mechanism of action for pregabalin as a possible effective therapy in the treatment of migraine.

authors

Cain SM,Bohnet B,LeDue J,Yung AC,Garcia E,Tyson JR,Alles SR,Han H,van den Maagdenberg AM,Kozlowski P,MacVicar BA,Snutch TP

doi

10.1073/pnas.1614447114

subject

Has Abstract

pub_date

2017-02-28 00:00:00

pages

2401-2406

issue

9

eissn

0027-8424

issn

1091-6490

pii

1614447114

journal_volume

114

pub_type

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