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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 TPdoi
10.1073/pnas.1614447114subject
Has Abstractpub_date
2017-02-28 00:00:00pages
2401-2406issue
9eissn
0027-8424issn
1091-6490pii
1614447114journal_volume
114pub_type
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