In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures.
Proc Natl Acad Sci U S A
; 114(9): 2401-2406, 2017 02 28.
Article
em En
| MEDLINE
| ID: mdl-28223480
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.
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Base de dados:
MEDLINE
Assunto principal:
Depressão Alastrante da Atividade Elétrica Cortical
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Bloqueadores dos Canais de Cálcio
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Ataxia Cerebelar
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Enxaqueca com Aura
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Canais de Cálcio Tipo N
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Pregabalina
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Analgésicos
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Transtornos de Enxaqueca
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article