Cain, SM;
Bohnet, B;
LeDue, J;
Yung, AC;
Garcia, E;
Tyson, JR;
Alles, SRA;
... Snutch, TP; + view all
(2017)
In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures.
PNAS - Proceedings of the National Academy of Sciences of the United States of America
, 114
(9)
pp. 2401-2406.
10.1073/pnas.1614447114.
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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.
| Type: | Article |
|---|---|
| Title: | In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.1614447114 |
| Publisher version: | http://doi.org/10.1073/pnas.1614447114 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, familial hemiplegic migraine type 1, migraine, diffusion-weighted MRI, voltage-gated calcium channel, gabapentinoids, FAMILIAL HEMIPLEGIC MIGRAINE, ENHANCED EXCITATORY TRANSMISSION, RAT NEOCORTICAL SLICES, CALCIUM-CHANNEL, HIPPOCAMPAL-NEURONS, MOUSE MODEL, GABAPENTIN, CA(V)2.1, RELEASE, MICE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10042804 |
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