Reported by Sascha Alles, Research Associate in the Snutch lab, Michael Smith Laboratories
Dr Stuart Cain, a Research Associate in Terry Snutch’s research lab is the lead author on a recent publication in Proceedings of the National Academy of Sciences of the United States of America (PNAS): In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures. Full article here.
The study in mice suggests a potential treatment for some forms of migraine with aura. The phenomenon that underlies migraine aura is called spreading depression or SD. This is a wave of neuronal activation followed by inactivity that travels through brain tissue.
Preliminary studies suggest that the pain drug pregabalin might help treat migraine with aura, but the drug’s efficacy remains unestablished. The main purpose of the study by Cain et al. was to provide further evidence for pregabalin as a potential therapy for migraine. “The study illustrates the power of integrating validated animal models of human disease with state of the art electrophysiological and imaging technologies in order to test hypotheses aimed at new therapeutic treatments” says senior author Prof Terry Snutch.
Much of our current understanding of migraine comes from mouse models of familial hemiplegic migraine (FHM-1). FHM-1 is a congenital form of the disease that causes hemiplegia (paralysis of half the side of the body) and in severe cases seizures, brain swelling and mild-head-trauma-induced coma.
Using advanced live neuroimaging (diffusion-weighted-MRI), Cain. examined pregabalin’s effects on mouse models of mild and severe forms of FHM-1 caused by distinct mutations in a subunit of a voltage-gated calcium channel. In the study, the author’s observed a unique pattern of SD spread in migraine mice involving the striatum and hippocampus. Pregabalin, which binds an auxiliary subunit of the voltage-gated calcium channel, increased the threshold of SD initiation in healthy, wild-type but not FHM1 mutant mice. Conversely, the drug slowed SD spread in migraine but not wild-type mice. According to the authors, pregabalin might represent a potential treatment for some forms of congenital and non-congenital migraine.
Lead author of the study Dr Stuart Cain says: “This research provides strong support for the need to undertake further clinical studies for the use of pregabalin in treating migraine. Further, this study has described a method of advanced neuroimaging that could be developed clinically to evaluate the brain swelling that occurs during migraine.”