Migraine preventive drugs differentially affect cortical spreading depression in rat

Volodymyr Borysovych Bogdanov, Sylvie Multon, Virginie Chauvel, Olena Viktorivna Bogdanova, Dimiter Prodanov, Mykola Yukhymovych Makarchuk, Jean Schoenen
Neurobiology of Disease. 2011-02-01; 41(2): 430-435
DOI: 10.1016/j.nbd.2010.10.014

PubMed
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Cortical spreading depression (CSD) is the most likely cause of the migraine
aura. Drugs with distinct pharmacological properties are effective in the
preventive treatment of migraine. To test the hypothesis that their common
denominator might be suppression of CSD we studied in rats the effect of three
drugs used in migraine prevention: lamotrigine which is selectively effective on
the aura but not on the headache, valproate and riboflavin which have a
non-selective effect. Rats received for 4 weeks daily intraperitoneal injections
of one of the three drugs. For valproate and riboflavin we used saline as
control, for lamotrigine its vehicle dimethyl sulfoxide. After treatment,
cortical spreading depressions were elicited for 2h by occipital KCl application.
We measured CSD frequency, its propagation between a posterior
(parieto-occipital) and an anterior (frontal) electrode, and number of
Fos-immunoreactive nuclei in frontal cortex. Lamotrigine suppressed CSDs by 37%
and 60% at posterior and anterior electrodes. Valproate had no effect on
posterior CSDs, but reduced anterior ones by 32% and slowed propagation velocity.
Riboflavin had no significant effect at neither recording site. Frontal Fos
expression was decreased after lamotrigine and valproate, but not after
riboflavin. Serum levels of administered drugs were within the range of those
usually effective in patients. Our study shows that preventive anti-migraine
drugs have differential effects on CSD. Lamotrigine has a marked suppressive
effect which correlates with its rather selective action on the migraine aura.
Valproate and riboflavin have no effect on the triggering of CSD, although they
are effective in migraine without aura. Taken together, these results are
compatible with a causal role of CSD in migraine with aura, but not in migraine
without aura.

 

Auteurs Bordeaux Neurocampus