Suppression of cortical spreading depression in migraine prophylaxis

Ayata C., Jin H., Kudo C., DALKARA T., Moskowitz M. A.

Annals of Neurology, vol.59, no.4, pp.652-661, 2006 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 59 Issue: 4
  • Publication Date: 2006
  • Doi Number: 10.1002/ana.20778
  • Journal Name: Annals of Neurology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.652-661
  • Hacettepe University Affiliated: Yes


Objective: Topiramate, valproate, propranolol, amitriptyline, and methysergide have been widely prescribed for migraine prophylaxis, but their mechanism or site of action is uncertain. Cortical spreading depression (CSD) has been implicated in migraine and as a headache trigger and can be evoked in experimental animals by electrical or chemical stimulation. We hypothesized that migraine prophylactic agents suppress CSD as a common mechanism of action. Methods: Rats were treated either acutely or chronically over weeks and months, with one of the above migraine prophylactic drugs, vehicle, or D-propranolol, a clinically ineffective drug. The impact of treatment was determined on the frequency of evoked CSDs after topical potassium application or on the incremental cathodal stimulation threshold to evoke CSD. Results: Chronic daily administration of migraine prophylactic drugs dose-dependently suppressed CSD frequency by 40 to 80% and increased the cathodal stimulation threshold, whereas acute treatment was ineffective. Longer treatment durations produced stronger CSD suppression. Chronic D-propranolol treatment did not differ from saline control. Interpretation: Our data suggest that CSD provides a common therapeutic target for widely prescribed migraine prophylactic drugs. Assessing CSD threshold may prove useful for developing new prophylactic drugs and improving upon existing ones. © 2006 American Neurological Association.