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- Title
Suppression of cortical spreading depression in migraine prophylaxis.
- Authors
Ayata C; Jin H; Kudo C; Dalkara T; Moskowitz MA
- Abstract
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.
- Publication
Annals of Neurology, 2006, Vol 59, Issue 4, p652
- ISSN
0364-5134
- Publication type
Journal Article