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Suppression of cortical spreading depression in migraine prophylaxis.
Ann Neurol 2006; 59(4):652-61AN

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.

Authors+Show Affiliations

Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16450381

Citation

Ayata, Cenk, et al. "Suppression of Cortical Spreading Depression in Migraine Prophylaxis." Annals of Neurology, vol. 59, no. 4, 2006, pp. 652-61.
Ayata C, Jin H, Kudo C, et al. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59(4):652-61.
Ayata, C., Jin, H., Kudo, C., Dalkara, T., & Moskowitz, M. A. (2006). Suppression of cortical spreading depression in migraine prophylaxis. Annals of Neurology, 59(4), pp. 652-61.
Ayata C, et al. Suppression of Cortical Spreading Depression in Migraine Prophylaxis. Ann Neurol. 2006;59(4):652-61. PubMed PMID: 16450381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of cortical spreading depression in migraine prophylaxis. AU - Ayata,Cenk, AU - Jin,Hongwei, AU - Kudo,Chiho, AU - Dalkara,Turgay, AU - Moskowitz,Michael A, PY - 2006/2/2/pubmed PY - 2006/6/3/medline PY - 2006/2/2/entrez SP - 652 EP - 61 JF - Annals of neurology JO - Ann. Neurol. VL - 59 IS - 4 N2 - 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. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/16450381/Suppression_of_cortical_spreading_depression_in_migraine_prophylaxis_ L2 - https://doi.org/10.1002/ana.20778 DB - PRIME DP - Unbound Medicine ER -