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Suppression of cortical spreading depression in migraine prophylaxis
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. Ann Neurol 2006
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Cited by
Pathophysiology of migraine: a disorder of sensory processing
Goadsby, P. J., Holland, P. R., Martins-Oliveira, M., Hoffmann, J., Schankin, C., & Akerman, S. (2017) · Physiological Reviews · doi:10.1152/physrev.00034.2015 · Cited by 1,998
Noseda, R., & Burstein, R. (2013) · Pain · doi:10.1016/j.pain.2013.07.021 · Cited by 871
Chronic migraine: risk factors, mechanisms and treatment
May, A., & Schulte, L. H. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.93 · Cited by 630
Cortical spreading depression causes and coincides with tissue hypoxia
Takano, T., Tian, G.-F., Peng, W., Lou, N., Lovatt, D., Hansen, A. J., Kasischke, K. A., & Nedergaard, M. (2007) · Nature Neuroscience · doi:10.1038/nn1902 · Cited by 472
Progress report on new antiepileptic drugs: A summary of the Eigth Eilat Conference (EILAT VIII)
Bialer, M., Johannessen, S. I., Kupferberg, H. J., Levy, R. H., Perucca, E., & Tomson, T. (2007) · Epilepsy Research · doi:10.1016/j.eplepsyres.2006.10.008 · Cited by 477
Metadata
- Authors
- Ayata, C., Jin, H., Kudo, C., Dalkara, T., & Moskowitz, M. A.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2006-01-31
- Volume
- 59
- Issue
- 4
- Pages
- 652-661
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2091509461
- Cited by
- 570
- References
- 0
- FWCI
- 22.61
- Type
- journal article
- Language
- en
- Open access
- closed
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- Ayata, C., Jin, H., Kudo, C., Dalkara, T., & Moskowitz, M. A. (2006). Suppression of cortical spreading depression in migraine prophylaxis. Annals of Neurology. https://doi.org/10.1002/ana.20778
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