BACKGROUND: Cortical spreading depression is the electrophysiological substrate of migraine aura, and may trigger headache. Recently, chronic treatment with five migraine prophylactic drugs was shown to suppress cortical spreading depression, implicating spreading depression as a common therapeutic target in migraine prophylaxis. MATERIALS AND METHODS: In order to assess the negative predictive value of spreading depression susceptibility as a preclinical drug screening tool, we tested oxcarbazepine, an anti-epileptic ineffective in migraine prophylaxis. Valproate served as the positive control. Cortical spreading depression susceptibility was measured in rats using topical KCl or electrical stimulation. RESULTS: Oxcarbazepine did not suppress spreading depression either after a single dose or after daily treatment for 5 weeks. As previously shown, valproate suppressed spreading depression susceptibility after chronic dosing, while a single dose was ineffective. CONCLUSIONS: These data provide further support for spreading depression as a relevant target in migraine prophylaxis, and demonstrate the predictive utility of employed spreading depression models.
BACKGROUND: Cortical spreading depression is the electrophysiological substrate of migraine aura, and may trigger headache. Recently, chronic treatment with five migraine prophylactic drugs was shown to suppress cortical spreading depression, implicating spreading depression as a common therapeutic target in migraine prophylaxis. MATERIALS AND METHODS: In order to assess the negative predictive value of spreading depression susceptibility as a preclinical drug screening tool, we tested oxcarbazepine, an anti-epileptic ineffective in migraine prophylaxis. Valproate served as the positive control. Cortical spreading depression susceptibility was measured in rats using topical KCl or electrical stimulation. RESULTS:Oxcarbazepine did not suppress spreading depression either after a single dose or after daily treatment for 5 weeks. As previously shown, valproate suppressed spreading depression susceptibility after chronic dosing, while a single dose was ineffective. CONCLUSIONS: These data provide further support for spreading depression as a relevant target in migraine prophylaxis, and demonstrate the predictive utility of employed spreading depression models.
Authors: Alessandro Tozzi; Antonio de Iure; Massimiliano Di Filippo; Cinzia Costa; Stefano Caproni; Antonio Pisani; Paola Bonsi; Barbara Picconi; Letizia M Cupini; Serena Materazzi; Pierangelo Geppetti; Paola Sarchielli; Paolo Calabresi Journal: Proc Natl Acad Sci U S A Date: 2012-10-29 Impact factor: 11.205