Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Cephalalgia. 2011 Apr;31(5):537-42. doi: 10.1177/0333102410388433. Epub 2010 Nov 8.
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.
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.
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.
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.
皮质扩散性抑制是偏头痛先兆的电生理学基础，可能引发头痛。最近，五项偏头痛预防药物的慢性治疗显示可抑制皮质扩散性抑制，提示扩散性抑制可能成为偏头痛预防的共同治疗靶点。
为了评估扩散性抑制易感性作为临床前药物筛选工具的阴性预测值，我们测试了奥卡西平，一种在偏头痛预防中无效的抗癫痫药物。丙戊酸钠作为阳性对照。使用局部氯化钾或电刺激在大鼠中测量皮质扩散性抑制易感性。
奥卡西平无论是单次给药还是连续 5 周给药都没有抑制扩散性抑制。如前所述，丙戊酸钠在慢性给药后抑制了扩散性抑制易感性，而单次给药则无效。
这些数据为扩散性抑制作为偏头痛预防的相关靶点提供了进一步支持，并证明了所采用的扩散性抑制模型的预测效用。
