The pathogenesis of migraine is obscure. A hyperexcitable brain state has been postulated. Cortical spreading depression (CSD) is the most suggestive argument for the brain hyperexcitability. It has been showed that valproate, topiramate, amitriptyline and propranolol inhibit CSD in rats, which suggests that most preventative treatments of migraine act by normalising neuronal firing and increasing a genetically lowered and environmentally modified threshold for neuronal discharge. It has also been suggested that some antimigraine prophylactic drugs (i.e., amitriptyline, candesartan and magnesium) may act by restoring central nociceptive dysmodulation.