Ayata C
Stroke and Neurovascular Regulation Laboratory, Department of Radiology, and Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cephalalgia. 2009 Oct;29(10):1095-114. doi: 10.1111/j.1468-2982.2009.01982.x.
Despite the relatively well-characterized headache mechanisms in migraine, upstream events triggering individual attacks are poorly understood. This lack of mechanistic insight has hampered a rational approach to prophylactic drug discovery. Unlike targeted abortive and analgesic interventions, mainstream migraine prophylaxis has been largely based on serendipitous observations (e.g. propranolol) and presumed class effects (e.g. anticonvulsants). Recent studies suggest that spreading depression is the final common pathophysiological target for several established or investigational migraine prophylactic drugs. Building on these observations, spreading depression can now be explored for its predictive utility as a preclinical drug screening paradigm in migraine prophylaxis.
尽管偏头痛的头痛机制已得到较好的描述，但引发个体发作的上游事件却知之甚少。这种对机制的缺乏了解阻碍了预防性药物发现的合理方法。与有针对性的终止发作和镇痛干预不同，主流的偏头痛预防主要基于偶然观察（如普萘洛尔）和假定的类别效应（如抗惊厥药）。最近的研究表明，扩散性抑制是几种已确立或正在研究的偏头痛预防性药物的最终共同病理生理靶点。基于这些观察结果，现在可以探索扩散性抑制作为偏头痛预防临床前药物筛选范例的预测效用。
