Eikermann-Haerter Katharina, Moskowitz Michael A
Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Curr Opin Neurol. 2008 Jun;21(3):294-300. doi: 10.1097/WCO.0b013e3282fc25de.
Over the past 30 years, animal models of migraine have led to the identification of novel drug targets and drug treatments as well as helped to clarify a mechanism for abortive and prophylactic drugs. Animal models have also provided translational knowledge and a framework to think about the impact of hormones, genes, and environmental factors on migraine pathophysiology. Although most acknowledge that these animal models have significant shortcomings, promising new drugs are now being developed and brought to the clinic using these preclinical models. Hence, it is timely to provide a short overview examining the ways in which animal models inform us about underlying migraine mechanisms.
First generation migraine models mainly focused on events within pain-generating intracranial tissues, for example, the dura mater and large vessels, as well as their downstream consequences within brain. Upstream events such as cortical spreading depression have also been modeled recently and provide insight into mechanisms of migraine prophylaxis. Mouse mutants expressing human migraine mutations have been genetically engineered to provide an understanding of familial hemiplegic migraine and possibly, by extrapolation, may reflect on the pathophysiology of more common migraine subtypes.
Animal models of migraine reflect distinct facets of this clinically heterogeneous disorder and contribute to a better understanding of its pathophysiology and pharmacology.
在过去30年中,偏头痛动物模型已促使新型药物靶点和药物治疗方法得以确定,同时也有助于阐明终止发作药物和预防性药物的作用机制。动物模型还提供了转化知识以及一个思考激素、基因和环境因素对偏头痛病理生理学影响的框架。尽管大多数人都承认这些动物模型存在显著缺陷,但目前正在利用这些临床前模型开发有前景的新药并将其推向临床。因此,适时提供一个简短综述,探讨动物模型让我们了解偏头痛潜在机制的方式很有必要。
第一代偏头痛模型主要关注产生疼痛的颅内组织内的事件,例如硬脑膜和大血管,以及它们在脑内的下游后果。诸如皮层扩散性抑制等上游事件最近也已被建模,并为偏头痛预防机制提供了见解。已通过基因工程构建表达人类偏头痛突变的小鼠突变体,以了解家族性偏瘫性偏头痛,并且通过推断,可能有助于反映更常见偏头痛亚型的病理生理学。
偏头痛动物模型反映了这种临床异质性疾病的不同方面,有助于更好地理解其病理生理学和药理学。