Animal models of migraine headache and aura

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.