Animal migraine models for drug development: status and future perspectives.

Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related responses are likely to be behavioral, allowing multiple experiments in each individual animal. Distinction is made between acute and prophylactic models and how to validate each of them. Modern insight into neurobiological mechanisms of migraine is so good that it is only a question of resources and efforts that determine when valid models with ability to predict efficacy in migraine will be available.