The role of the brainstem in migraine: Potential brainstem effects of CGRP and CGRP receptor activation in animal models.

The brainstem forms a functional unit with several hypothalamic nuclei that are capable of modulating diverse functions including migraine-relevant trigeminal pain processing, appetite and arousal regulatory networks. As such, the brainstem has emerged as a key regulator of migraine and is appropriately considered as a potential therapeutic target. While currently available CGRP targeted therapies have limited blood brain barrier penetrability, the expression of CGRP and its receptors in several key brainstem nuclei and the demonstration of brainstem effects of CGRP modulation highlight the significant potential for the development of CNS penetrant molecules.