Pathophysiology of Migraine.

OBJECTIVE This article provides an overview of the current understanding of migraine pathophysiology through insights gained from the extended symptom spectrum of migraine, neuroanatomy, migraine neurochemistry, and therapeutics. LATEST DEVELOPMENTS Recent advances in human migraine research, including human experimental migraine models and functional neuroimaging, have provided novel insights into migraine attack initiation, neurochemistry, neuroanatomy, and therapeutic substrates. It has become clear that migraine is a neural disorder, in which a wide range of brain areas and neurochemical systems are implicated, producing a heterogeneous clinical phenotype. Many of these neural pathways are monoaminergic and peptidergic, such as those involving calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide. We are currently witnessing an exciting era in which specific drugs targeting these pathways have shown promise in treating migraine, including some studies suggesting efficacy before headache has even started. ESSENTIAL POINTS Migraine is a brain disorder involving both headache and altered sensory, limbic, and homeostatic processing. A complex interplay between neurotransmitter systems, physiologic systems, and pain processing likely occurs. Targeting various therapeutic substrates within these networks provides an exciting avenue for future migraine therapeutics.