Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache

Migraine is a debilitating disorder that afflicts over 1 billion people worldwide, involving attacks that result in a throbbing and pulsating headache. Migraine is thought to be a neurovascular event associated with vasoconstriction, vasodilation, and neuronal activation. Understanding signaling in migraine pathology is central to the development of therapeutics for migraine prophylaxis and for mitigation of migraine in the prodrome phase before pain sets in. The fact that both vasoactivity and neural sensitization are involved in migraine indicates that agonists which promote these phenomena may very well be involved in migraine pathology. One such group of agonists is the purines, in particular, adenosine phosphates and their metabolites. This manuscript explores what is known about the relationship between these metabolites and migraine pathology and explores the potential for such relationships through their known signaling pathways. Reported receptor involvement in vasoaction and nociception.