Abstract The pathogenesis of migraine pain has not yet been adequately explained and remains the subject of vigorous debate. Early studies by Harold Wolff and his associates on the extracranial terminal branches of the external carotid artery provided compelling evidence of their involvement in the evolution of migraine pain. They postulated that migraine pain emanates from dilated extracranial arteries. Since 1958, however, when Milner proposed that the visual aura of migraine may be caused by the "spreading depression" of Leão, migraine research has focused almost exclusively on the central neurovascular changes, to the exclusion of Wolff's postulates. Current theories implicate changes in the trigeminovascular system, which is defined as comprising the trigeminal subnucleus caudalis, the trigeminal nerve, and the intracranial arteries, particularly the middle meningeal artery. Although the middle meningeal artery is intracranial, it is one of the terminal branches of the external carotid artery. In this chapter experimental, clinical, and pharmacological evidence linking the extracranial terminal branches of the external carotid artery to migraine pain is presented
