An update on the blood vessel in migraine

Abstract

Purpose of review: The cranial blood vessel is considered an integral player in the pathophysiology of migraine, but its perceived role has been subject to much discussion and controversy over the years. We will discuss the evolution in our scientific understanding of cranial blood vessels (primarily arteries) in migraine.

Recent findings: Recent developments have clarified the role of cranial blood vessels in the trigemino-vascular system and in cortical spreading depression. An underlying theme is the intimate relation between vascular activity and neural function, and we will emphasize the various roles of the blood vessel that go beyond delivering blood. We conclude that migraine cannot be understood, either from a research or clinical point of view, without an understanding of the vascular derangements that accompany it.

Summary: Migraine is accompanied by significant derangements in vascular function that may represent important targets for investigation and treatment.

Figure 1

The varied regulation of the cerebral artery Schematic shows a cortical surface artery, with its penetrator branches and arterioles in the cortex itself. The surface vessel is heavily innervated by sensory fibers from the trigeminal ganglion (TG), parasympathetic fibers from the sphenopalatine and otic ganglia (SPG/OG), and sympathetic fibers from the superior cervical ganglion (SCG). Peripheral innervation trails off as arteries enter the cortex, and regulation switches primarily to more local mechanisms. Inset: the ‘neurovascular unit’ consists of astrocytes which contact local neurons as well as arterioles (via their end-feet). Neurovascular coupling is mediated by the astrocyte, which transduces signals from neural activity (glutamate, K⁺) either directly or indirectly onto the vessel, causing dilation and increased blood flow. Interneurons have been shown to contact vessels directly, though the significance of these contacts is debated. Finally, ascending projections from brainstem nuclei can modulate cortical arterial diameter (note that they can also do this through effects on the trigeminal, parasympathetic, and sympathetic nerves that contact surface vessels). The differential regulation of cerebral vessels is highly relevant to migraine: cortical surface vessels are likely conduits for migraine-associated pain; and parenchymal microvessels are in close apposition to the neurons involved in cortical migraine phenomena. 5HT, serotonin; ACh, acetylcholine; CGRP, calcitonin gene-related peptide; GABA, g-amino butyric acid; glu, glutamate; NA, norepinephrine; NKA, neurokinin A; NOS, nitric oxide synthase; NPY, neuropeptide Y; PACAP, pituitary adenylate cyclase activating peptide; PNS, peripheral nervous system; SOM, somatostatin; SP, substance P; VIP, vasoactive intestinal peptide. Reproduced with permission from [2].