Migraine pathophysiology 1st principles

The fundamental principles underlying the pathophysiology of migraine involve complex neurovascular and neurochemical mechanisms.

Migraine is primarily a neurovascular disorder characterized by episodic attacks of moderate to severe headache, often accompanied by symptoms such as photophobia, phonophobia, nausea, and vomiting. These attacks can last between 4 to 72 hours and are typically unilateral with pulsating quality NICE CKS.

The pathophysiological process involves activation of the trigeminovascular system, which includes trigeminal sensory nerves innervating intracranial blood vessels and the meninges. Upon activation, these nerves release neuropeptides such as calcitonin gene-related peptide (CGRP), which plays a critical role by causing vasodilation of intracranial and extracranial blood vessels and modulating vascular nociception centrally NICE CKS Villalón & Olesen 2009.

CGRP release leads to dilation and plasma protein extravasation in meningeal vessels, resulting in inflammation and sensitization of trigeminal nociceptors. This neurogenic inflammation is thought to contribute to the pulsatile headache characteristic of migraine NICE CKS Villalón & Olesen 2009.

Additionally, migraine aura symptoms, when present, are believed to result from cortical spreading depression — a wave of neuronal and glial depolarization that spreads across the cerebral cortex, leading to transient focal neurological symptoms such as visual disturbances or sensory changes NICE CKS Blumenfeld et al. 2023.

The neurovascular hypothesis is further supported by the efficacy of pharmacological agents such as triptans, which are selective agonists of 5-HT1B/1D receptors. These receptors mediate vasoconstriction of dilated intracranial vessels and inhibit further release of neuropeptides like CGRP, thereby aborting migraine attacks SmPC Naramig Martelletti et al. 2008.

Overall, migraine is a complex disorder involving dysregulation of vascular tone, neuropeptide release, and central nervous system processing of pain, with CGRP playing a key role in the development of headache and associated symptoms NICE CKS Villalón & Olesen 2009 Blumenfeld et al. 2023.