Pathophysiology
Clinical meaning
Migraine is a complex neurovascular disorder driven by activation of the trigeminovascular system. The current pathophysiological model involves cortical spreading depression (CSD), a wave of neuronal and glial depolarization that slowly propagates across the cerebral cortex at 3-5 mm per minute, followed by sustained neuronal suppression. CSD is the physiological substrate of migraine aura, producing the characteristic expanding scintillating scotoma and sensory march. CSD activates trigeminal afferents in the meninges, triggering the release of calcitonin gene-related peptide (CGRP), substance P, and neurokinin A from perivascular nerve terminals. CGRP produces potent meningeal vasodilation and promotes neurogenic inflammation with plasma protein extravasation and mast cell degranulation. Nociceptive signals travel via the trigeminal ganglion to the trigeminocervical complex in the brainstem, then ascend to the thalamus and somatosensory cortex, producing the perception of headache pain. Central sensitization develops when sustained peripheral nociceptive input lowers the activation threshold of second-order and third-order trigeminal neurons, manifesting clinically as cutaneous allodynia (scalp tenderness, pain from wearing glasses or earrings). The ICHD-3 diagnostic criteria operationalize these mechanisms: migraine without aura requires at least 5 attacks lasting 4-72...