PATHOPHYSIOLOGY OF MIGRAINE HEADACHES
A migraine headache is a neurovascular disorder often initiated by a trigger and characterized by a headache, which is preceded by a visual aura 20% of the time. The headache may be accompanied by a variety of multiple organ system symptoms, such as allodynia, nausea, vomiting, and urinary frequency. There are various types of migraine, the diagnostic criteria for which are established by the International Headache Society.4 The types of migraine are divided into two groups: migraine without aura (“common migraine”) and migraine with aura (“classic migraine”). Further subdivisions include migraine with typical aura with or without headache, familial hemiplegic migraine, sporadic hemiplegic migraine, basilar type migraine, and retinal migraine.4
The initiation of migraines is not fully understood, but likely involves genetic abnormalities in central nervous system (CNS) ion channels that predispose patients to specific triggers. Patients with familial hemiplegic migraine, an autosomal dominant disorder, have missense mutations in the α1 subunit of brain specific P/Q voltage-gated calcium channels resulting in altered function of these channels. During migraines, the upper brainstem has increased blood flow and is implicated as a “migraine generator.” After activation, a wave of cortical depression spreads across the cortex from a caudal to rostral fashion followed by a spreading wave of oligemia, which can produce the auras that occur in 20% of migraineurs.26,36,86 Current theories suggest that this spreading wave also occurs in patients who do not experience visual auras but spares the visual cortex.
Cephalalgia begins during vasoconstriction prior to vasodilation. Antidromic activation of the afferent neurons of the ophthalmic division of the trigeminal nerve and branches of the C1 and C2 nerves (first order neurons) located on dural arteries at the base of the brain releases inflammatory neuropeptides such as calcitonin gene-related polypeptide (CRGP), vasoactive intestinal peptide (VIP), and neurokinase A. Vasoactive neuropeptides, including serotonin, nitric oxide, substance P, neurokinin A, and calcitonin gene-related peptide (CGRP), are released during this process, which exacerbates the vasodilation and irritates the meninges at the base of the brain, causing further pain. CGRP from trigeminal A-δ-fibers produces dural vasodilation, while substance P and neurokinin A from trigeminal C-fibers increase dural vessel permeability.24,26 Pain impulses are relayed orthodromically to the trigeminal nucleus caudalis (second order neurons) in the lower medulla and upper cervical spinal cord, then to the thalamus (third order neurons) via the quintothalamic tract, and finally to higher cortical areas (fourth order neurons probably located in the limbi cortex).26,34 The trigeminocervical complex also produces retrograde parasympathetic impulses from the sphenopalatine ganglion and the superior salivatory nucleus in the pons through the pterygopalatine, otic, and carotid ganglia to the cerebral vessels.34
Treatment of migraines encompasses a wide variety of xenobiotics that can be broadly classified as prophylactic or abortive therapies (Table 54–1). Current abortive therapies include analgesics (nonsteroidal antiinflammatory drugs, acetaminophen ...