Rescue Therapy for Acute Migraine, Part 1

Triptans, Dihydroergotamine, and Magnesium

Nancy E. Kelley, MD, PhD; Deborah E. Tepper, MD

Disclosures

Headache. 2012;52(1):114-128. 

In This Article

Pathophysiology of Migraine and Potential Targets for Treatment

Whatever the anatomical site of migraine biogenesis, "migraine process" clearly involves meningeal mechanisms that activate nociceptive afferents that carry signals back to the brainstem.[18] Migraine with aura is thought to involve cortical spreading depression which progresses anteriorly from the visual cortex at a rate of 3–4 mm/minute and produces a consequent reduction in regional cerebral blood flow (oligemia).[19]

The perception of head pain involves transduction and transmission of pain signals from pain receptors and the interpretation of these pain signals by centrally located structures. Pain signals may arise from receptors located in the dura mater, the meningeal vessels, the intracranial segments of CN V, CN IX, and CN X, and the intracranial segments of the basilar, vertebral, and carotid arteries; all can transmit pain signals to the trigeminal nucleus caudalis (TNC) in the medulla and to the dorsal horn of the upper cervical spine.[18] The activity of second order neurons in those two areas can be modified by inputs from the nucleus raphe magnus (serotonergic), periaqueductal gray area, locus ceruleus (noradrenergic), and rostral trigeminal nuclei, and by descending inhibitory transmissions from the cerebral cortex. These correspondingly modified signals are then relayed to the contralateral dorsomedial and ventroposteromedial nuclei of the thalamus, a common destination for pain transmissions, and then on to the insular cortex, the anterior cingulate cortex, and the somatosensory cortex.

Treatments for acute migraine, therefore, potentially may target the pain circuitry peripherally, centrally, or both. During the natural course of a migraine attack, both initial peripheral sensitization and, in most cases, subsequent central pain sensitization occurs.

During peripheral sensitization, primary afferent neurons may become irritable and increase their spontaneous firing because of neurogenic inflammation and dilation of meningeal blood vessels. With the onset of migraine, there is increased release of substance P, inflammatory cytokines, and the vasodilator calcitonin gene-related peptide (CGRP), a potential vasodilator. There is also increased mast cell degranulation and release of histamine, sensitizing the individual to small changes in intracranial pressure, and causing the characteristic throbbing quality of migraine pain.[20]

Central sensitization is often marked by the development of cutaneous allodynia (the perception of pain in response to a normally non-painful stimulus), and this may involve the scalp, face, and even the arms. Cutaneous allodynia occurs in 79% of migraineurs.[21] During central sensitization, the excitatory thresholds of second order neurons in the TNC and the dorsal horn of the cervical spine is reduced.[22]

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