A 27-year-old woman comes to the office due to severe, unilateral, throbbing headaches that occur several times a month. The headaches are associated with photophobia, nausea, and occasional vomiting. Over-the-counter analgesics do not provide significant symptom relief. Her mother has a history of similar headaches. Vital signs are within normal limits. Physical examination reveals no abnormalities. A medication is prescribed to treat her condition and the patient is instructed to take it immediately at the onset of a headache. This medication most likely decreases the severity and duration of this patient's headache through which of the following mechanisms?
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Migraines are recurrent, debilitating, unilateral headaches with a pulsating or throbbing quality lasting between 4-72 hours, often with photophobia, phonophobia, and nausea. They can be associated with an aura and are more common in younger women.
Although the pathogenesis of migraines is multifactorial and not fully understood, it is associated with cortical spreading depression (ie, self-propagating neurotransmission across the cortex). Subsequent stimulation of trigeminal afferents in the meninges causes the release of vasoactive neuropeptides, including substance P and calcitonin gene–related peptide (CGRP), leading to neurogenic inflammation, vasodilation, and plasma protein extravasation. These substances may also contribute to the increased sensitivity of nociceptive pathways to stimuli (ie, neuronal sensitization).
Triptans (eg, sumatriptan) are serotonin 5-hydroxytryptamine 1B/1D agonists that directly counter migraine headaches by binding to trigeminal serotonin receptors and inhibiting CGRP release from the trigeminal neurons. In addition, triptans bind serotonin receptors on the smooth muscle cells of blood vessels, resulting in intracranial vasoconstriction. Triptans are commonly prescribed as abortive therapy for acute migraines, particularly in patients who are not responsive to analgesics. Significant adverse effects include dizziness, chest tightness, and hypertension.
(Choice A) Antipsychotic medications (eg, haloperidol, risperidone) block the dopamine receptors in the mesolimbic tract and are used in schizophrenia or bipolar disorder. They are not indicated in the treatment of migraine.
(Choice B) Selective serotonin reuptake inhibitors (eg, sertraline, citalopram) block serotonin reuptake in cortico-amygdala pathways. These drugs are used to treat depression and anxiety, not to abort migraines.
(Choice C) Acetylcholinesterase inhibitors (eg, rivastigmine, galantamine) increase the availability of acetylcholine at cortical synapses and are indicated in the treatment of dementia (eg, Alzheimer disease).
(Choice D) Opioid medications (eg, morphine, oxycodone) stimulate mu receptors in the periaqueductal gray area, resulting in modulation of pain. Opioids are not indicated in the treatment of migraines because they increase the risk of chronic migraine, carry a risk of dependence, and are less effective than triptans.
Educational objective:
The pathogenesis of migraines is complex and multifactorial but includes neurogenic inflammation, vasodilation, and sensitization of trigeminal afferents in the meninges. Triptans are serotonin 5-hydroxytryptamine 1B/1D agonists that stimulate the trigeminovascular serotonin receptors, resulting in inhibition of vasoactive peptide release, intracranial vasoconstriction, and decreased pain. They are used as abortive therapy for acute migraine.