What is the role of serotonin in the pathogenesis of migraine?

Updated: Aug 15, 2019
  • Author: William C Robertson, Jr, MD; Chief Editor: Amy Kao, MD  more...
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Serotonin (5-hydroxytryptamine, or 5-HT) also seems to play a role in the pathogenesis of migraine. Intermittent neuronal discharges from serotonergic neurons in the pons may cause an initial discharge in the ipsilateral occipital cortex. This discharge could then cause a wave of spreading excitation followed by depression of neuronal activity.

During a migraine attack, urine levels of the serotonin metabolite hydroxyindoleacetic acid increase significantly. Serotonin is released from platelets at the beginning of an attack. After onset and for the duration of the headache, intraplatelet serotonin levels decrease. Serotonin turnover is also reduced during a migraine attack. Between attacks, however, migraineurs have increased synthesis of serotonin.

In addition, several serotonin receptors appear to be important in the pathophysiology of migraine. The 3 most important receptors are 5-HT1, 5-HT2, and 5-HT3. The 5-HT1 receptors are inhibitory, and the 5-HT2 receptors are excitatory. All triptans are 5-HT1 agonists, while many prophylactic agents (eg, beta blockers) are 5-HT2 antagonists. An injection of serotonin during an attack decreases migraine symptoms but is associated with many unpleasant adverse effects.

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