The Journal of Headache and Pain

"European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"

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Open Access

The serotonergic system in migraine

  • Massimo Leone1,
  • Andrea Rigamonti1,
  • Domenico D’Amico1,
  • Licia Grazzi1,
  • Susanna Usai1 and
  • Gennaro Bussone1
The Journal of Headache and PainOfficial Journal of the Italian Society for the Study of Headaches and the Italian Society of Pain Clinicians2:8


Serotonin (5–HT) and serotonin receptors play an important role in migraine pathophysiology. Changes in platelet 5–HT content are not casually related, but they may reflect similar changes at a neuronal level. Seven different classes of serotoninergic receptors are known, nevertheless only 5–HT2B–2C and 5HT1B–1D are related to migraine syndrome. Pharmacological evidences suggest that migraine is due to an hypersensitivity of 5–HT2B–2C receptors. m–Chlorophenylpiperazine (mCPP), a 5–HT2B–2C agonist, may induce migraine attacks. Moreover different pharmacological preventive therapies (pizotifen, cyproheptadine and methysergide) are antagonist of the same receptor class. On the other side the activation of 5–HT1B–1D receptors (triptans and ergotamines) induce a vasocostriction, a block of neurogenic inflammation and pain transmission.

SerotoninMigraineTriptans m–ChlorophenylpiperazinePathogenesis