Migraine

Pathology

Migraine involves the release of the peptide neurotransmitter, calcitonin gene-related peptide (CGRP), from nerves distributed in cerebral arteries.  This neurotransmitter causes vasodilation and extravasation of blood plasma and plasma proteins into the perivascular space (perivascular oedema).  This causes a mechanical stretching which in turn lead to the activation of pain nerve endings in the dura.

Current treatments

Triptans (e.g. Sumatriptan) are first-line therapy for migraines. They are partial agonists at serotonin 1B/1D receptors and increase intracranial vasoconstriction that prevents the above-mentioned vasodilation that causes pain due to the stretching of sensory nerve endings. These agents may also reduce the release of CGRP and as a result also reduces perivascular oedema in the intracranial circulation.

Ergot alkaloids (e.g. Ergotamine and Ergonovine) have mixed partial agonist effects at serotonin 2 receptors and alpha adrenoceptors. They cause marked smooth muscle contraction but blocks alpha-agonist vasoconstriction. These agents therefore also prevent the above-mentioned vasodilation that leads to pain.