• Migraine
• Pathology

Migraine involves the trigeminal nerve distribution to instracranial, and possibly extracranial, arteries. These nerve release peptide neurotansmitters, especially calcitonin gene-related peptide, CGRP, an extremely powerful vasodilator. Substance P and neurokinin A may also be involved. 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. A migraine is also characterized by nausea, vomiting and visual scotomas or even hemianopsia and speech abnormalities.

• Current treatment and mechanism of action:

Triptans e.g. Sumatriptan: The first line drug therapy for acute severe migraines. These drugs are selective agonist for 5-HT 1D and 5-HT 1B receptors. They activate these receptors on the presynaptic trigeminal nerve ends to inhibit the release of the vasodilating peptides. Triptans should not be used in patients with coronary artery disease because they have the ability to cause coronary vasospasms.

Lasmiditan: Is a highly selective 5-HT 1F receptor agonist and is effective in treating migraines. The agent lacks vasoconstriction actions and is a much more cardiovascular save than the triptans. The drug reduces trigeminal nerve stimulation-induced plasma and plasma protein extravasation in dura vessels. Lasmiditan is used in acute migraines.

Ergot alkaloids e.g. Ergotamine and Ergonovine: The ergot derivates have mixed partial agonist effects at 5-HT2 and at alpha adrenoceptors. These drugs cause a marked smooth muscle contraction but they also block alpha agonist vasoconstriction. These agents therefore also prevent the above-mentioned vasodilation that leads to pain.

Anti-inflammatory analgesics e.g. aspirin/ibuprofen: These drugs are helpful in controlling the pain of the migraine, but not resolving the migraine itself.