Migraine pathology

Migraine involves the trigeminal nerve distribution to intracranial (and possibly extracranial) arteries, which release peptide neurotransmitters especially CGRP (Calcitonin Gene-Related Peptide) which is a strong vasodilator. Substance P and neurokinin A may also be involved. Extravasation of plasma and plasma proteins into the perivascular space is a common feature of animal migraine models and is found in biopsy specimens from migraine patients. The mechanical stretching caused by this perivascular edema may be the immediate cause of activation of pain nerve endings in the dura.

The onset of headache is sometimes associated with a marked increase in the amplitude of temporal artery pulsations, and relief of pain by administration of effective therapy is sometimes accompanied by diminution of these pulsations.

Current Treatment for migraines and how it works

The triptans (Sumatriptan, Rizatriptan), the Ergot Alkaloids (Ergotamine, Dihydroergotamine), and the Antidepressants (Amitriptyline, Nortriptyline) may activate 5-HT_1D/1B receptors on presynaptic trigeminal nerve endings to inhibit the release of vasodilating peptides, and antiseizure agents may suppress excessive firing of these nerve endings. The vasoconstrictor actions of direct 5-HT agonists (the triptans and ergot) may prevent vasodilation and stretching of the pain endings. It is possible that both mechanisms contribute in the case of some drugs.