MIGRAINE

1. MIGRAINE Anna Madueke Physiology 3

2. What is a migraine? • Condition marked by recurring moderate to severe headaches • Unilateral throbbing pain • Worsens with movement • Known to cause nausea, sensitivity to light/sound, vomiting

3. Causes • Genetics • Environmental factors (sounds, light, smell, movement, food) • Stress • Lack of sleep

4. Genetics and Migraines • Demonstrated in twin studies; monozygotic (identical) twins were more likely to both experience migraines than dizygotic (fraternal) twins • Molecular genetic era began with research which showed that mutations on the α1A subunit on chromosome 19 were responsible for familial hemiplegic migraine in some families • Research suggests that variations within the dopamine D2 receptor genes might have some effect on susceptibility to migraines

5. Environment and Migraines • Weather change • Light • Sounds • Odors • Altitude change • Physical factors (neck pain, toothaches)

6. Migraine Phases • Prodrome: irritability, food cravings, nausea, difficulty sleeping (few hours - days) • Aura: visual disturbances, numbness or tingling in body, temporary loss of sight (5-6 minutes) • Migraine Attack: throbbing pain, nausea, vomiting, anxiety, insomnia (4-72 hours) • Postdrome: inability to concentrate, fatigue, depressed mood, euphoric mood, lack of comprehension

7. Vascular Theory of Migraine • Theory behind development of Triptans medication which was thought to stop migraine pain by vasoconstricting blood vessels • The most recent studies show that calcitonin gene-related peptide (CGRP) treatments such as olcegepant and telcagepant were effective in relieving migraines without vasoconstriction

8. Theory of Cortical Spreading Depression • Slowly propagating wave of neuronal and glial depolarization followed by prolonged inhibition of cortical activity • Starts in cortex, moves into thalamus, into brain stem, travels to sensory cortex (pain caused here) • Trigeminal nerve branches near thalamus, trigeminal nerve activated • Pain is usually felt on one side of head due to direct stimulation of trigeminal nerve from thalamus • Thalamus becomes inflamed, trigeminal nerve becomes inflamed

9. Anatomy of a Migraine • Cerebral vessels, pial vessels, venous sinuses, and dura mater are surrounded by unmyelinated fibers that arise from the ophthalmic division of the trigeminal ganglion, as well as from the upper cervical roots • Trigeminal fibers that innervate cerebral vessels arise from neurons (in trigeminal ganglion) that contain Substance P and Calcitonin gene-related peptide

10. Neuropeptides Substance P (SP): neuropeptide that acts as neurotransmitter in transmission of signals from pain receptors Calcitonin Gene-related Peptide (CGRP): produces dilatation of dural vessels and increase in blood flow

11. Activation of Trigeminovascular Pathway • ⅓ of all migraines are preceded by somatosensory, or motor or visual symptoms known as aura • Visual aura: most frequent, perception of light flashes moving across visual field (associated with Cortical Spreading Depression [CSD]) • At the molecular and cellular level, CSD is shown to be involved in the release of ATP, glutamate, Potassium, hydrogen ions, cortical gene-related peptide, and nitric oxide • Molecules diffuse towards surface of cortex where they activate nociceptors, triggering inflammation and vasodilation

12. Migraine Pathophysiology Continued • Without triptans, pain impulses are carried to trigeminal nucleus caudalis (in brainstem) • Pain signals are relayed to higher order neurons in the thalamus, resulting in referred pain (head, neck, face)

13. Triptans • Tryptamine-based drug that relieves migraine pains by interfering with vasodilation progression • Triptans bind to 5HT1B receptors on meningeal blood vessels, decreases vasodilation • Also binds to same receptors on trigeminal nerve endings around blood vessels which block the release of neuropeptides, which reduces vasodilation and inflammation • Ex: Imitrex, zoloft