MIGRAINE PATHOLOGY & CAUSES: 

• Disease characterised by one sided headache (pain). There is a connection between vasodilators/vasoconstrictors and migraine. Drugs that cause vasodilation aren’t necessarily the culprits which precipitate migraines, especially if we take into consideration that anti-inflammatory drugs which have no direct vasoactive action, are also effective. Migraines aren’t simply caused by vasodilation within the brain as other drugs that do not have any direct vasoconstriction effects are still able to help with migraines. The pathophysiology of migraines are still poorly understood. The main culprits that have been identified to cause migraines involve trigeminal nerve distribution to intracranial arteries. The nerves release CGRP that are extremely powerful vasodilators. This most likely increases the intracranial pressure to such an extent that the “swelling” in the brain leads to pain, nausea, vomiting, visual scotomas. Medications that may help with migraine are in a large variety. Triptans, ergot alkaloids, NSAID’s, Beta blockers, Calcium channel blockers, tricyclic antidepressants, SSRI’s and several antiseizure agents all have a diminishing effect on migraines. Some of these drugs can only be used to prevent a migraine attack, or as a prophylactic, whilst others can be used during an attack.
• There are 2 hypotheses so far as to how these medications lessen the effects of migraines. The first one is that medications that fall under the classification as ergot alkaloids, triptans and antidepressants might activate the very specific serotonin receptor (5-HT1D/1B). This receptor can be found on the presynaptic trigeminal nerve ending. By agonizing the receptor – you inhibit the release of vasodilating peptides that would’ve led to increased intracranial pressure. Anti-seizure agents may suppress the excessive firing of these nerves. The second hypothesis argue that the direct vasoconstrictive effects of direct serotonin (5-HT) receptors may prevent vasodilation and stretching of pain endings. – some drugs work by both hypotheses. The second hypothesis has more to do with directly antagonizing the vasodilatory effects.
• So far sumatriptan is the first-line medication for migraines, but is contra indicated in coronary artery diseases. The mechanism of action is mainly debated as vasoconstrictor effects. Anti-inflammatory analgesics such as aspirin could also help. Beta blockers and some calcium channel blockers are good prophylactic medications to use for migraines by preventing vasodilation. Some anticonvulsants help as well. Verapamil also has modest efficacy as a prophylactic agent.