University of Central Florida Undergraduate Research Journal - Analysis of the Pathomechanism and Treatment of Migraines Related to the Role of the Neuropeptide CGRP
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Current Treatment of Migraine

Prophylactic treatments are used to treat acute migraine attack, and are currently used as strategies to treat migraine headaches. Treatment methods include such first-line drugs as triptans and NSAIDS; in addition, anti-epileptic drugs, antidepressants, beta-blockers, and natural supplements are used to treat migraines (Table 1)4. Acupuncture, as well as other non-drug treatments, is used as well.

Medications

Drugs are utilized in the asymptomatic phase between acute attacks where no symptoms are observable while in the prophylaxis of a migraine2. These drugs include Timolol and Propranolol, which are both beta–blockers. Propranolol has been foundto act by inhibiting cortical spreading depression in the aura phase of migraines, and a possible method of action to achieve this inhibition effect has been through the blockage of glutamate release41. For patients with depression or sleep issues, Amitriptyline, a tricyclic antidepressant, is used40. Drugs such as Divalproex, an anticonvulsant, and Verapamil, a calcium channel blocker, are aso used2.

Acute attack treatment is divided into prodromal phase and headache phase. The prodromal phase is described by aura and neurological symptoms that are experienced prior to the actual headache26. Treatment applied during the prodromal phase is conducted by the Triptan family, which includes drugs such as Zolmitriptan, Naratriptan, Rizatriptan, Eletriptan, Almotriptan, and Sumitriptan, all of which have been shown to quickly decrease migraine headaches in patients2. Sumatriptan is the most widely used antimigraine drug, and is the most effective antimigraine prophylactic drug. This drug brings elevated CGRP back to normal levels and also relieves the headache in studies that have been conducted43. Triptan oral administration inhibits gastrointestinal mobility and thus may not completely relieve pain, and as such various other methods of administration such as nasal spray or subcutaneous injection may provide more effective treatment44.

Triptans have been found to be more effective when administered during the headache phase rather than during the aura phase45. In fact, the general oral treatment of migraine attacks (as recommended by the European Federation of Neurological Sciences) should take place earlier during the headache phase to prevent incorrect absorption that may take place during the migraine46. But if a non-oral administration of triptans is being given, the most effective period to administer the drugs has been found to be just prior to the symptoms of the migraine becoming severe48. A side effect of triptan drugs, however, is that they constrict coronary arteries, leading to chest tightness and pain, which can in turn create significant side effects in patients suffering from coronary diseases49.

Another drug given during the prodromal phase is the vasoconstrictor Dihydroergotamine, a derivative of ergotamine. This drug should not be used while pregnant or by patients that have coronary artery disease because nausea is a side effect. These triptan drugs have been shown to be effective in most cases50.

The headache phase is associated with cerebral vasodilation as well as symptoms that include nausea or vomiting, and analgesics such as non-steroid antiinflammatory drugs (NSAIDs) are used for treatment26. These symptoms are not specific and act on many different receptors and molecules such as cyclooxygenase and other inflammation-related receptors. Naproxen, meclogenamate, and aspirin are common NSAIDs used for antimigraine treatment50. If the pain is severe, opioids, mepreidine, or codeine sulphate can be used to decrease pain. Opiates specifically decrease the calcium influx (pre–synaptic) and increase the potassium efflux (post–synaptic), which then decreases the duration of the action potential by decreasing the positive charge inside the postsynaptic terminal. Anti–emetic drugs are used to treat nausea, examples of which are domperidone and metoclopramide51. Mediction overuse is lower in patients that are using triptan rather than analgesics, and opioids have been shown to have a lower efficiency at treating migraines overall52.

Epilepsy and migraines have similar clinical features, and as such antiepileptic drugs can also be used for antimigraine treatment due to their prevention of the stimulation of the brainstem4. Topiramate, gabapentin, and valproate are involved with gamma-aminobutyric acid by increasing the inhibition of GABA. Gabapentin and valproate alter GABA metabolism, leading to its eventual inhibition53. Topiramate also inhibits the action of GABA, but does so by acting on the receptors. In various double–blind trials, the actions of these drugs have been shown to be more positive than a placebo54. Topiramate has also been shown to prevent the exocytosis of CGRP and thus prevent vasodilation as well by directly acting on trigeminal sensory nerves55.

For a severe migraine attack, the first drugs of choice are Sumatriptan administered subcutaneously and acetylsalicylic acid administered intravenously. Steroids can help treat a status migrainosus. Betablockers, topiramate, valproic acid, and flunarizine are the first choice to treat the prophylaxis of migraines. Second choice drugs are bisoprolol, naproxen, petasites, and amitriptyline51.

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