Among the diseases and disorders we have covered so far, many of them have been the result of aging, exposure to environmental factors, and/or inherited genetically. The effects of these diseases have also continuously progressed as aging continues. This week in Neurochemistry we tried to tackle the complex nature of migraines. Being fortunate enough not to have ever had a migraine, it made it hard to understand what people experience when a migraine is occurring. A few students in the class talked about their experiences with migraines and how they are so debilitating and the most painful thing that they have ever experienced. So we dug deep this week to try and understand what exactly is going on with migraines.
In the United States, about 1 in 4 households have someone who experiences migraines and over 10% of the population, including children, suffer from migraines. Women also experience migraines three times as often as men and migraines seem to have a genetic component. Research has shown, that a child has a 40% chance of suffering from migraines if one parent also suffers from them, and that chance goes up to 90% if both parents suffer from migraines. Migraines are most common to peak during what are called the “productive years” between the ages of 25 and 55. Because of the normal age ranges that many experience migraines, it is thought that stress may also be a factor leading to the development of migraines. During these years, many are finishing school, getting jobs or retiring, starting a family, and also in the older generation having secondary families. It is a hectic and stressful time for many.
So what exactly is happening during a migraine, and what causes some to experience them and others not to? It is not exactly known what causes migraines, but some research has shown that vasodilation could be a root cause of them. One believed cause of increased vasodilation, is in relation to the Calcitonin Gene-Related Peptide (CGRP). It is believed that alternative splicing of the calcitonin gene, which is produced in the periphery and central nervous system neurons, and result in increased vasodilation, leading to a migraine. Other pro-inflammatory agents are believed to be associated with migraine development as well, such as serotonin, bradykinin, histamine, and prostaglandin. These different chemicals are believed to irritate the pain receptors, nociceptors, in the area of the trigeminal nerve. The trigeminal nerve is the fifth cranial nerve that provides sensation for the face, and motor functions for mastication. The trigeminal nerve has three branches the ophthalmic, maxillary, and mandibular nerve branches. The ophthalmic branch of the trigeminal nerve is believed to be the main nerve affected in migraines, as it is located in the temporal region of the cranium where migraine pain is many times associated.
There are three main types of treatments that are used for migraines triptans, gepants, and glutamate antagonists. Triptans are of a family of tryptamine-based molecules that are used to treat only a single migraine episode. They work by acting as an agonists for 5-HT receptor, which are serotonin receptors, which are located on the blood vessels in the brain. When these receptors are activated they cause constriction of the blood vessels as well as inhibition of pro-inflammatory neuropeptide release, and triptans work to increase these 5-HT receptor activation. Some research has shown that triptans may actually work to inhibit the release of GCRP as well. Gepants are CGRP antagonist molecules, and are being developed in the hopes to help prevent migraines. These drugs have no vasoconstricitive properties, which prevent them from causing some of the vascular side affects seen with the use of triptans. The last are glutamate antagonists that work by inhibiting receptors that bind glutamate. By binding to these receptors it helps to limit the activity of glutamate and decreases the intracellular calcium levels, slowing the depolarization of the cell down, which helps to decrease the pain receptors signaling. Besides these drug treatments, Botox has also been used for treatment of migraines. Botox uses the botulin toxin in small concentrations to stop the communication of neurons. In Botox treatments, a small solution of botulin toxin is used in a localized area to help prevent nociceptors from communicating the signal of pain to the brain, relieving the pain that is experienced during a migraine. However, many of these treatments do not relieve the debilitating effects of migraines permanently.
When looking at the number of people who suffer from migraines, one thing is for sure; more research should be done to look at improving current treatments and looking for possible cures. Migraines prevent many from doing daily activities and many times inhibit any form of activity. Some people may deal with these monthly, or even as extreme as weekly, which can really decrease the quality of life in these individuals. To better improve the quality of life in these individuals, there needs to be a push for drug companies to expand their resources and help to develop drugs that prevent these mind splitting headaches.
References:
- http://www.migraineresearchfoundation.org/fact-sheet.html
