So is this what causes the pain? Well, yes and no. We know that these areas of the brainstem—the raphé nucleus, and the locus cœruleus—are important in the maintenance of mood and the processing of pain. Other brainstem areas, the substantia nigra and the red nucleus, were previously thought to be more important for normal movement, and we have found recently that they have a role in headache pain as well.
But that's not the whole migraine pain story. We still haven't gotten to the inside of your head, really. Everything we have talked about so far has happened at the base of the brain or on its surface. And we haven't really covered that in detail yet.
Based on research, the best understanding we now have is that migraine arises from abnormally excitable neurons in the brain and trigeminal nerves. What causes the neurons to be abnormally excitable? Various things can do this, including low magnesium, abnormal calcium channels on the surface of the neuron, mitochondrial abnormalities, or other inherited brain chemical abnormalities.
The trigeminal nerves start in the brainstem in the trigeminal nucleus caudalis, and travel to your face, teeth, eyes, sinuses, and forehead. They also go to the blood vessels on the surface of the brain. So, now we have excitable neurons, and dilating blood vessels. These make up what we call the trigeminovascular system, or trigeminovascular theory of migraine.
Once the messages come from the activated cells in the trigeminal nucleus in the brainstem, and travel to the trigeminal nerves that go to the dural blood vessels on the brain's surface, it causes dilation. It also causes the release of brain chemicals called neuropeptides (substance P, CGRP or calcitonin gene-related peptide, neurokinin A, 5HT or serotonin, and noradrenalin.)
The release of these chemicals causes inflammation, and what is called peripheral sensitization. This is most likely what results in the throbbing pain most people experience. As the attack progresses, something can occur called central sensitization. When this occurs, it causes what is known as cutaneous allodynia. This means that things that are usually just a normal touch are now felt as painful. Many headache patients with allodynia cannot continue to wear earrings, necklaces, or their glasses. Some find that they cannot lie down on the side of the head pain, or report that "even their hair hurts." Up to 80% of migraine sufferers are affected by some degree of cutaneous allodynia, and it generally occurs in the late stages of a migraine attack when the pain is severe. This is why it is important to treat early when the pain is mild or moderate.
When central sensitization becomes advanced, it can involve areas beyond the head, and simple touch on the arms or shoulder can be perceived as painful. For example, I am aware of one migraine sufferer who is bothered by the seams in her clothing during such an attack. At this stage of the migraine, migraine-specific medication is less likely to be helpful, and studies have shown that while they will reduce the pain and relieve the throbbing, they cannot abort the attack, and allodynic pain remains as well as other migraine symptoms.
In late-stage migraine, other medications may be necessary in order to end the attack. We do not yet have migraine-specific medications designed for the late stage of the migraine attack, although research into migraine pathophysiology is ongoing. As we learn more, it should lead to better developments in the treatment of migraine.
