Blueprint of a migraine
A migraine attack comprises several phases, of which the headache is just one: other symptoms, such as fatigue and muscle stiffness, can precede the headache by several days and linger after it has passed. Some people also experience neurological disturbances known as aura. The mechanisms behind pain and aura are not certain, but theories abound.
A painful pathway
The headache phase can last between 4 and 72 hours. It is characterized by pulsing or throbbing pain on one or both sides of the head, nausea and vomiting, and sensitivity to light, sound, smell and touch. The leading theory of migraine is that headache is the result of activation of the trigeminovascular system, the network of nerves linked to blood vessels in the head.
Symptoms include seeing lights or shapes, vision loss and prickling sensations in an arm or leg. They develop over 15–20 minutes and last less than an hour.
It is widely thought that auras are caused by a slow-moving wave of depolarization that passes through the brain, known as cortical spreading depression (CSD).
Drugs are not the only choice for treating migraine, but there are numerous options available, including over-the-counter non-steroidal anti-inflammatory drugs, opioids and monoclonal antibodies. They work by various mechanisms, not all of which are completely understood, to interrupt the pain.
Tryptamine-based drugs were introduced in the 1990s. They mimic the activity of the neurotransmitter serotonin (5-HT) and are effective in the early stages of an attack. At 5-HT1B receptors, they reduce pain by causing cranial blood vessels to constrict. At 5-HT1D receptors, they block the release of neuropeptides that trigger inflammation.
Monoclonal antibodies against CGRP, first approved in 2019, are given by injection to prevent migraine attacks. The antibodies bind to either CGRP or its receptor to stop the peptide from dilating blood vessels and increasing inflammation in the meninges. They also block the transmission of pain along the trigeminal pathway.
Onabotulinumtoxin A, or Botox, is a neurotoxin that was approved for use in chronic migraine in the United States in 2010. It is given by injection and can prevent attacks for up to 90 days. Botox interferes with the neurotransmitter acetylcholine (ACh) by breaking a protein required for its release at a synapse. This prevents ACh from activating pain-receptor fibres in the brain.
Migraine and its cousins
Migraine is a major category of headache, but it is not the only type. Tension headaches are more common, yet generally less painful, whereas cluster headaches are excruciatingly painful but fortunately rare.
Nature 586, S2-S3 (2020)