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What happens in the brain and meninges during a migraine attack?
Understanding the relationships between brain activation and migraine symptoms is fundamental to instituting appropriate management and pharmacologic therapy, said Dr Andrew Blumenthal, Director, Headache Centre of Southern California, at AAN 2021. The prodrome and aura are linked to activation of different areas of the brain. The incapacitating throbbing headache is linked to activation of the trigeminovascular system and the release of calcitonin-gene-related peptide in the meninges.
Chronic migraine affects nearly 1% of the US population,1 said Dr Blumenthal, and each episode may last up to 7 days.2 Its high prevalence and disabling nature together with the lack of effective preventive therapy have led to its position as the second leading cause of years lost to disability worldwide.3
Migraine is a common disabling primary headache disorder
Multiple areas of the brain are involved in the early phases of migraine
The prodrome starts in the hypothalamus and precedes the headache by up to a few days. Patients have a premonition that something bad is going to happen and may experience fatigue, neck discomfort, food cravings and gastrointestinal disturbances.2
A migraine episode starts in the hypothalamus
A subsequent wave of electrical depression over the cortical surface of the brain is associated with transient neurologic deficits. These last from 5–60 minutes and characterise a migraine aura.2,4
Only about 20–30% of patients experience aura,2 said Dr Blumenthal, and it is typically visual, with a blind spot that slowly expands.5
Migraine aura is associated with a wave of cortical electrical depression
Other symptoms that might occur during an aura include numbness that creeps up the arm and into the face, trouble finding words, vertigo, and tinnitus.5
What causes the pain in the headache phase?
Most of the pain is felt in the meninges
Activation of the trigeminal nucleus caudalis and the superior salivatory nucleus in the brain stem are associated with the headache,2 said Dr Blumenthal. These nuclei feed to the trigeminal ganglion and the sphenopalatine ganglion, respectively, and these in turn project nerve endings (nociceptors) to the blood vessels in the meninges.2
The main mediator released by the nociceptors, particularly the trigeminal, is calcitonin-gene-related peptide (CGRP).6 CGRP is a potent vasodilator and causes inflammation around the blood vessels,6 resulting in the incapacitating throbbing headache,2 explained Dr Blumenthal. If the pain is not effectively treated, the inflammation will continue, creating increasing amounts of CGRP.2
It is well established that CGRP is implicated in migraine pathophysiology
Dr Blumenthal highlighted the following evidence demonstrating the close association of CGRP with migraine episodes:
- High CGRP levels can be measured during a migraine in the venous drainage of the brain7
- If a patient is treated and the migraine resolves, the CGRP levels fall8
- Infusing a patient with CGRP can trigger an attack9
The satellite symposium was sponsored by AbbVie, Inc.
Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.
References
- Buse D, et al. Headache impact of chronic and episodic migraine: results from the American Migraine Prevalence and Prevention study. Headache 2012;52:3–17.
- Goadsby PJ, et al. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 2017;97:553–622.
- GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390:1211–59.
- Bolay H, et al. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 2002;8:136–42.
- Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1–211.
- Iyengar S, et al. CGRP and the trigeminal system in migraine. Headache 2019;59:659–81.
- Goadsby PJ, et al. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990;28:183–7.
- Cernuda-Morollón E, et al. OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine. Pain 2015;156:820–4.
- Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-likeattacks in patients with migraine with aura. Cephalalgia 2010;30:1179–1186.