The mechanisms underlying chronic migraine are unresolved, but are hypothesized to involve a degree of inflammation.1 At a session titled “Inflammation and migraine” during the 19th Congress of the International Headache Society (IHC), Prof. Jean Schoenen (University of Liège, Belgium) provided an overview of the clinical evidence for the role of inflammation in migraine. Following Prof. Schoenen’s presentation, Prof. Turgay Dalkara (Hacettepe University, Turkey) discussed the inflammasome story in relation to migraine.
“Sleep deprivation is a complex thing. I believe it does many things in the brain that predisposes us to migraine attack.”
– Prof. Turgay Dalkara (Hacettepe University, Turkey)
Clinical evidence for the role of inflammation and anti-inflammatory drugs in migraine
Prof. Schoenen stated that molecular markers, imaging studies, sensitization of nociceptors, and the effect of non-steroidal anti-inflammatory drugs (NSAIDs) provide clinical evidence of neurogenic inflammation in migraine. Changes in the levels of inflammatory markers – including cytokines and cyclooxygenase-2 – have been shown during migraine attacks.2,3 However, the relevance of these changes to migraine pathophysiology is unclear and requires further research.
Although imaging studies show no disruption to the blood–brain barrier during migraine attacks with or without aura,4,5 results of a recent imaging study showed neuroinflammation in the visual cortex and nociceptive processing areas in migraine with aura.6 In Prof. Schoenen’s experience, NSAIDs are almost as effective as oral triptans for the treatment of mild/moderate migraine. However, this does not prove the role of inflammation in migraine, as NSAIDs can also have central effects.
Prof. Schoenen concluded his presentation by agreeing with a proposal by Prof. Lars Edvinsson and his colleagues in a recent review, which states that chronic migraine involves neurogenic neuroinflammation in the trigeminovascular system.1
The inflammasome story and migraine
Prof. Dalkara described a signaling pathway between stressed neurons and meningeal trigeminal afferents, which may explain how migraine headaches are generated.7 According to Prof. Dalkara, a single cortical spreading depression (CSD) triggers a sequence of inflammatory signaling in the parenchyma. This leads to a sustained release of cytokines, prostanoids and nitric oxide from glia limitans that activates trigeminal nociceptors around glia vessels. This pathway may trigger headache when neurons are stressed.7
Prof. Dalkara explained that migraine triggers such as sleep deprivation can induce excitatory synaptic stress by reducing availability of glycogen-derived glucose and lowering the threshold for CSD induction.8 Prof. Dalkara also highlighted in the conclusion of his presentation that prolonged activity in the locus coeruleus reduces the glycogen availability required during prolonged excitatory transmission.
Edvinsson L, et al. Does inflammation have a role in migraine? Nat Rev Neurol 2019;15:483–490.
Sarchielli P, et al. Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache 2006;46:200–207.
Li C, et al. Plasma Levels of Cyclooxygenase-2 (COX-2) and Visfatin During Different Stages and Different Subtypes of Migraine Headaches. Med Sci Monit 2017;23:24–28.
Hougaard A, et al. Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. Brain;2017;140:1633–1642.
Amin FM, et al. Intact blood-brain barrier during spontaneous attacks of migraine without aura: a 3T DCE-MRI study. Eur J Neurol 2017;24:1116–1124.
Albrecht DS, et al. Imaging of neuroinflammation in migraine with aura: A [11C]PBR28 PET/MRI study. Neurology 2019;92:e2038-e2050.
Karatas H, et al. Spreading depression triggers headache by activating neuronal Panx1 channels. Science 2013;339:1092–1095.
Kilic K, et al. Inadequate brain glycogen or sleep increases spreading depression susceptibility. Ann Neurol 2018;83:61–73.