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Why is migraine pain long-lasting and throbbing?

The doctoral thesis of Nikita Mikhailov, MSc, addresses several key mechanisms behind migraine pain at its origin site – in the meninges covering brain. By using animal models, he explored the mechanisms underlying two main features of migraine pain, namely its long-lasting character and throbbing nature. Moreover, the thesis describes for the first time the impact of recently discovered meningeal lymphatic system on markers of migraine state. The public examination of the doctoral thesis will be held in English online on 4 September 2020 starting at 12 noon.

Migraine is one of the most common neurological disorders affecting up to 15% of the general population. In Finland, 16.000 migraine attacks occur every day. Notably, migraine affects mostly young and middle-aged socially and economically active people. Every year in Finland, migraine accounts for 2 million absentee workdays and 300 million euro losses.

First part of the doctoral thesis demonstrated that the neurotransmitter acetylcholine implicated in the so-called trigemino-parasympathetic reflex, provides a sustained activation of somatic meningeal afferents. Acetylcholine stable analogues activated immune mast cells as drivers of further neuroinflammation and activation of nerve terminals. These mechanisms can contribute together to the long-lasting migraine pain.

Second part of the study showed that recently discovered mechanosensitive Piezo1 receptors can generate nociceptive firing of trigeminal nerve terminals suggesting a novel molecular mechanism of migraine pain. “Blood vessel pulsation in meninges can be a trigger for these Piezo receptors, and can underlie the mechanism of throbbing pain, well-known to patients,” Mikhailov says.

Third part of the study explored the role of meningeal lymphatic system proposed to drain this key region from metabolites. In a transgenic mouse model lacking the meningeal lymphatic vessels, Mikhailov found a new balance between multiple humoral and cellular migraine-provoking and preventing factors with the prevalence of the anti-inflammatory mechanisms.

“Taken together, these newly discovered mechanisms provide all-round details helping to crush migraine in the bud, in its origin site, in meninges,” Mikhailov concludes.

The doctoral thesis of Nikita Mikhailov, Master of Science, entitled The role of cholinergic and mechanosensitive signalling and the meningeal lymphatic system in peripheral trigeminal nociception, will be examined at the Faculty of Health Sciences. The opponent in the public examination will be Professor Antti Pertovaara of the University of Helsinki and the Custos will be Professor Rashid Giniatullin of the University of Eastern Finland.

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Mikhailov, Nikita. The role of cholinergic and mechanosensitive signalling and the meningeal lymphatic system in peripheral trigeminal nociception