The site of migraine pain resides in the peripheral nervous system. It is the conclusion of a study coordinated by a group of scientists from the Clinical Pharmacology Section of the University of Florence and of the Headache Center of the Careggi University Hospital published in Nature Communications ("Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice" - DOI 10.1038 / s41467-022-28204-z).
Migraine affects about one billion and two hundred million people, mostly women aged 15 to 50, who experience this condition with a sharp reduction in the quality of their working, family and emotional life, so much so that the World Health Organization (WHO) called migraine the most disabling disease in that age group. For two thousand years the mystery of why so many patients were afflicted with recurrent and disabling pain attacks remained unsolved until two years ago when drugs were introduced that block the CGRP (calcitonin gene related peptide) or its receptor. In particular, the monoclonal antibodies that block the action of CGRP have proved to be effective and very safe drugs for preventing migraine attacks.
The prevailing idea that the enigmatic migraine pain originates in the central nervous system has been challenged by the fact that monoclonal antibodies do not penetrate the brain, and therefore this organ cannot be the site of migraine pain. However, the mystery of where and how migraine pain is generated remained unsolved.
A group of scientists led by Pierangelo Geppetti, Romina Nassini and Francesco De Logu in collaboration with an international team (New York University and Monash University, Melbourne) published in Nature Communications the discovery that the CGRP released from the nerve fibers of the trigeminal nerve activates its receptor in Schwann cells. Schwann cells, until now considered little more than a protective glove or passive support for the nerves they surround, have instead proved to be fundamental elements in generating the intense, pounding and prolonged pain of migraines. CGRP penetrates inside the Schwann cell (a bit like coronavirus does in lung cells) where by activating complex intracellular mechanisms it induces a marked hypersensitivity of the cranial pain nerves that can last for hours or days, just like in migraines.
Although the Headache Centers have taken on a large number of treatments with anti-CGRP monoclonal antibodies with very positive results, about 30% of patients fail to benefit from these specific and innovative treatments. Therefore the Italian, American and Australian scientists have tried to improve the anti-CGRP therapy of migraine, and report in their study a new nanomedicine which, penetrating inside the Schwann cell, has proved to be more active than conventional ones in reducing the pain produced by CGRP. The study funded by the European Research Council therefore opens up a new and important perspective to be able to treat even those migraine patients who do not respond to current treatments.
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