Title:Novelty in Inflammation and Immunomodulation in Migraine
Volume: 25
Issue: 27
Author(s): Cinzia Cavestro*, Marcella Ferrero, Silvia Mandrino, Marco Di Tavi and Eugenia Rota
Affiliation:
- Department of Neurology, Headache Centre, ASL CN2, Alba,Italy
Keywords:
Inflammation, neuroinflammation, immunomodulation, migraine, CGRP, botulinum toxin, monoclonal antibodies anti-CGRP.
Abstract:
Background: Migraine is a diffuse and disabling disease. Its pathophysiology is complex and involves
both central and peripheral dysfunctions.
Objective: This review will discuss the pathogenesis of migraine from the origin of the neuro-inflammatory theory,
to the modern pathophysiological model and the latest therapies.
Methods: PUBMED and EMBASE (up to May 2019) were searched for: migraine, inflammation, immunomodulation.
An additional search was carried out from the bibliography of previous review articles.
Results: Migraine was thought to be mainly a vascular disorder, according to the so-called “vascular theory”.
Based on animal models, a new hypothesis called “the neuro-inflammatory” was conceived at the end of the 20th
century. The growing knowledge about the trigeminovascular system and its role in the inflammatory-pain pathway,
allowed to identify other specific neurotransmitters, such as the Calcitonin Gene-Related Peptide and Pituitary
Adenylate Cyclase-Activating Peptide. Evidence was provided that the inflammatory-pain system could
become sensitised and, due to this sensitisation, the pain could also perpetuate, even in the absence of any triggers
of the migraine attack. At last, brain immune cells modification during cortical spreading depression in migraine
was demonstrated, along with the existence and function of the glymphatic system. The better comprehension of
the immune system abnormalities allowed the development of new immunomodulating drugs: the monoclonal
antibodies against the CGRP or the CGRP receptor. Moreover, new insights into the molecular mechanism of
CGRP, and the function of C-fibres and Aδ-fibres, highlighted the mechanism of action of Botulinum Toxin type
A in the treatment of chronic migraine.