Plasma levels of CGRP and expression of specific microRNAs in blood cells of episodic and chronic migraine subjects: tow

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(2020) 21:122

The Journal of Headache and Pain

RESEARCH ARTICLE

Open Access

Plasma levels of CGRP and expression of specific microRNAs in blood cells of episodic and chronic migraine subjects: towards the identification of a panel of peripheral biomarkers of migraine? Rosaria Greco1†, Roberto De Icco1,2*† , Chiara Demartini1, Anna Maria Zanaboni1,2, Elena Tumelero1, Grazia Sances1, Marta Allena1 and Cristina Tassorelli1,2

Abstract Background: Migraine can manifest with an episodic or a chronic pattern in a continuum of disease severity. Multiple factors are associated with the progression of the pattern from episodic to chronic. One of the most consistently reported factors is the overuse of medications (MO) for the acute treatment of migraine attacks. The mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) are elusive. In order to provide insights into these mechanisms, the present study aims to identify possible peripheral biomarkers associated with the two forms of migraine, and with the presence of MO. Methods: We evaluated the plasma levels of calcitonin gene-related peptide (CGRP) and the expression of miR34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with EM (n = 27) or CM-MO (n = 28). Subjects in the CM-MO group were also tested 2 months after an in-hospital detoxification protocol. Results: CGRP, miR-382-5p, and miR-34a-5p levels were significantly higher in CM-MO subjects when compared to EM patients (p = 0.003 for all comparisons). After correcting for age, sex, and disease duration, miRNAs expression was still significantly associated with migraine phenotype (EM vs. CM-MO: p = 0.014 for miR-382-5p, p = 0.038 for miR-34a-5p), while CGRP levels were not (p = 0.115). CGRP plasma levels significantly and positively correlated with miR-382-5p (Spearman’s rho: 0.491, p = 0.001) and miR-34a-5p (Spearman’s rho: 0.303, p =0.025) in the overall population. In the CM-MO group, detoxification significantly decreased CGRP levels and miRNAs expression (p = 0.001). When comparing responders and non-responders to the detoxification, the former group (n = 23) showed significantly higher levels of CGRP at baseline, and significantly lower expression of miR-382-5p after the detoxification. (Continued on next page)

* Correspondence: [email protected] † Rosaria Greco and Roberto De Icco contributed equally to this work. 1 Headache Science & Neurorehabilitation, IRCCS Mondino Foundation, Pavia, Italy 2 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the ar