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?
Biomarkers
CGRP
Detoxification
Headache
Medication overuse
MicroRNA
Migraine
Pain
Journal
The journal of headache and pain
ISSN: 1129-2377
Titre abrégé: J Headache Pain
Pays: England
ID NLM: 100940562
Informations de publication
Date de publication:
16 Oct 2020
16 Oct 2020
Historique:
received:
18
07
2020
accepted:
02
10
2020
entrez:
17
10
2020
pubmed:
18
10
2020
medline:
22
12
2020
Statut:
epublish
Résumé
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. We evaluated the plasma levels of calcitonin gene-related peptide (CGRP) and the expression of miR-34a-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. 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. Our findings identify a potential panel of peripheral markers associated with migraine subtypes and disease severity. CGRP levels as well as miRNAs expression were influenced by MO, and modulated by detoxification in subjects with CM-MO. The study protocol was registered at www.clinicaltrials.gov ( NCT04473976 ).
Sections du résumé
BACKGROUND
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
METHODS
We evaluated the plasma levels of calcitonin gene-related peptide (CGRP) and the expression of miR-34a-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
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.
CONCLUSIONS
CONCLUSIONS
Our findings identify a potential panel of peripheral markers associated with migraine subtypes and disease severity. CGRP levels as well as miRNAs expression were influenced by MO, and modulated by detoxification in subjects with CM-MO.
TRIAL REGISTRATION
BACKGROUND
The study protocol was registered at www.clinicaltrials.gov ( NCT04473976 ).
Identifiants
pubmed: 33066724
doi: 10.1186/s10194-020-01189-0
pii: 10.1186/s10194-020-01189-0
pmc: PMC7565351
doi:
Substances chimiques
Biomarkers
0
MicroRNAs
0
Calcitonin
9007-12-9
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Banques de données
ClinicalTrials.gov
['NCT04473976']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
122Subventions
Organisme : Ministero della Salute
ID : GR-2016-02363848, and RC2017-2019
Références
Cephalalgia. 2018 Jan;38(1):1-211
pubmed: 29368949
Curr Opin Neurol. 2017 Jun;30(3):281-286
pubmed: 28234796
Mol Psychiatry. 2011 Dec;16(12):1159-68
pubmed: 21606928
Curr Opin Neurol. 2011 Jun;24(3):193-6
pubmed: 21467931
Ann Neurol. 2010 Mar;67(3):325-37
pubmed: 20373344
Neurology. 2013 Oct 1;81(14):1191-6
pubmed: 23975872
J Headache Pain. 2017 Oct 4;18(1):101
pubmed: 28980171
Mol Diagn Ther. 2019 Dec;23(6):681-694
pubmed: 31612314
Headache. 2012 Oct;52(9):1350-61
pubmed: 22670561
Acta Neurol Scand. 2019 Mar;139(3):269-275
pubmed: 30457160
Annu Rev Pharmacol Toxicol. 2015;55:533-52
pubmed: 25340934
Peptides. 2019 Jun;116:16-21
pubmed: 31018157
Mol Neurobiol. 2016 Apr;53(3):1494-1500
pubmed: 25636687
Headache. 2020 Jun;60(6):1132-1164
pubmed: 32293721
Curr Med Chem. 2019;26(34):6191-6206
pubmed: 29932027
J Headache Pain. 2018 Jul 13;19(1):53
pubmed: 30006780
Neurobiol Dis. 2014 Nov;71:159-68
pubmed: 25119878
Cephalalgia. 2020 Oct;40(12):1336-1345
pubmed: 32715736
Lancet Neurol. 2019 Sep;18(9):891-902
pubmed: 31174999
Cephalalgia. 2020 Apr;40(5):503-516
pubmed: 31635478
Cephalalgia. 2018 Apr;38(5):815-832
pubmed: 29504482
Mol Med Rep. 2017 Dec;16(6):9367-9374
pubmed: 29039515
Microrna. 2017;6(1):17-21
pubmed: 28056747
Front Neurol. 2019 Jan 24;10:10
pubmed: 30733702
J Headache Pain. 2020 Jun 5;21(1):65
pubmed: 32503421
J Headache Pain. 2018 Mar 12;19(1):22
pubmed: 29532195
Expert Opin Emerg Drugs. 2018 Dec;23(4):301-318
pubmed: 30484333
Cephalalgia. 2020 Sep 23;:333102420949201
pubmed: 32967434
Cephalalgia. 2014 Feb 20;34(9):645-655
pubmed: 24558185
Cephalalgia. 2011 May;31(7):851-60
pubmed: 21444643
J Headache Pain. 2013 Feb 08;14:10
pubmed: 23565591