Epigenetic mechanisms in migraine: a promising avenue?

Eising, Else; Datson, Nicole A.; Maagdenberg, Arn M. J. M. van den; Ferrari, Michel D.

doi:10.1186/1741-7015-11-26

Cited by 92 publications

(100 citation statements)

References 60 publications

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“…Epigenetics is defined as the regulation of gene expression in the absence of changes in DNA sequence and has also been considered in the context of migraine (148). Examples of epigenetic genes that may regulate CGRP would be genes encoding transcription factors that bind the CGRP gene enhancer or enzymes that modify chromatin structure.…”

Section: Future Directions: Epistatic Partners and Epigenetic Regulatmentioning

confidence: 99%

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Russo

2015

Annu. Rev. Pharmacol. Toxicol.

309

299

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Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The neuropeptide calcitonin gene-related peptide (CGRP) is now firmly established as a key player in migraine. Clinical trials carried out during the past decade have proved that CGRP receptor antagonists are effective for treating migraine, and antibodies to the receptor and CGRP are currently under investigation. Despite this progress in the clinical arena, the mechanisms by which CGRP triggers migraine remain uncertain. This review discusses mechanisms whereby CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Future studies on epistatic and epigenetic regulators of CGRP actions are expected to shed further light on CGRP actions in migraine. In conclusion, targeting CGRP represents an approachable therapeutic strategy for migraine.

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Section: Future Directions: Epistatic Partners and Epigenetic Regulatmentioning

confidence: 99%

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Russo

2015

Annu. Rev. Pharmacol. Toxicol.

309

299

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“…The pathophysiology of migraine is unclear, but several studies have demonstrated abnormalities in pain-processing mechanisms 1. In addition, inflammation has long been suggested to play a role in migraine 2. Various vasoactive neuropeptides have been released from trigeminal and parasympathetic perivascular fibers during neurogenic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case–control study

Coşkun¹,

Varol

Özdemir

et al. 2016

NDT

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Migraine pathogenesis involves a complex interaction between hormones, neurotransmitters, and inflammatory pathways, which also influence the migraine phenotype. The Mediterranean fever gene (MEFV) encodes the pyrin protein. The major role of pyrin appears to be in the regulation of inflammation activity and the processing of the cytokine pro-interleukin-1β, and this cytokine plays a part in migraine pathogenesis. This study included 220 migraine patients and 228 healthy controls. Eight common missense mutations of the MEFV gene, known as M694V, M694I, M680I, V726A, R761H, K695R, P369S, and E148Q, were genotyped using real-time polymerase chain reaction with 5′ nuclease assays, which include sequence specific primers, and probes with a reporter dye. When mutations were evaluated separately among the patient and control groups, only the heterozygote E148Q carrier was found to be significantly higher in the control group than in the patient group (P=0.029, odds ratio [95% confidence interval] =0.45 [0.21–0.94]). In addition, the frequency of the homozygote and the compound heterozygote genotype carrier was found to be significantly higher in patients (n=8, 3.6%) than in the control group (n=1, 0.4%) (P=0.016, odds ratio [95% confidence interval] =8.57 [1.06–69.07]). However, there was no statistically significant difference in the allele frequencies of MEFV mutations between the patients and the healthy control group (P=0.964). In conclusion, the results of the present study suggest that biallelic mutations in the MEFV gene could be associated with a risk of migraine in the Turkish population. Moreover, MEFV mutations could be related to increased frequency and short durations of migraine attacks (P=0.043 and P=0.021, respectively). Future studies in larger groups and expression analysis of MEFV are required to clarify the role of the MEFV gene in migraine susceptibility.

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“…Several lines of evidence now attest that inflammation plays a crucial role in the pathogenesis of migraine, wherein a number of proinflammatory cytokines are actively released during migraine and are then involved in a complex process of sensitization of nerve endings in meninges, thus promoting or amplifying the feeling of pain [6]. It has also been recently shown that the risk of cardiovascular disease is substantially increased in patients with migraine.…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein and migraine. Facts or speculations?

Lippi¹,

Mattiuzzi²,

Cervellin

2014

Clinical Chemistry and Laboratory Medicine

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Migraine is a highly prevalent and frequently disabling disorder. Since the pathogenesis of this condition has a strong inflammatory component and migraine is significantly associated with cardiovascular disease, we assess whether C-reactive protein (CRP) may be epidemiologically or casually linked with migraine. An electronic search on Medline, Scopus and Web of Science produced 17 studies reporting original data about the epidemiological association between CRP and migraine (1 retrospective, 1 interventional, 14 cross-sectional and 1 both interventional and cross-sectional). When all studies reporting sufficient data about CRP values were pooled (n = 12; 6980 cases and 38,975 controls), the concentration of CRP was found to be significantly higher in patients with migraine than in controls (weighted mean difference 1.12 mg/L; 95% CI 1.01-1.25 mg/L; p < 0.001). In further analysis of studies containing separate data for migraine with and without aura (n = 7), CRP values remained significantly higher in both migraineur patients with aura (n = 1939; weighted mean difference 0.88 mg/L; 95% CI 0.63-1.14 mg/L; p < 0.001) or without aura (n = 2483; weighted mean difference 1.04 mg/L; 95% CI 0.78-1.30 mg/L; p < 0.001) when compared with controls (n = 29,354). Despite a large interstudy heterogeneity (99.3%), our analysis provides evidence of a potential epidemiological association between increased concentration of CRP and migraine, thus paving the way for further clinical investigations about therapeutic agents that may contextually decrease the risk of cardiovascular disease and reduce the burden of migraine.

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Epigenetic mechanisms in migraine: a promising avenue?

Cited by 92 publications

References 60 publications

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case–control study

C-reactive protein and migraine. Facts or speculations?

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Epigenetic mechanisms in migraine: a promising avenue?

Cited by 92 publications

References 60 publications

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case&ndash;control study

C-reactive protein and migraine. Facts or speculations?

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Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case–control study