{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:01:05Z","timestamp":1788184865142,"version":"build-2803163510"},"reference-count":207,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2019-01066"],"award-info":[{"award-number":["2019-01066"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Migraine is a complex neurological disorder and a major cause of disability. A wide range of different drug classes such as triptans, antidepressants, anticonvulsants, analgesics, and beta-blockers are used in acute and preventive migraine therapy. Despite a considerable progress in the development of novel and targeted therapeutic interventions during recent years, e.g., drugs that inhibit the calcitonin gene-related peptide (CGRP) pathway, therapy success rates are still unsatisfactory. The diversity of drug classes used in migraine therapy partly reflects the limited perception of migraine pathophysiology. Genetics seems to explain only to a minor extent the susceptibility and pathophysiological aspects of migraine. While the role of genetics in migraine has been extensively studied in the past, the interest in studying the role of gene regulatory mechanisms in migraine pathophysiology is recently evolving. A better understanding of the causes and consequences of migraine-associated epigenetic changes could help to better understand migraine risk, pathogenesis, development, course, diagnosis, and prognosis. Additionally, it could be a promising avenue to discover new therapeutic targets for migraine treatment and monitoring. In this review, we summarize the state of the art regarding epigenetic findings in relation to migraine pathogenesis and potential therapeutic targets, with a focus on DNA methylation, histone acetylation, and microRNA-dependent regulation. Several genes and their methylation patterns such as CALCA (migraine symptoms and age of migraine onset), RAMP1, NPTX2, and SH2D5 (migraine chronification) and microRNA molecules such as miR-34a-5p and miR-382-5p (treatment response) seem especially worthy of further study regarding their role in migraine pathogenesis, course, and therapy. Additionally, changes in genes including COMT, GIT2, ZNF234, and SOCS1 have been linked to migraine progression to medication overuse headache (MOH), and several microRNA molecules such as let-7a-5p, let-7b-5p, let-7f-5p, miR-155, miR-126, let-7g, hsa-miR-34a-5p, hsa-miR-375, miR-181a, let-7b, miR-22, and miR-155-5p have been implicated with migraine pathophysiology. Epigenetic changes could be a potential tool for a better understanding of migraine pathophysiology and the identification of new therapeutic possibilities. However, further studies with larger sample sizes are needed to verify these early findings and to be able to establish epigenetic targets as disease predictors or therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms24119127","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T08:14:28Z","timestamp":1684829668000},"page":"9127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The Epigenetics of Migraine"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9964-8960","authenticated-orcid":false,"given":"Farzin","family":"Zobdeh","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Husargatan 3, P.O. Box 593, 75124 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1335-2393","authenticated-orcid":false,"given":"Ivan I.","family":"Eremenko","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Husargatan 3, P.O. Box 593, 75124 Uppsala, Sweden"},{"name":"Advanced Molecular Technology, LLC, 354340 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-4728","authenticated-orcid":false,"given":"Mikail A.","family":"Akan","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Husargatan 3, P.O. Box 593, 75124 Uppsala, Sweden"},{"name":"Advanced Molecular Technology, LLC, 354340 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim V.","family":"Tarasov","sequence":"additional","affiliation":[{"name":"Advanced Molecular Technology, LLC, 354340 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7047-1436","authenticated-orcid":false,"given":"Vladimir N.","family":"Chubarev","sequence":"additional","affiliation":[{"name":"Advanced Molecular Technology, LLC, 354340 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helgi B.","family":"Schi\u00f6th","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Husargatan 3, P.O. Box 593, 75124 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Mwinyi","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Husargatan 3, P.O. Box 593, 75124 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S0140-6736(17)32154-2","article-title":"Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 328 Diseases and Injuries for 195 Countries, 1990\u20132016: A Systematic Analysis for the Global Burden of Disease Study 2016","volume":"390","author":"Vos","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache Classification Committee of the International Headache Society (IHS) the International Classification of Headache Disorders, 3rd Edition","volume":"38","author":"Arnold","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_3","first-page":"415","article-title":"Is the management of migraine and tension headache in Croatia satisfactory?","volume":"67","year":"2013","journal-title":"Acta Med. Croat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E153","DOI":"10.1503\/cmaj.211969","article-title":"Diagnosis and Acute Management of Migraine","volume":"195","author":"Tzankova","year":"2023","journal-title":"CMAJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1111\/bph.15657","article-title":"Pharmacological Treatment of Migraine: Drug Classes, Mechanisms of Action, Clinical Trials and New Treatments","volume":"178","author":"Zobdeh","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s13311-018-0621-8","article-title":"Current Prophylactic Medications for Migraine and Their Potential Mechanisms of Action","volume":"15","author":"Sprenger","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6619","DOI":"10.1523\/JNEUROSCI.0373-15.2015","article-title":"Migraine: Multiple Processes, Complex Pathophysiology","volume":"35","author":"Burstein","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s10194-016-0689-7","article-title":"Characterising the Premonitory Stage of Migraine in Children: A Clinic-Based Study of 100 Patients in a Specialist Headache Service","volume":"17","author":"Karsan","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1212\/01.WNL.0000052998.58526.A9","article-title":"Premonitory Symptoms in Migraine: An Electronic Diary Study","volume":"60","author":"Giffin","year":"2003","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1046\/j.1468-2982.1996.1604239.x","article-title":"Migraine without Aura and Migraine with Aura Are Distinct Clinical Entities: A Study of Four Hundred and Eighty-Four Male and Female Migraineurs from the General Population","volume":"16","author":"Russell","year":"1996","journal-title":"Cephalalgia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev-physiol-030212-183717","article-title":"Pathophysiology of Migraine","volume":"75","author":"Pietrobon","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1152\/jn.1945.8.1.33","article-title":"Propagation of spreading cortical depression","volume":"8","author":"Leo","year":"1945","journal-title":"J. Neurophysiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s10194-019-1001-4","article-title":"Spreading Depression as a Preclinical Model of Migraine","volume":"20","author":"Harriott","year":"2019","journal-title":"J. Headache Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of Migraine: A Disorder of Sensory Processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/j.1468-2982.2006.01157.x","article-title":"Premonitory and Resolution Symptoms in Migraine: A Prospective Study in 100 Unselected Patients","volume":"26","author":"Quintela","year":"2006","journal-title":"Cephalalgia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1212\/WNL.43.7.1369","article-title":"Familial Occurrence of Migraine without Aura and Migraine with Aura","volume":"43","author":"Russell","year":"1993","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/ng.3285","article-title":"Meta-Analysis of the Heritability of Human Traits Based on Fifty Years of Twin Studies","volume":"47","author":"Polderman","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00439-017-1816-5","article-title":"A Genetic Risk Score Is Differentially Associated with Migraine with and without Aura","volume":"136","author":"Pisanu","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s10194-019-1017-9","article-title":"Advances in Genetics of Migraine","volume":"20","author":"Sutherland","year":"2019","journal-title":"J. Headache Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S1474-4422(11)70048-5","article-title":"Sporadic and Familial Hemiplegic Migraine: Pathophysiological Mechanisms, Clinical Characteristics, Diagnosis, and Management","volume":"10","author":"Russell","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/dmcn.13744","article-title":"Phenotypes, Genotypes, and the Management of Paroxysmal Movement Disorders","volume":"60","author":"Kovac","year":"2018","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/nm.2216","article-title":"A Dominant-Negative Mutation in the TRESK Potassium Channel Is Linked to Familial Migraine with Aura","volume":"16","author":"Cader","year":"2010","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fila, M., Sobczuk, A., Pawlowska, E., and Blasiak, J. (2022). Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116151"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Carvalho, E., Dias, A., Sousa, A., Lopes, A.M., Martins, S., Pinto, N., Lemos, C., and Alves-Ferreira, M. (2022). A High Methylation Level of a Novel \u2212284 Bp CpG Island in the RAMP1 Gene Promoter Is Potentially Associated with Migraine in Women. Brain Sci., 12.","DOI":"10.3390\/brainsci12050526"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1177\/0333102410391487","article-title":"Epigenetic Regulation of the Calcitonin Gene\u2013Related Peptide Gene in Trigeminal Glia","volume":"31","author":"Park","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s10194-020-01189-0","article-title":"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?","volume":"21","author":"Greco","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nature05913","article-title":"Perceptions of Epigenetics","volume":"447","author":"Bird","year":"2007","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24R","DOI":"10.1203\/pdr.0b013e3180457684","article-title":"Epigenetics and MicroRNAs","volume":"61","author":"Chuang","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1242\/jeb.107318","article-title":"Dynamics of Epigenetic Phenomena: Intergenerational and Intragenerational Phenotype \u2018Washout\u2019","volume":"218","author":"Burggren","year":"2015","journal-title":"J. Exp. Biol."},{"key":"ref_30","first-page":"808","article-title":"Methylation of the HMLH1 Promoter Correlates with Lack of Expression of HMLH1 in Sporadic Colon Tumors and Mismatch Repair-Defective Human Tumor Cell Lines","volume":"57","author":"Kane","year":"1997","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1136\/jmg.30.5.410","article-title":"Guidelines for the Diagnosis of Fragile X Syndrome. National Fragile X Foundation","volume":"30","author":"Oostra","year":"1993","journal-title":"J. Med. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41586-019-1411-0","article-title":"Advances in Epigenetics Link Genetics to the Environment and Disease","volume":"571","author":"Cavalli","year":"2019","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Eising, E., A Datson, N., van den Maagdenberg, A.M., and Ferrari, M.D. (2013). Epigenetic Mechanisms in Migraine: A Promising Avenue?. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-26"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1007\/s12035-015-9106-5","article-title":"Serum MicroRNA Signatures in Migraineurs During Attacks and in Pain-Free Periods","volume":"53","author":"Andersen","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target Recognition and Regulatory Functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most Mammalian MRNAs Are Conserved Targets of MicroRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D154","DOI":"10.1093\/nar\/gkm952","article-title":"MiRBase: Tools for MicroRNA Genomics","volume":"36","author":"Saini","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tcb.2014.11.004","article-title":"The Biological Functions of MiRNAs: Lessons from in Vivo Studies","volume":"25","author":"Vidigal","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s40291-019-00428-8","article-title":"Current Evidence on Potential Uses of MicroRNA Biomarkers for Migraine: From Diagnosis to Treatment","volume":"23","author":"Gazerani","year":"2019","journal-title":"Mol. Diagn. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.2174\/2211536606666170913152821","article-title":"MicroRNAs to Monitor Pain-Migraine and Drug Treatment","volume":"6","author":"Gallelli","year":"2017","journal-title":"MIRNA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Labruijere, S., Stolk, L., Verbiest, M., de Vries, R., Garrelds, I.M., Eilers, P.H.C., Danser, A.H.J., Uitterlinden, A.G., and MaassenVanDenBrink, A. (2014). Methylation of Migraine-Related Genes in Different Tissues of the Rat. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087616"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"678350","DOI":"10.3389\/fnins.2021.678350","article-title":"Using Monozygotic Twins to Dissect Common Genes in Posttraumatic Stress Disorder and Migraine","volume":"15","author":"Bainomugisa","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gerring, Z.F., McRae, A.F., Montgomery, G.W., and Nyholt, D.R. (2018). Genome-Wide DNA Methylation Profiling in Whole Blood Reveals Epigenetic Signatures Associated with Migraine. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4450-2"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1177\/0333102417690111","article-title":"Epigenetic DNA Methylation Changes Associated with Headache Chronification: A Retrospective Case-Control Study","volume":"38","author":"Winsvold","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"251581632092359","DOI":"10.1177\/2515816320923592","article-title":"Methylation Analysis of NPTX2 and SH2D5 Genes in Chronic Migraine: A Case\u2013Control Study","volume":"3","author":"Oterino","year":"2020","journal-title":"Cephalalgia Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10072-018-3348-8","article-title":"Epigenetic DNA Methylation Changes in Episodic and Chronic Migraine","volume":"39","author":"Terlizzi","year":"2018","journal-title":"Neurol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3389\/fpubh.2020.00172","article-title":"Analysis of Epigenetic Age Predictors in Pain-Related Conditions","volume":"8","author":"Kwiatkowska","year":"2020","journal-title":"Front. Public Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e63076","DOI":"10.7554\/eLife.63076","article-title":"Neuronal Complexity Is Attenuated in Preclinical Models of Migraine and Restored by HDAC6 Inhibition","volume":"10","author":"Bertels","year":"2021","journal-title":"eLife"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.bbrc.2008.09.073","article-title":"JNK1 Regulates Histone Acetylation in Trigeminal Neurons Following Chemical Stimulation","volume":"376","author":"Wu","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100089","DOI":"10.1016\/j.ynpai.2022.100089","article-title":"Analysis of the DNA Methylation Pattern of the Promoter Region of Calcitonin Gene-Related Peptide 1 Gene in Patients with Episodic Migraine: An Exploratory Case-Control Study","volume":"11","author":"Rubino","year":"2022","journal-title":"Neurobiol. Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s10194-015-0576-7","article-title":"DNA Methylation of RAMP1 Gene in Migraine: An Exploratory Analysis","volume":"16","author":"Wan","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1177\/0333102420949201","article-title":"Peripheral Changes of Endocannabinoid System Components in Episodic and Chronic Migraine Patients: A Pilot Study","volume":"41","author":"Greco","year":"2021","journal-title":"Cephalalgia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s12974-021-02342-5","article-title":"MicroRNA-155-5p Promotes Neuroinflammation and Central Sensitization via Inhibiting SIRT1 in a Nitroglycerin-Induced Chronic Migraine Mouse Model","volume":"18","author":"Wen","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s10194-022-01478-w","article-title":"Disease- and Headache-Specific MicroRNA Signatures and Their Predicted MRNA Targets in Peripheral Blood Mononuclear Cells in Migraineurs: Role of Inflammatory Signalling and Oxidative Stress","volume":"23","author":"Benczik","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fnbeh.2019.00284","article-title":"Financial Stress Interacts with CLOCK Gene to Affect Migraine","volume":"13","author":"Baksa","year":"2020","journal-title":"Front. Behav. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/ana.25965","article-title":"Circulating microRNAs Associated with Reversible Cerebral Vasoconstriction Syndrome","volume":"89","author":"Chen","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1177\/0333102417742375","article-title":"Elevated Circulating Endothelial-Specific MicroRNAs in Migraine Patients: A Pilot Study","volume":"38","author":"Cheng","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1177\/0333102420942230","article-title":"Neurophysiological and Biomolecular Effects of Erenumab in Chronic Migraine: An Open Label Study","volume":"40","author":"Fiamingo","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gallelli, L., Cione, E., Peltrone, F., Siviglia, S., Verano, A., Chirchiglia, D., Zampogna, S., Guidetti, V., Sammartino, L., and Montana, A. (2019). Hsa-MiR-34a-5p and Hsa-MiR-375 as Biomarkers for Monitoring the Effects of Drug Treatment for Migraine Pain in Children and Adolescents: A Pilot Study. JCM, 8.","DOI":"10.3390\/jcm8070928"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3109\/07853890.2015.1071871","article-title":"MicroRNA Profiling in Migraine without Aura: Pilot Study","volume":"47","author":"Tafuri","year":"2015","journal-title":"Ann. Med."},{"key":"ref_61","first-page":"2022","article-title":"MiR-30a Relieves Migraine by Degrading CALCA","volume":"22","author":"Zhai","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4710780","DOI":"10.1155\/2020\/4710780","article-title":"Differential Expression and Bioinformatic Analysis of the CircRNA Expression in Migraine Patients","volume":"2020","author":"Lin","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2014.04.001","article-title":"Epigenetics and Migraine; Complex Mitochondrial Interactions Contributing to Disease Susceptibility","volume":"543","author":"Stuart","year":"2014","journal-title":"Gene"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Fila, M., Chojnacki, C., Chojnacki, J., and Blasiak, J. (2019). Is an \u201cEpigenetic Diet\u201d for Migraines Justified? The Case of Folate and DNA Methylation. Nutrients, 11.","DOI":"10.3390\/nu11112763"},{"key":"ref_65","first-page":"289","article-title":"The Role of DNA Methylation and Histone Modifications in Transcriptional Regulation in Humans","volume":"Volume 61","author":"Kundu","year":"2013","journal-title":"Epigenetics: Development and Disease"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrg.2017.80","article-title":"The DNA Methyltransferase Family: A Versatile Toolkit for Epigenetic Regulation","volume":"19","author":"Lyko","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Younesian, S., Yousefi, A.-M., Momeny, M., Ghaffari, S.H., and Bashash, D. (2022). The DNA Methylation in Neurological Diseases. Cells, 11.","DOI":"10.3390\/cells11213439"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/nar\/gky947","article-title":"DNMT3L Facilitates DNA Methylation Partly by Maintaining DNMT3A Stability in Mouse Embryonic Stem Cells","volume":"47","author":"Veland","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bronner, C., Alhosin, M., Hamiche, A., and Mousli, M. (2019). Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns. Genes, 10.","DOI":"10.3390\/genes10010065"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/cbic.201000195","article-title":"Structure and Function of Mammalian DNA Methyltransferases","volume":"12","author":"Jurkowska","year":"2011","journal-title":"ChemBioChem"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.biochi.2020.07.004","article-title":"De Novo Methyltransferases: Potential Players in Diseases and New Directions for Targeted Therapy","volume":"176","author":"Saravanaraman","year":"2020","journal-title":"Biochimie"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/j.febslet.2009.04.012","article-title":"CpG Islands\u2014\u2018A Rough Guide\u2019","volume":"583","author":"Illingworth","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8349","DOI":"10.1093\/nar\/gkaa556","article-title":"Transcription of Intragenic CpG Islands Influences Spatiotemporal Host Gene Pre-MRNA Processing","volume":"48","author":"Amante","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"832348","DOI":"10.3389\/fcell.2022.832348","article-title":"Intragenic CpG Islands and Their Impact on Gene Regulation","volume":"10","author":"Cain","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/21541264.2017.1373209","article-title":"Orphan CpG Islands as Alternative Promoters","volume":"9","author":"Sarda","year":"2018","journal-title":"Transcription"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrg.2017.33","article-title":"TET-Mediated Active DNA Demethylation: Mechanism, Function and Beyond","volume":"18","author":"Wu","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/nature09303","article-title":"Role of Tet Proteins in 5mC to 5hmC Conversion, ES-Cell Self-Renewal and Inner Cell Mass Specification","volume":"466","author":"Ito","year":"2010","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1126\/science.1210597","article-title":"Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine","volume":"333","author":"Ito","year":"2011","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"35334","DOI":"10.1074\/jbc.C111.284620","article-title":"Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine","volume":"286","author":"Maiti","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1042\/BST20180606","article-title":"TET Enzymes, DNA Demethylation and Pluripotency","volume":"47","author":"Ross","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/nsmb.2372","article-title":"5-HmC in the Brain Is Abundant in Synaptic Genes and Shows Differences at the Exon-Intron Boundary","volume":"19","author":"Khare","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.pharmthera.2018.11.001","article-title":"The Role of DNA Methylation in Epigenetics of Aging","volume":"195","author":"Unnikrishnan","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1042\/EBC20190037","article-title":"The DNA Methylation Landscape in Cancer","volume":"63","author":"Skvortsova","year":"2019","journal-title":"Essays Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.3389\/fgene.2019.01150","article-title":"DNA Methylation Cancer Biomarkers: Translation to the Clinic","volume":"10","author":"Locke","year":"2019","journal-title":"Front. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-3-319-53889-1_12","article-title":"DNA Methylation in Schizophrenia","volume":"Volume 978","year":"2017","journal-title":"Neuroepigenomics in Aging and Disease"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-3-319-53889-1_10","article-title":"DNA Methylation in Major Depressive Disorder","volume":"Volume 978","year":"2017","journal-title":"Neuroepigenomics in Aging and Disease"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.neurobiolaging.2008.12.005","article-title":"Epigenetic Changes in Alzheimer\u2019s Disease: Decrements in DNA Methylation","volume":"31","author":"Mastroeni","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/jnc.13646","article-title":"DNA Methylation in Parkinson\u2019s Disease","volume":"139","author":"Kaut","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"504","DOI":"10.2174\/1871527318666190809162631","article-title":"Aberrant DNA Methylation Pattern May Enhance Susceptibility to Migraine: A Novel Perspective","volume":"18","author":"Goel","year":"2019","journal-title":"CNSNDDT"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6495","DOI":"10.1002\/jcp.26497","article-title":"Histone Methylation and Acetylation in Macrophages as a Mechanism for Regulation of Inflammatory Responses","volume":"233","author":"Daskalaki","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1756-8935-3-18","article-title":"Lessons from Genome-Wide Studies: An Integrated Definition of the Coactivator Function of Histone Acetyl Transferases","volume":"3","author":"Anamika","year":"2010","journal-title":"Epigenetics Chromatin"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/bj20021321","article-title":"Histone Deacetylases (HDACs): Characterization of the Classical HDAC Family","volume":"370","author":"Caron","year":"2003","journal-title":"Biochem. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cell.2009.06.049","article-title":"Genome-Wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes","volume":"138","author":"Wang","year":"2009","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1158\/1541-7786.MCR-07-0324","article-title":"Histone Deacetylase Inhibitors: Overview and Perspectives","volume":"5","author":"Dokmanovic","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1080\/15592294.2020.1827723","article-title":"Recent Insights into Histone Acetyltransferase-1: Biological Function and Involvement in Pathogenesis","volume":"16","author":"Poziello","year":"2021","journal-title":"Epigenetics"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"a026831","DOI":"10.1101\/cshperspect.a026831","article-title":"HDACs and HDAC Inhibitors in Cancer Development and Therapy","volume":"6","author":"Li","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"576946","DOI":"10.3389\/fcell.2020.576946","article-title":"The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy","volume":"8","author":"Li","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3390\/pathophysiology29030038","article-title":"Critical Functions of Histone Deacetylases (HDACs) in Modulating Inflammation Associated with Cardiovascular Diseases","volume":"29","author":"Kulthinee","year":"2022","journal-title":"Pathophysiology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nrg.2017.57","article-title":"The Interplay of Epigenetic Marks during Stem Cell Differentiation and Development","volume":"18","author":"Atlasi","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF02686117","article-title":"Distribution of Histone Deacetylases 1\u201311 in the Rat Brain","volume":"31","author":"Broide","year":"2007","journal-title":"J. Mol. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/ijnp\/pyaa017","article-title":"Postnatal Ethanol Exposure Activates HDAC-Mediated Histone Deacetylation, Impairs Synaptic Plasticity Gene Expression and Behavior in Mice","volume":"23","author":"Shivakumar","year":"2020","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"35444","DOI":"10.1074\/jbc.M112.394544","article-title":"Histone Deacetylase-1 (HDAC1) Is a Molecular Switch between Neuronal Survival and Death","volume":"287","author":"Bardai","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"158","DOI":"10.2174\/1570159X19666210609160017","article-title":"Understanding the Role of Histone Deacetylase and Their Inhibitors InNeurodegenerative Disorders: Current Targets and Future Perspective","volume":"20","author":"Kumar","year":"2022","journal-title":"CN"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1101\/gad.1563807","article-title":"Histone Deacetylases 1 and 2 Redundantly Regulate Cardiac Morphogenesis, Growth, and Contractility","volume":"21","author":"Montgomery","year":"2007","journal-title":"Genes Dev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e12447","DOI":"10.1111\/cpr.12447","article-title":"Pharmacological or Transcriptional Inhibition of Both HDAC1 and 2 Leads to Cell Cycle Blockage and Apoptosis via P21 Waf1\/Cip1 and P19 INK4d Upregulation in Hepatocellular Carcinoma","volume":"51","author":"Zhou","year":"2018","journal-title":"Cell Prolif."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.immuni.2018.02.016","article-title":"Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner","volume":"48","author":"Datta","year":"2018","journal-title":"Immunity"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1038\/s41467-019-11409-0","article-title":"Class IIa HDACs Regulate Learning and Memory through Dynamic Experience-Dependent Repression of Transcription","volume":"10","author":"Zhu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.cell.2012.09.037","article-title":"HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory","volume":"151","author":"Sando","year":"2012","journal-title":"Cell"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Da\u015bko, M., de Pascual-Teresa, B., Ort\u00edn, I., and Ramos, A. (2022). HDAC Inhibitors: Innovative Strategies for Their Design and Applications. Molecules, 27.","DOI":"10.3390\/molecules27030715"},{"key":"ref_111","first-page":"64","article-title":"HDAC Inhibitors with Potential to Overcome Drug Resistance in Castration-Resistant Prostate Cancer","volume":"5","author":"Biersack","year":"2022","journal-title":"CDR"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1093\/jnen\/nly073","article-title":"Histone Deacetylase Inhibitors: A Therapeutic Key in Neurological Disorders?","volume":"77","author":"Jaworska","year":"2018","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1016\/j.jpain.2022.05.007","article-title":"Histone Deacetylase Inhibitors Counteract CGRP Signaling and Pronociceptive Sensitization in a Rat Model of Medication Overuse Headache","volume":"23","author":"Urru","year":"2022","journal-title":"J. Pain"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mrrev.2017.09.003","article-title":"Histone Methylation and the DNA Damage Response","volume":"780","author":"Gong","year":"2019","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Basavarajappa, B.S., and Subbanna, S. (2021). Histone Methylation Regulation in Neurodegenerative Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094654"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/bcpt.12878","article-title":"Understanding Epigenetic Effects of Endocrine Disrupting Chemicals: From Mechanisms to Novel Test Methods","volume":"122","year":"2018","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s40610-016-0030-x","article-title":"Prenatal Maternal Stress and Epigenetics: Review of the Human Research","volume":"2","author":"Laplante","year":"2016","journal-title":"Curr. Mol. Biol. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1001\/jama.1992.03480090092034","article-title":"The Concepts of Stress and Stress System Disorders. Overview of Physical and Behavioral Homeostasis","volume":"267","author":"Chrousos","year":"1992","journal-title":"JAMA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00281-020-00827-8","article-title":"Control of Immunity by Glucocorticoids in Health and Disease","volume":"42","author":"Shimba","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.neubiorev.2016.06.003","article-title":"Life Stress, Glucocorticoid Signaling, and the Aging Epigenome: Implications for Aging-Related Diseases","volume":"74","author":"Gassen","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Mourtzi, N., Sertedaki, A., and Charmandari, E. (2021). Glucocorticoid Signaling and Epigenetic Alterations in Stress-Related Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115964"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Gazerani, P. (2020). Migraine and Diet. Nutrients, 12.","DOI":"10.3390\/nu12061658"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/s41582-022-00714-w","article-title":"Gene\u2013Environment Interactions in Alzheimer Disease: The Emerging Role of Epigenetics","volume":"18","author":"Migliore","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"871820","DOI":"10.3389\/fgene.2022.871820","article-title":"Association Studies of Environmental Exposures, DNA Methylation and Children\u2019s Cognitive, Behavioral, and Mental Health Problems","volume":"13","author":"Guo","year":"2022","journal-title":"Front. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"106321","DOI":"10.1016\/j.envint.2020.106321","article-title":"Prenatal Methylmercury Exposure and DNA Methylation in Seven-Year-Old Children in the Seychelles Child Development Study","volume":"147","author":"Gliga","year":"2021","journal-title":"Environ. Int."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s40572-018-0184-1","article-title":"Long-Term Health Effects and Underlying Biological Mechanisms of Developmental Exposure to Arsenic","volume":"5","author":"Smeester","year":"2018","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s40572-022-00382-4","article-title":"Metals Exposures and DNA Methylation: Current Evidence and Future Directions","volume":"9","author":"Elkin","year":"2022","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"110629","DOI":"10.1016\/j.exger.2019.06.002","article-title":"Early Impairment of Epigenetic Pattern in Neurodegeneration: Additional Mechanisms behind Pyrethroid Toxicity","volume":"124","author":"Bordoni","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1080\/15592294.2019.1638701","article-title":"DNA Hypermethylation in Disease: Mechanisms and Clinical Relevance","volume":"14","author":"Ehrlich","year":"2019","journal-title":"Epigenetics"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gendis.2018.01.002","article-title":"DNA Methylation in Human Diseases","volume":"5","author":"Jin","year":"2018","journal-title":"Genes Dis."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/onc.2017.374","article-title":"DNA Methylation Aberrancies Delineate Clinically Distinct Subsets of Colorectal Cancer and Provide Novel Targets for Epigenetic Therapies","volume":"37","author":"Weisenberger","year":"2018","journal-title":"Oncogene"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41571-018-0004-4","article-title":"Analysis of DNA Methylation in Cancer: Location Revisited","volume":"15","author":"Koch","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1053\/j.gastro.2017.10.007","article-title":"DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells from Pediatric Patients with Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate with Outcome","volume":"154","author":"Howell","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jpsychires.2021.06.013","article-title":"DNA Methylation Signature as a Biomarker of Major Neuropsychiatric Disorders","volume":"141","author":"Maloum","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0304-3959(03)00293-8","article-title":"Factors Associated with the Onset and Remission of Chronic Daily Headache in a Population-Based Study","volume":"106","author":"Scher","year":"2003","journal-title":"Pain"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"705276","DOI":"10.3389\/fpain.2021.705276","article-title":"Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives","volume":"2","author":"Mungoven","year":"2021","journal-title":"Front. Pain Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nrneurol.2012.13","article-title":"Chronic Migraine\u2014Classification, Characteristics and Treatment","volume":"8","author":"Diener","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1468-2982.2009.01941.x","article-title":"Global Prevalence of Chronic Migraine: A Systematic Review","volume":"30","author":"Natoli","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/nn.2900","article-title":"Neuronal Activity Modifies the DNA Methylation Landscape in the Adult Brain","volume":"14","author":"Guo","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA Methylation-Based Biomarkers and the Epigenetic Clock Theory of Ageing","volume":"19","author":"Horvath","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.18632\/aging.100859","article-title":"Increased Epigenetic Age and Granulocyte Counts in the Blood of Parkinson\u2019s Disease Patients","volume":"7","author":"Horvath","year":"2015","journal-title":"Aging"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.18632\/aging.100864","article-title":"Epigenetic Age of the Pre-Frontal Cortex Is Associated with Neuritic Plaques, Amyloid Load, and Alzheimer\u2019s Disease Related Cognitive Functioning","volume":"7","author":"Levine","year":"2015","journal-title":"Aging"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"174480691987181","DOI":"10.1177\/1744806919871819","article-title":"Epigenetic Aging Is Associated with Clinical and Experimental Pain in Community-Dwelling Older Adults","volume":"15","author":"Sinha","year":"2019","journal-title":"Mol. Pain"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/B978-0-12-801311-3.00003-2","article-title":"The Epigenetic Landscape of Alcoholism","volume":"Volume 115","author":"Krishnan","year":"2014","journal-title":"International Review of Neurobiology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tins.2015.02.001","article-title":"Epigenetic Mechanisms of Chronic Pain","volume":"38","author":"Descalzi","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.tcb.2008.04.003","article-title":"HDAC6: A Key Regulator of Cytoskeleton, Cell Migration and Cell\u2013Cell Interactions","volume":"18","author":"Cabrero","year":"2008","journal-title":"Trends Cell Biol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/nm.2396","article-title":"HDAC6 Inhibitors Reverse Axonal Loss in a Mouse Model of Mutant HSPB1\u2013Induced Charcot-Marie-Tooth Disease","volume":"17","author":"Krishnan","year":"2011","journal-title":"Nat. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1128\/MMBR.00043-14","article-title":"JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships","volume":"80","author":"Zeke","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1073\/pnas.85.5.1487","article-title":"A Gene Activated by Growth Factors Is Related to the Oncogene V-Jun","volume":"85","author":"Ryder","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0165-0173(98)00018-6","article-title":"Inducible and Constitutive Transcription Factors in the Mammalian Nervous System: Control of Gene Expression by Jun, Fos and Krox, and CREB\/ATF Proteins","volume":"28","author":"Herdegen","year":"1998","journal-title":"Brain Res. Rev."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0301-0082(99)00042-8","article-title":"JNK and P38 Stresskinases\u2014Degenerative Effectors of Signal-Transduction-Cascades in the Nervous System","volume":"61","author":"Mielke","year":"2000","journal-title":"Prog. Neurobiol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Wang, J., Yun, F., Sui, J., Liang, W., Shen, D., and Zhang, Q. (2022). HAT- and HDAC-Targeted Protein Acetylation in the Occurrence and Treatment of Epilepsy. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010088"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/164_2018_201","article-title":"Role of CGRP in Migraine","volume":"Volume 255","author":"Brain","year":"2019","journal-title":"Calcitonin Gene-Related Peptide (CGRP) Mechanisms"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1111\/j.1526-4610.2008.01215.x","article-title":"Inhibition of Calcitonin Gene-Related Peptide Function: A Promising Strategy for Treating Migraine","volume":"48","author":"Durham","year":"2008","journal-title":"Headache J. Head Face Pain"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1126\/science.6089345","article-title":"Alternative RNA Processing: Determining Neuronal Phenotype","volume":"225","author":"Rosenfeld","year":"1984","journal-title":"Science"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.4161\/epi.26645","article-title":"DNA Methylation Pattern of CALCA in Preterm Neonates with Bacterial Sepsis as a Putative Epigenetic Biomarker","volume":"8","author":"Tendl","year":"2013","journal-title":"Epigenetics"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4103\/0972-2327.182302","article-title":"Understanding Migraine: Potential Role of Neurogenic Inflammation","volume":"19","author":"Malhotra","year":"2016","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1177\/0333102417736900","article-title":"Recognizing the Role of CGRP and CGRP Receptors in Migraine and Its Treatment","volume":"39","author":"Edvinsson","year":"2019","journal-title":"Cephalalgia"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1517\/14728222.11.9.1179","article-title":"Novel Migraine Therapy with Calcitonin Gene-Regulated Peptide Receptor Antagonists","volume":"11","author":"Edvinsson","year":"2007","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/bcp.12686","article-title":"CGRP as a Neuropeptide in Migraine: Lessons from Mice: CGRP as a Neuropeptide in Migraine","volume":"80","author":"Russo","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/ana.410280213","article-title":"Vasoactive Peptide Release in the Extracerebral Circulation of Humans during Migraine Headache","volume":"28","author":"Goadsby","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1212\/WNL.0b013e3182a6cb72","article-title":"Interictal Increase of CGRP Levels in Peripheral Blood as a Biomarker for Chronic Migraine","volume":"81","author":"Larrosa","year":"2013","journal-title":"Neurology"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1007\/s12031-020-01493-z","article-title":"Expression of the CGRP Family of Neuropeptides and Their Receptors in the Trigeminal Ganglion","volume":"70","author":"Edvinsson","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-1-4614-2364-5_2","article-title":"RAMPs and CGRP Receptors","volume":"Volume 744","author":"Spielman","year":"2012","journal-title":"RAMPs"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.tips.2018.11.005","article-title":"New Insights into the Regulation of CGRP-Family Receptors","volume":"40","author":"Gingell","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.jpain.2009.03.018","article-title":"Genetic Enhancement of Calcitonin Gene-Related Peptide-Induced Central Sensitization to Mechanical Stimuli in Mice","volume":"10","author":"Hammond","year":"2009","journal-title":"J. Pain"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.neuropharm.2009.07.009","article-title":"Induction of Multiple Photophobic Behaviors in a Transgenic Mouse Sensitized to CGRP","volume":"58","author":"Recober","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_168","first-page":"607","article-title":"Review of the Endocannabinoid System","volume":"6","author":"Lu","year":"2021","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Meccariello, R., Santoro, A., D\u2019Angelo, S., Morrone, R., Fasano, S., Viggiano, A., and Pierantoni, R. (2020). The Epigenetics of the Endocannabinoid System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031113"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.neuropharm.2016.10.008","article-title":"Chronic Stress Leads to Epigenetic Dysregulation in the Neuropeptide-Y and Cannabinoid CB1 Receptor Genes in the Mouse Cingulate Cortex","volume":"113","author":"Lomazzo","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1053\/j.gastro.2016.04.015","article-title":"The Role of the Endocannabinoid System in the Brain\u2013Gut Axis","volume":"151","author":"Sharkey","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"105237","DOI":"10.1016\/j.phrs.2020.105237","article-title":"Epigenetics and the Endocannabinoid System Signaling: An Intricate Interplay Modulating Neurodevelopment","volume":"162","author":"Gomes","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"D\u2019Addario, C., Di Francesco, A., Arosio, B., Gussago, C., Dell\u2019Osso, B., Bari, M., Galimberti, D., Scarpini, E., Altamura, A.C., and Mari, D. (2012). Epigenetic Regulation of Fatty Acid Amide Hydrolase in Alzheimer Disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039186"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"14869","DOI":"10.1523\/JNEUROSCI.0943-13.2013","article-title":"Endocannabinoids in the Brainstem Modulate Dural Trigeminovascular Nociceptive Traffic via CB1 and \u201cTriptan\u201d Receptors: Implications in Migraine","volume":"33","author":"Akerman","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/head.12570","article-title":"Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It\u2019s Been\u2026","volume":"55","author":"Baron","year":"2015","journal-title":"Headache J. Head Face Pain"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1097\/WCO.0000000000000688","article-title":"The Endocannabinoid System in Migraine: From Bench to Pharmacy and Back","volume":"32","author":"Tassorelli","year":"2019","journal-title":"Curr. Opin. Neurol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41582-019-0284-z","article-title":"Cannabinoids and the Expanded Endocannabinoid System in Neurological Disorders","volume":"16","author":"Cristino","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000331474","article-title":"Regulation of Opioid and Cannabinoid Receptor Genes in Human Neuroblastoma and T Cells by the Epigenetic Modifiers Trichostatin A and 5-Aza-2\u2032-Deoxycytidine","volume":"19","author":"Martella","year":"2012","journal-title":"Neuroimmunomodulation"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1111\/febs.12125","article-title":"Epigenetic Mechanisms and Endocannabinoid Signalling","volume":"280","author":"Pucci","year":"2013","journal-title":"FEBS J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/ijc.10899","article-title":"Cannabinoids Inhibit Gap Junctional Intercellular Communication and Activate ERK in a Rat Liver Epithelial Cell Line","volume":"104","author":"Upham","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/jnc.13006","article-title":"CB1-Receptor Knockout Neonatal Mice Are Protected against Ethanol-Induced Impairments of DNMT1, DNMT3A, and DNA Methylation","volume":"132","author":"Nagre","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.biopsych.2012.04.026","article-title":"Proenkephalin Mediates the Enduring Effects of Adolescent Cannabis Exposure Associated with Adult Opiate Vulnerability","volume":"72","author":"Tomasiewicz","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1503\/jpn.170082","article-title":"Adolescent THC Exposure in Female Rats Leads to Cognitive Deficits through a Mechanism Involving Chromatin Modifications in the Prefrontal Cortex","volume":"43","author":"Prini","year":"2018","journal-title":"Jpn"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41398-017-0087-1","article-title":"Gene Variants and Educational Attainment in Cannabis Use: Mediating Role of DNA Methylation","volume":"8","author":"Gerra","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/j.1526-4610.2009.01570.x","article-title":"MTHFR 677C>T and ACE D\/I Polymorphisms in Migraine: A Systematic Review and Meta-Analysis","volume":"50","author":"Rist","year":"2010","journal-title":"Headache J. Head Face Pain"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41588-021-00990-0","article-title":"Genome-Wide Analysis of 102,084 Migraine Cases Identifies 123 Risk Loci and Subtype-Specific Risk Alleles","volume":"54","author":"Hautakangas","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_187","first-page":"e11725","article-title":"Advances in Epigenetic Cancer Therapeutics","volume":"12","author":"Hillyar","year":"2020","journal-title":"Cureus"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nrg3198","article-title":"MicroRNA Profiling: Approaches and Considerations","volume":"13","author":"Pritchard","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S1474-4422(17)30435-0","article-title":"The Pathophysiology of Migraine: Implications for Clinical Management","volume":"17","author":"Charles","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1007\/s12031-020-01788-1","article-title":"A Comprehensive Review on the Role of Genetic Factors in the Pathogenesis of Migraine","volume":"71","author":"Ebahimzadeh","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1002\/jcp.27486","article-title":"An Overview of MicroRNAs: Biology, Functions, Therapeutics, and Analysis Methods","volume":"234","author":"Saliminejad","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/bit.28029","article-title":"Biogenesis and Mechanisms of MicroRNA-mediated Gene Regulation","volume":"119","author":"Rani","year":"2022","journal-title":"Biotechnol. Bioeng."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/cbic.201402449","article-title":"MiRNA and Methylation: A Multifaceted Liaison","volume":"16","author":"Chhabra","year":"2015","journal-title":"ChemBioChem"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1007\/s00204-016-1815-7","article-title":"MicroRNA Epigenetic Signatures in Human Disease","volume":"90","author":"Kunej","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.molcel.2021.11.026","article-title":"Life of RISC: Formation, Action, and Degradation of RNA-Induced Silencing Complex","volume":"82","author":"Iwakawa","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41418-022-00948-7","article-title":"Specific Expression and Functions of Circular RNAs","volume":"29","author":"Misir","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.7150\/thno.42174","article-title":"Circular RNA-Protein Interactions: Functions, Mechanisms, and Identification","volume":"10","author":"Huang","year":"2020","journal-title":"Theranostics"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41576-019-0158-7","article-title":"The Biogenesis, Biology and Characterization of Circular RNAs","volume":"20","author":"Kristensen","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12943-020-01286-3","article-title":"Circular RNA: Metabolism, Functions and Interactions with Proteins","volume":"19","author":"Zhou","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_200","first-page":"67","article-title":"Circular RNAs Act as MiRNA Sponges","volume":"Volume 1087","author":"Xiao","year":"2018","journal-title":"Circular RNAs"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molcel.2014.08.019","article-title":"CircRNA Biogenesis Competes with Pre-MRNA Splicing","volume":"56","author":"Meyer","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Das, A., Sinha, T., Shyamal, S., and Panda, A.C. (2021). Emerging Role of Circular RNA\u2013Protein Interactions. ncRNA, 7.","DOI":"10.3390\/ncrna7030048"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1007\/s12094-020-02371-1","article-title":"The New Function of CircRNA: Translation","volume":"22","author":"Shi","year":"2020","journal-title":"Clin. Transl. Oncol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/ajmg.b.32599","article-title":"The Role of CLOCK Gene in Psychiatric Disorders: Evidence from Human and Animal Research","volume":"177","author":"Schuch","year":"2018","journal-title":"Am. J. Med. Genet."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1177\/0306312719866007","article-title":"Epigenetics, Ethics, Law and Society: A Multidisciplinary Review of Descriptive, Instrumental, Dialectical and Reflexive Analyses","volume":"49","author":"Dupras","year":"2019","journal-title":"Soc. Stud. Sci."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Cerde\u00f1a, J.P. (2022). Epigenetic Citizenship and Political Claims-Making: The Ethics of Molecularizing Structural Racism. BioSocieties.","DOI":"10.1057\/s41292-022-00286-4"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13148-022-01263-1","article-title":"Ethical Implications of Epigenetics in the Era of Personalized Medicine","volume":"14","author":"Berdasco","year":"2022","journal-title":"Clin. Epigenet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:40:05Z","timestamp":1760125205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":207,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24119127"],"URL":"https:\/\/doi.org\/10.3390\/ijms24119127","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]}}}