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Current Evidence on Potential Uses of MicroRNA Biomarkers for Migraine: From Diagnosis to Treatment

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Abstract

Migraine is a disabling and recurrent neurological disorder characterized by headache attacks that are often accompanied by sensory and motor disturbances. The value and importance of reliable biomarkers in migraine have been long recognized and a diverse range of biomarkers from biological samples to electrophysiological patterns and brain imaging has been proposed. There is still no consensus on specific biomarker(s) for migraine. Ideally, not a single but a battery of biomarkers would provide a multidisciplinary way to understand and treat migraine better. Translational research has witnessed an escalating number of studies on microRNAs (miRNAs) during the last decade. Identification of the first miRNA occurred in 1993, and currently more than 2000 human miRNAs have been recognized. miRNAs are a group of endogenous small non-coding molecules that play a key role in post-transcriptional gene processes and hence are involved in health and disease. miRNAs have already been found to be involved in the onset and progression of several human disorders including chronic pain conditions; however, there have been far fewer studies in migraine and other headaches. Current evidence does suggest that miRNAs play a role in migraine and its relief and hence these molecules are proposed as potential migraine biomarkers. This review updates the current evidence for the role of miRNAs in migraine; including their potential as biomarkers, with a role in understanding of its pathogenesis, the population at risk, diagnosis, patient stratification, chronification risk factors, response to treatments, and miRNA-based therapeutic options. Limitations exist and further research is required to completely unwrap the potential of miRNAs in migraine research and practice.

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Reused with permission, copyright © 2018 Dai et al. [95], https://doi.org/10.3389/fnmol.2018.00080, The Creative Commons Attribution License (CCBY)

Fig. 2

Reused with permission, copyright © 2018 Dai et al. [95], The Creative Commons Attribution License (CCBY), https://doi.org/10.3389/fnmol.2018.00080

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References

  1. Steiner TJ, Stovner LJ, Vos T, Jensen R, Katsarava Z. Migraine is first cause of disability in under 50 s: will health politicians now take notice? J Headache Pain. 2018;19:17. https://doi.org/10.1186/s10194-018-0846-2.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lanteri-Minet M. Economic burden and costs of chronic migraine. Curr Pain Headache Rep. 2013;18(1):385. https://doi.org/10.1007/s11916-013-0385-0.

    Article  Google Scholar 

  3. Straube A, Andreou AP. Primary headaches during lifespan. J Headache Pain. 2019;20:71. https://doi.org/10.1186/s10194-019-1025-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and CrossMark pathophysiology of migraine. Lancet Neurol. 2017;16(1):76–87. https://doi.org/10.1016/S1474-4422(16)30293-9.

    Article  CAS  PubMed  Google Scholar 

  5. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.

  6. Dodick DW. Migraine. Lancet. 2018;391(10127):1315–30. https://doi.org/10.1016/S0140-6736(18)30478-1.

    Article  PubMed  Google Scholar 

  7. Russo A, Silvestro M, Tessitore A, Tedeschi G. Recent insights in migraine with aura: a narrative review of advanced neuroimaging. Headache. 2019;59(4):637–49. https://doi.org/10.1111/head.13512.

    Article  PubMed  Google Scholar 

  8. Hadjikhani N, Vincent M. Neuroimaging clues of migraine aura. J Headache Pain. 2019;20:32. https://doi.org/10.1186/s10194-019-0983-2.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Manzoni GC, Torelli P. Migraine with and without aura: a single entity? Neurol Sci. 2008;29:S40–3. https://doi.org/10.1007/s10072-008-0884-7.

    Article  PubMed  Google Scholar 

  10. Russell MB, Ulrich V, Gervil M, Olesen J. Migraine without aura and migraine with aura are distinct disorders. A population-based twin survey. Headache. 2002;42(5):332–6. https://doi.org/10.1046/j.1526-4610.2002.02102.x.

    Article  PubMed  Google Scholar 

  11. Ligthart L, Boomsma DI, Martin NG, Stubbe JH, Nyholt DR. Migraine with aura and migraine without aura are not distinct entities: further evidence from a large Dutch population study. Twin Res Hum Genet. 2006;9(1):54–63. https://doi.org/10.1375/183242706776403019.

    Article  PubMed  Google Scholar 

  12. Viana M, Linde M, Sances G, Ghiotto N, Guaschino E, Allena M, et al. Migraine aura symptoms: duration, succession and temporal relationship to headache. Cephalalgia. 2016;36(5):413–21. https://doi.org/10.1177/0333102415593089.

    Article  PubMed  Google Scholar 

  13. Viana M, Tronvik EA, Do TP, Zecca C, Hougaard A. Clinical features of visual migraine aura: a systematic review. J Headache Pain. 2019;20:64. https://doi.org/10.1186/s10194-019-1008-x.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018;17(2):174–82. https://doi.org/10.1016/S1474-4422(17)30435-0.

    Article  CAS  PubMed  Google Scholar 

  15. Sutherland HG, Albury CL, Griffiths LR. Advances in genetics of migraine. J Headache Pain. 2019;20:72. https://doi.org/10.1186/s10194-019-1017-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kondratieva N, Azimova J, Skorobogatykh K, Sergeev A, Naumova E, Kokaeva Z, et al. Biomarkers of migraine: part 1 - genetic markers. J Neurol Sci. 2016;369:63–76. https://doi.org/10.1016/j.jns.2016.08.008.

    Article  CAS  PubMed  Google Scholar 

  17. Gazerani P. Current evidence on the role of epigenetic mechanisms in migraine: the way forward to precision medicine. OBM Genet. 2018;2(4):040. https://doi.org/10.21926/obm.genet.1804040.

  18. Eising E, Datson NA, van den Maagdenberg AMJM, Ferrari MD. Epigenetic mechanisms in migraine: a promising avenue? BMC Med. 2013;11:26. https://doi.org/10.1186/1741-7015-11-26.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Terlizzi R, Bacalini MG, Pirazzini C, Giannini G, Pierangeli G, Garagnani P, et al. Epigenetic DNA methylation changes in episodic and chronic migraine. Neurol Sci. 2018;39:S67–8. https://doi.org/10.1007/s10072-018-3348-8.

    Article  Google Scholar 

  20. Lipton RB, Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache. 2015;55 Suppl 2:103–22 (quiz 23–6). https://doi.org/10.1111/head.12505_2.

  21. Katsarava Z, Buse DC, Manack AN, Lipton RB. Defining the differences between episodic migraine and chronic migraine. Curr Pain Headache Rep. 2012;16(1):86–92. https://doi.org/10.1007/s11916-011-0233-z.

    Article  PubMed  Google Scholar 

  22. Zhang LM, Dong Z, Yu SY. Migraine in the era of precision medicine. Ann Transl Med. 2016;4(6):105. https://doi.org/10.21037/atm.2016.03.13.

  23. Antonaci F, Ghiotto N, Wu SZ, Pucci E, Costa A. Recent advances in migraine therapy. Springerplus. 2016;5:637. https://doi.org/10.1186/s40064-016-2211-8.

    Article  CAS  PubMed  Google Scholar 

  24. Gooriah R, Nimeri R, Ahmed F. Evidence-based treatments for adults with migraine. Pain Res Treat. 2015;2015:629382. https://doi.org/10.1155/2015/629382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Scuteri D, Adornetto A, Rombola L, Naturale MD, Morrone LA, Bagetta G, et al. New trends in migraine pharmacology: targeting calcitonin gene-related peptide (CGRP) with monoclonal antibodies. Front Pharmacol. 2019;10:363. https://doi.org/10.3389/fphar.2019.00363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tringali G, Navarra P. Anti-CGRP and anti-CGRP receptor monoclonal antibodies as antimigraine agents. Potential differences in safety profile postulated on a pathophysiological basis. Peptides. 2019;116:16–21. https://doi.org/10.1016/j.peptides.2019.04.012.

  27. Tepper SJ. History and review of anti-calcitonin gene-related peptide (CGRP) therapies: from translational research to treatment. Headache. 2018;58:238–75. https://doi.org/10.1111/head.13379.

    Article  PubMed  Google Scholar 

  28. Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. N Engl J Med. 2019;381(2):142–9. https://doi.org/10.1056/NEJMoa1811090.

    Article  PubMed  Google Scholar 

  29. Moreno-Ajona D, Chan C, Villar-Martinez MD, Goadsby PJ. Targeting CGRP and 5-HT1F receptors for the acute therapy of migraine: a literature review. Headache. 2019;59(Suppl 2):3–19. https://doi.org/10.1111/head.13582.

    Article  PubMed  Google Scholar 

  30. Negro A, Martelletti P. Gepants for the treatment of migraine. Expert Opin Investig Drugs. 2019;28(6):555–67. https://doi.org/10.1080/13543784.2019.1618830.

    Article  CAS  PubMed  Google Scholar 

  31. Gallelli L, Cione E, Caroleo MC, Carotenuto M, Lagana P, Siniscalchi A, et al. microRNAs to monitor pain-migraine and drug treatment. Microrna. 2017;6(3):152–6. https://doi.org/10.2174/2211536606666170913152821.

    Article  CAS  PubMed  Google Scholar 

  32. Borsook D, Becerra L, Hargreaves R. Biomarkers for chronic pain and analgesia. Part 1: the need, reality, challenges, and solutions. Discov Med. 2011;11(58):197–207.

  33. Borsook D, Becerra L, Hargreaves R. Biomarkers for chronic pain and analgesia. Part 2: how, where, and what to look for using functional imaging. Discov Med. 2011;11(58):209–19.

  34. Durham P, Papapetropoulos S. Biomarkers associated with migraine and their potential role in migraine management. Headache. 2013;53(8):1262–77. https://doi.org/10.1111/head.12174.

    Article  PubMed  Google Scholar 

  35. Loder E, Graham JR. From subjective to objective: biomarkers in migraine. Headache. 2006;46(7):1045. https://doi.org/10.1111/j.1526-4610.2006.00497.x.

    Article  Google Scholar 

  36. Kowalska M, Prendecki M, Kozubski W, Lianeri M, Dorszewska J. Molecular factors in migraine. Oncotarget. 2016;7(31):50708–18. https://doi.org/10.18632/oncotarget.9367.

  37. Kowalska M, Kapelusiak-Pielok M, Grzelak T, Wypasek E, Kozubski W, Dorszewska J. The new *G29A and G1222A of HCRTR1, 5-HTTLPR of SLC6A4 Polymorphisms and hypocretin-1, serotonin concentrations in migraine patients. Front Mol Neurosci. 2018;11:191. https://doi.org/10.3389/fnmol.2018.00191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Loder E, Rizzoli P. Biomarkers in migraine: their promise, problems, and practical applications. Headache. 2006;46(7):1046–58. https://doi.org/10.1111/j.1526-4610.2006.00498.x.

    Article  PubMed  Google Scholar 

  39. Loder E, Harrington MG, Cutrer M, Sandor P, De Vries B. Selected confirmed, probable, and exploratory migraine biomarkers. Headache. 2006;46(7):1108–27. https://doi.org/10.1111/j.1526-4610.2006.00525.x.

    Article  PubMed  Google Scholar 

  40. Califf RM. Biomarker definitions and their applications. Exp Biol Med. 2018;243(3):213–21. https://doi.org/10.1177/1535370217750088.

    Article  CAS  Google Scholar 

  41. Neuroscience biomarkers and biosignatures: converging technologies, emerging partnerships, workshop summary. The National Academies Collection: reports funded by National Institutes of Health. Washington, DC: The National Academies Press; 2008.

  42. Belvís R, Pozo-Rosich P, Pascual J. New insights into diagnostic biomarkers of migraine: biological, genetic and radiological. Int J Neuro Disord Interv. 2015;1:105. https://doi.org/10.15344/ijndi/2015/105.

  43. Drucker E, Krapfenbauer K. Pitfalls and limitations in translation from biomarker discovery to clinical utility in predictive and personalised medicine. EPMA J. 2013;4(1):7. https://doi.org/10.1186/1878-5085-4-7.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mayeux R. Biomarkers: potential uses and limitations. NeuroRx. 2004;1(2):182–8. https://doi.org/10.1602/neurorx.1.2.182.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Casteleyn L, Dumez B, Van Damme K, Anwar WA. Ethics and data protection in human biomarker studies in environmental health. Int J Hyg Envir Heal. 2013;216(5):599–605. https://doi.org/10.1016/j.ijheh.2013.03.016.

    Article  Google Scholar 

  46. Coppola L, Cianflone A, Grimaldi AM, Incoronato M, Bevilacqua P, Messina F, et al. Biobanking in health care: evolution and future directions. J Transl Med. 2019;17:172. https://doi.org/10.1186/s12967-019-1922-3.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kuzhandai Velu V, Ramesh R, Srinivasan AR. Circulating MicroRNAs as biomarkers in health and disease. J Clin Diagn Res. 2012;6(10):1791–5. https://doi.org/10.7860/JCDR/2012/4901.2653.

    Article  CAS  PubMed  Google Scholar 

  48. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74. https://doi.org/10.1038/nrg3074.

    Article  CAS  PubMed  Google Scholar 

  49. Backes C, Meese E, Keller A. Specific miRNA disease biomarkers in blood, serum and plasma: challenges and prospects. Mol Diagn Ther. 2016;20(6):509–18. https://doi.org/10.1007/s40291-016-0221-4.

    Article  CAS  PubMed  Google Scholar 

  50. Trzybulska D, Vergadi E, Tsatsanis C. miRNA and other non-coding RNAs as promising diagnostic markers. EJIFCC. 2018;29(3):221–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Wei JW, Huang K, Yang C, Kang CS. Non-coding RNAs as regulators in epigenetics. Oncol Rep. 2017;37(1):3–9. https://doi.org/10.3892/or.2016.5236.

    Article  PubMed  Google Scholar 

  52. Camara MS, Martin Bujanda M, Mendioroz Iriarte M. Epigenetic changes in headache. Neurologia Epub. 2017. https://doi.org/10.1016/j.nrl.2017.10.010.

    Article  Google Scholar 

  53. Kreth S, Hubner M, Hinske LC. MicroRNAs as clinical biomarkers and therapeutic tools in perioperative medicine. Anesth Analg. 2018;126(2):670–81. https://doi.org/10.1213/Ane.0000000000002444.

    Article  CAS  PubMed  Google Scholar 

  54. Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, et al. The microRNAs of Caenorhabditis elegans. Gene Dev. 2003;17(8):991–1008. https://doi.org/10.1101/gad.1074403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. O’Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018;9:402. https://doi.org/10.3389/fendo.2018.00402.

    Article  Google Scholar 

  56. Coenen-Stass AML, Magen I, Brooks T, Ben-Dov IZ, Greensmith L, Hornstein E, et al. Evaluation of methodologies for microRNA biomarker detection by next generation sequencing. RNA Biol. 2018;15(8):1133–45. https://doi.org/10.1080/15476286.2018.1514236.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Li Y, Kowdley KV. MicroRNAs in common human diseases. Genom Proteom Bioinform. 2012;10(5):246–53. https://doi.org/10.1016/j.gpb.2012.07.005.

    Article  CAS  Google Scholar 

  58. Kandhro AH. MicroRNAs from diagnosis to therapy: future perspective. Transl Biomed. 2016. https://doi.org/10.2167/2172-0479.100089.

    Article  Google Scholar 

  59. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20. https://doi.org/10.1016/j.cell.2004.12.035.

    Article  CAS  PubMed  Google Scholar 

  60. Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1):D155–62. https://doi.org/10.1093/nar/gky1141.

    Article  CAS  PubMed  Google Scholar 

  61. Alles J, Fehlmann T, Fischer U, Backes C, Galata V, Minet M, et al. An estimate of the total number of true human miRNAs. Nucleic Acids Res. 2019;47(7):3353–64. https://doi.org/10.1093/nar/gkz097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33. https://doi.org/10.1016/j.cell.2009.01.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97. https://doi.org/10.1016/S0092-8674(04)00045-5.

    Article  CAS  PubMed  Google Scholar 

  64. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013;12(11):847–65. https://doi.org/10.1038/nrd4140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Osman A. MicroRNAs in health and disease—basic science and clinical applications. Clin Lab. 2012;58(5–6):393–402.

    CAS  PubMed  Google Scholar 

  66. Ardekani AM, Naeini MM. The role of microRNAs in human diseases. Avicenna J Med Biotechnol. 2010;2(4):161–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Tufekci KU, Oner MG, Meuwissen RL, Genc S. The role of microRNAs in human diseases. Methods Mol Biol. 2014;1107:33–50. https://doi.org/10.1007/978-1-62703-748-8_3.

    Article  CAS  PubMed  Google Scholar 

  68. Treiber T, Treiber N, Meister G. Author correction: regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol. 2018;19(12):808. https://doi.org/10.1038/s41580-018-0070-6.

    Article  CAS  PubMed  Google Scholar 

  69. Ma YH. The challenge of microRNA as a biomarker of epilepsy. Curr Neuropharmacol. 2018;16(1):37–42. https://doi.org/10.2174/1570159x15666170703102410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Swarbrick S, Wragg N, Ghosh S, Stolzing A. Systematic review of miRNA as biomarkers in Alzheimer’s disease. Mol Neurobiol. 2019;56(9):6156–67. https://doi.org/10.1007/s12035-019-1500-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhou SS, Jin JP, Wang JQ, Zhang ZG, Freedman JH, Zheng Y, et al. miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges. Acta Pharmacol Sin. 2018;39(7):1073–84. https://doi.org/10.1038/aps.2018.30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ojha R, Nandani R, Pandey RK, Mishra A, Prajapati VK. Emerging role of circulating microRNA in the diagnosis of human infectious diseases. J Cell Physiol. 2019;234(2):1030–43. https://doi.org/10.1002/jcp.27127.

    Article  CAS  PubMed  Google Scholar 

  73. Tana C, Giamberardino MA, Cipollone F. microRNA profiling in atherosclerosis, diabetes, and migraine. Ann Med. 2017;49(2):93–105. https://doi.org/10.1080/07853890.2016.1226515.

    Article  CAS  PubMed  Google Scholar 

  74. Slota JA, Booth SA. MicroRNAs in Neuroinflammation: implications in disease pathogenesis, biomarker discovery and therapeutic applications. Noncoding RNA. 2019;5(2):E35. https://doi.org/10.3390/ncrna5020035.

    Article  CAS  PubMed  Google Scholar 

  75. Gambari R, Fabbri E, Borgatti M, Lampronti I, Finotti A, Brognara E, et al. Targeting microRNAs involved in human diseases: a novel approach for modification of gene expression and drug development. Biochem Pharmacol. 2011;82(10):1416–29. https://doi.org/10.1016/j.bcp.2011.08.007.

    Article  CAS  PubMed  Google Scholar 

  76. Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet. 2019;10:478. https://doi.org/10.3389/fgene.2019.00478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lopez-Gonzalez MJ, Landry M, Favereaux A. MicroRNA and chronic pain: from mechanisms to therapeutic potential. Pharmacol Ther. 2017;180:1–15. https://doi.org/10.1016/j.pharmthera.2017.06.001.

    Article  CAS  PubMed  Google Scholar 

  78. Andersen HH, Duroux M, Gazerani P. MicroRNAs as modulators and biomarkers of inflammatory and neuropathic pain conditions. Neurobiol Dis. 2014;71:159–68. https://doi.org/10.1016/j.nbd.2014.08.003.

    Article  CAS  PubMed  Google Scholar 

  79. Dayer CF, Luthi F, Le Carre J, Vuistiner P, Terrier P, Benaim C, et al. Differences in the miRNA signatures of chronic musculoskeletal pain patients from neuropathic or nociceptive origins. PLoS One. 2019;14(7):e0219311. https://doi.org/10.1371/journal.pone.0219311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ramanathan S, Ajit SK. MicroRNA-based biomarkers in pain. Adv Pharmacol. 2016;75:35–62. https://doi.org/10.1016/bs.apha.2015.12.001.

    Article  CAS  PubMed  Google Scholar 

  81. McDonald MK, Ajit SK. MicroRNA biology and pain. Prog Mol Biol Transl Sci. 2015;131:215–49. https://doi.org/10.1016/bs.pmbts.2014.11.015.

    Article  PubMed  Google Scholar 

  82. Orlova IA, Alexander GM, Qureshi RA, Sacan A, Graziano A, Barrett JE, et al. MicroRNA modulation in complex regional pain syndrome. J Transl Med. 2011;9:195. https://doi.org/10.1186/1479-5876-9-195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhai Y, Zhu YY. MiR-30a relieves migraine by degrading CALCA. Eur Rev Med Pharmacol Sci. 2018;22(7):2022–8.

    CAS  PubMed  Google Scholar 

  84. Tafuri E, Santovito D, de Nardis V, Marcantonio P, Paganelli C, Affaitati G, et al. MicroRNA profiling in migraine without aura: pilot study. Ann Med. 2015;47(6):468–73. https://doi.org/10.3109/07853890.2015.1071871.

    Article  CAS  PubMed  Google Scholar 

  85. Cheng CY, Chen SP, Liao YC, Fuh JL, Wang YF, Wang SJ. Elevated circulating endothelial-specific microRNAs in migraine patients: a pilot study. Cephalalgia. 2018;38(9):1585–91. https://doi.org/10.1177/0333102417742375.

    Article  PubMed  Google Scholar 

  86. Andersen HH, Duroux M, Gazerani P. Serum microRNA signatures in migraineurs during attacks and in pain-free periods. Mol Neurobiol. 2016;53(3):1494–500. https://doi.org/10.1007/s12035-015-9106-5.

    Article  CAS  PubMed  Google Scholar 

  87. Sakai A, Suzuki H. microRNA and pain. Adv Exp Med Biol. 2015;888:17–39. https://doi.org/10.1007/978-3-319-22671-2_3.

    Article  CAS  PubMed  Google Scholar 

  88. Sakai A, Suzuki H. Emerging roles of microRNAs in chronic pain. Neurochem Int. 2014;77:58–67. https://doi.org/10.1016/j.neuint.2014.05.010.

    Article  CAS  PubMed  Google Scholar 

  89. Odell DW. Epigenetics of pain mediators. Curr Opin Anesthesiol. 2018;31(4):402–6. https://doi.org/10.1097/Aco.0000000000000613.

    Article  Google Scholar 

  90. Andersen HH, Gazerani P. MicroRNAs and pain. In: Ruberti F, editor. Mapping of nervous system diseases via MicroRNAs. Frontiers in neurotherapeutics series. Boca Raton: CRC; 2016. p. 181–202.

    Google Scholar 

  91. Kress M, Huttenhofer A, Landry M, Kuner R, Favereaux A, Greenberg D, et al. microRNAs in nociceptive circuits as predictors of future clinical applications. Front Mol Neurosci. 2013;6:33. https://doi.org/10.3389/fnmol.2013.00033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lutz BM, Bekker A, Tao YX. Noncoding RNAs new players in chronic pain. Anesthesiology. 2014;121(2):409–17. https://doi.org/10.1097/Aln.0000000000000265.

    Article  CAS  PubMed  Google Scholar 

  93. Qureshi RA, Tian Y, McDonald MK, Capasso KE, Douglas SR, Gao R, et al. Circulating microRNA signatures in rodent models of pain. Mol Neurobiol. 2016;53(5):3416–27. https://doi.org/10.1007/s12035-015-9281-4.

    Article  CAS  PubMed  Google Scholar 

  94. Guo JB, Zhu Y, Chen BL, Song G, Peng MS, Hu HY, et al. Network and pathway-based analysis of microRNA role in neuropathic pain in rat models. J Cell Mol Med. 2019;23(7):4534–44. https://doi.org/10.1111/jcmm.14357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Dai Z, Chu HC, Ma JH, Yan Y, Zhang XY, Liang YX. The regulatory mechanisms and therapeutic potential of microRNAs: from chronic pain to morphine tolerance. Front Mol Neurosci. 2018;11:80. https://doi.org/10.3389/fnmol.2018.00080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ramanathan S, Shenoda BB, Ajit SK. Overview of microRNA modulation in analgesic research. Curr Protoc Pharmacol. 2017;79:9.25.1–9.25.10. https://doi.org/10.1002/cpph.29.

  97. Toyama K, Kiyosawa N, Watanabe K, Ishizuka H. Identification of circulating miRNAs differentially regulated by opioid treatment. Int J Mol Sci. 2017;18(9):E1991. https://doi.org/10.3390/ijms18091991.

    Article  CAS  PubMed  Google Scholar 

  98. Kiyosawa N, Watanabe K, Toyama K, Ishizuka H. Circulating miRNA signature as a potential biomarker for the prediction of analgesic efficacy of hydromorphone. Int J Mol Sci. 2019;20(7):1665. https://doi.org/10.3390/ijms20071665.

    Article  CAS  PubMed Central  Google Scholar 

  99. Kynast KL, Russe OQ, Geisslinger G, Niederberger E. Novel findings in pain processing pathways: implications for miRNAs as future therapeutic targets. Expert Rev Neurother. 2013;13(5):515–25. https://doi.org/10.1586/Ern.13.34.

    Article  CAS  PubMed  Google Scholar 

  100. Niederberger E, Resch E, Parnham MJ, Geisslinger G. Drugging the pain epigenome. Nat Rev Neurol. 2017;13(7):434–47. https://doi.org/10.1038/nrneurol.2017.68.

    Article  CAS  PubMed  Google Scholar 

  101. Andersen HH, Duroux M, Gazerani P. MicroRNAs as modulators and biomarkers of inlammatory and neuropathic pain conditions. Neurobiol Dis. 2014;71:159–68. https://doi.org/10.1016/j.nbd.2014.08.003

    Article  CAS  PubMed  Google Scholar 

  102. Bjersing JL, Lundborg C, Bokarewa MI, Mannerkorpi K. Profile of cerebrospinal microRNAs in fibromyalgia. PLoS ONE. 2013;8(10):e78762. https://doi.org/10.1371/journal.pone.0078762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhou Q, Souba WW, Croce CM, Verne GN. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut. 2010;59(6):775–84. https://doi.org/10.1136/gut.2009.181834.

    Article  CAS  PubMed  Google Scholar 

  104. Wang WT, Zhao YN, Han BW, Hong SJ, Chen YQ. Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis. J Clin Endocrinol Metab. 2013;98(1):281–9. https://doi.org/10.1210/jc.2012-2415.

    Article  CAS  PubMed  Google Scholar 

  105. Beyer C, Zampetaki A, Lin NY, Kleyer A, Perricone C, Iagnocco A, et al. Signature of circulating microRNAs in osteoarthritis. Ann Rheum Dis. 2015;74(3):e18. https://doi.org/10.1136/annrheumdis-2013-204698.

    Article  CAS  PubMed  Google Scholar 

  106. Tao ZY, Xue Y, Li JF, Traub RJ, Cao DY. Do microRNAs modulate visceral pain? Biomed Res Int. 2018;2018:5406973. https://doi.org/10.1155/2018/5406973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Birklein F, Ajit SK, Goebel A, Perez R, Sommer C. Complex regional pain syndrome—phenotypic characteristics and potential biomarkers. Nat Rev Neurol. 2018;14(5):272–84. https://doi.org/10.1038/nrneurol.2018.20.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Bjorkman S, Taylor HS. MicroRNAs in endometriosis: biological function and emerging biomarker candidatesdagger. Biol Reprod. 2019;100(5):1135–46. https://doi.org/10.1093/biolre/ioz014.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Filkova M, Jungel A, Gay RE, Gay S. MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs. 2012;26(3):131–41. https://doi.org/10.2165/11631480-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  110. Chavan SS, Pavlov VA, Tracey KJ. Mechanisms and therapeutic relevance of neuro-immune communication. Immunity. 2017;46(6):927–42. https://doi.org/10.1016/j.immuni.2017.06.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Ciszek BP, Khan AA, Dang H, Slade GD, Smith S, Bair E, et al. MicroRNA expression profiles differentiate chronic pain condition subtypes. Transl Res. 2015;166(6):706–20. https://doi.org/10.1016/j.trsl.2015.06.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hwang CK, Wagley Y, Law PY, Wei LN, Loh HH. MicroRNAs in opioid pharmacology. J Neuroimmune Pharmacol. 2012;7(4):808–19. https://doi.org/10.1007/s11481-011-9323-2.

    Article  PubMed  Google Scholar 

  113. Li MP, Hu YD, Hu XL, Zhang YJ, Yang YL, Jiang C, et al. miRNAs and miRNA polymorphisms modify drug response. Int J Environ Res Public Health. 2016;13(11):E1096. https://doi.org/10.3390/ijerph13111096.

    Article  CAS  PubMed  Google Scholar 

  114. Willemen HLDM, Huo XJ, Mao-Ying QL, Zijlstra J, Heijnen CJ, Kavelaars A. MicroRNA-124 as a novel treatment for persistent hyperalgesia. J Neuroinflamm. 2012;9:143. https://doi.org/10.1186/1742-2094-9-143.

    Article  CAS  Google Scholar 

  115. Baumann V, Winkler J. miRNA-based therapies: strategies and delivery platforms for oligonucleotide and non-oligonucleotide agents. Future Med Chem. 2014;6(17):1967–84. https://doi.org/10.4155/fmc.14.116.

    Article  CAS  PubMed  Google Scholar 

  116. Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007;4(9):721–6. https://doi.org/10.1038/nmeth1079.

    Article  CAS  PubMed  Google Scholar 

  117. Bors LA, Erdo F. Overcoming the blood-brain barrier. Challenges and tricks for CNS drug delivery. Sci Pharm. 2019;87(1):6. https://doi.org/10.3390/scipharm87010006.

  118. Wen MM. Getting miRNA therapeutics into the target cells for neurodegenerative diseases: a mini-review. Front Mol Neurosci. 2016;9:129. https://doi.org/10.3389/fnmol.2016.00129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Simion V, Nadim WD, Benedetti H, Pichon C, Morisset-Lopez S, Baril P. Pharmacomodulation of microRNA expression in neurocognitive diseases: obstacles and future opportunities. Curr Neuropharmacol. 2017;15(2):276–90. https://doi.org/10.2174/1570159x14666160630210422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: discovering novel targets and developing specific therapy. Perspect Clin Res. 2016;7(2):68–74. https://doi.org/10.4103/2229-3485.179431.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Luchting B, Heyn J, Hinske LC, Azad SC. Expression of miRNA-124a in CD4 cells reflects response to a multidisciplinary treatment program in patients with chronic low back pain. Spine (Phila Pa 1976). 2017;42(4):E226–E33. https://doi.org/10.1097/BRS.0000000000001763.

  122. Andersen HH, Gazerani P, Duroux M. EHMTI-0122. Serum micrornas as potential biomarkers of migraine. J Headache Pain. 2014;15(Suppl 1):F1.

    Article  PubMed Central  Google Scholar 

  123. Vila-Pueyo M, Fernandez-Morales J, Torres-Ferrus M, Alvarez-Sabin J, Pozo-Rosich P. Lack of differences in microrna expression profiles of blood cells in migraine [abstract no. EHMTI-0361]. J Headache Pain. 2014;15:H3. https://doi.org/10.1186/1129-2377-15-S1-H3.

  124. Migraine Research Foundation. Final report: microRNA Expression Profile in Migraine: the microMIG study. New York: Migraine Research Foundation; 2019. https://migraineresearchfoundation.org/researchers/patricia-pozo-rosich-md-phd/. Accessed 24 Sep 2019.

  125. Tana C, Santilli F, Martelletti P, di Vincenzo A, Cipollone F, Davi G, et al. Correlation between migraine severity and cholesterol levels. Pain Pract. 2015;15(7):662–70. https://doi.org/10.1111/papr.12229.

    Article  PubMed  Google Scholar 

  126. Tana C, Tafuri E, Tana M, Martelletti P, Negro A, Affaitati G, et al. New insights into the cardiovascular risk of migraine and the role of white matter hyperintensities: is gold all that glitters? J Headache Pain. 2013;14:9. https://doi.org/10.1186/1129-2377-14-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Varma A, Jain S, Majid A, De Felice M. Central and peripheral processes in headache. Curr Opin Support Pa. 2018;12(2):142–7. https://doi.org/10.1097/Spc.0000000000000336.

    Article  Google Scholar 

  128. Olesen J, Burstein R, Ashina M, Tfelt-Hansen P. Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurol. 2009;8(7):679–90. https://doi.org/10.1016/S1474-4422(09)70090-0.

    Article  PubMed  Google Scholar 

  129. Panerai AE. Is migraine a disorder of the central nervous system? Neurol Sci. 2013;34(1):S33–5. https://doi.org/10.1007/s10072-013-1363-3.

    Article  PubMed  Google Scholar 

  130. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553–622. https://doi.org/10.1152/physrev.00034.2015.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Peng KP, May A. Migraine understood as a sensory threshold disease. Pain. 2019;160(7):1494–501. https://doi.org/10.1097/j.pain.0000000000001531.

    Article  PubMed  Google Scholar 

  132. Perry CJ, Blake P, Buettner C, Papavassiliou E, Schain AJ, Bhasin MK, et al. Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: implications for extracranial origin of headache. Ann Neurol. 2016;79(6):1000–13. https://doi.org/10.1002/ana.24665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Burstein R, Perry C, Blake P, Buettner C, Bhasin M. Abnormal expression of gene transcripts linked to inflammatory response in the periosteum of chronic migraine patients: implications to extracranial origin of headache [abstract no. EHMTI-0354]. J Headache Pain. 2014;15:K2. https://doi.org/10.1186/1129-2377-15-S1-K2.

  134. Wei Y, Nazari-Jahantigh M, Chan L, Zhu M, Heyll K, Corbalan-Campos J, et al. The microRNA-342-5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis. Circulation. 2013;127(15):1609–19. https://doi.org/10.1161/CIRCULATIONAHA.112.000736.

    Article  CAS  PubMed  Google Scholar 

  135. Rukov JL, Vinther J, Shomron N. Pharmacogenomics genes show varying perceptibility to microRNA regulation. Pharmacogenet Genom. 2011;21(5):251–62. https://doi.org/10.1097/FPC.0b013e3283438865.

    Article  CAS  Google Scholar 

  136. Fabbri M, Paone A, Calore F, Galli R, Croce CM. A new role for microRNAs, as ligands of Toll-like receptors. RNA Biol. 2013;10(2):169–74. https://doi.org/10.4161/rna.23144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Park CK, Xu ZZ, Berta T, Han QJ, Chen G, Liu XJ, et al. Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron. 2014;82(1):47–54. https://doi.org/10.1016/j.neuron.2014.02.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Fatima F, Nawaz M. Vesiculated long non-coding RNAs: offshore packages deciphering trans-regulation between cells, cancer progression and resistance to therapies. Noncoding RNA. 2017;3(1). https://doi.org/10.3390/ncrna3010010.

  139. Cannataro R, Perri M, Caroleo MC, Gallelli L, Sarro G, Cione E. Modulation of microRNAs linked to pain-migraine by ketogenic diet [abstract no. P14-007-19]. Curr Dev Nutr. 2019;3(Suppl 1):nzz052.P14-007-19. https://doi.org/10.1093/cdn/nzz052.P14-007-19.

  140. Malhotra R. Understanding migraine: potential role of neurogenic inflammation. Ann Indian Acad Neurol. 2016;19(2):175–82. https://doi.org/10.4103/0972-2327.182302.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Ramachandran R. Neurogenic inflammation and its role in migraine. Semin Immunopathol. 2018;40(3):301–14. https://doi.org/10.1007/s00281-018-0676-y.

    Article  CAS  PubMed  Google Scholar 

  142. Albrecht DS, Mainero C, Ichijo E, Ward N, Granziera C, Zurcher NR, et al. Imaging of neuroinflammation in migraine with aura: a [(11)C]PBR28 PET/MRI study. Neurology. 2019;92(17):e2038–50. https://doi.org/10.1212/WNL.0000000000007371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Spierings EL. Spreading depression, neurogenic inflammation, and the parallel theory of migraine pathogenesis. Headache. 2001;41(9):911–3.

    Article  CAS  PubMed  Google Scholar 

  144. Lewis DW. Pediatric migraine. Neurol Clin. 2009;27(2):481–501. https://doi.org/10.1016/j.ncl.2008.11.003.

    Article  PubMed  Google Scholar 

  145. Torriero R, Capuano A, Mariani R, Frusciante R, Tarantino S, Papetti L, et al. Diagnosis of primary headache in children younger than 6 years: a clinical challenge. Cephalalgia. 2017;37(10):947–54. https://doi.org/10.1177/0333102416660533.

    Article  PubMed  Google Scholar 

  146. Papetti L, Ursitti F, Moavero R, Ferilli MAN, Sforza G, Tarantino S, et al. prophylactic treatment of pediatric migraine: is there anything new in the last decade? Front Neurol. 2019;10:771. https://doi.org/10.3389/fneur.2019.00771.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Gallelli L, Cione E, Peltrone F, Siviglia S, Verano A, Chirchiglia D, et al. 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. J Clin Med. 2019;8(7):928. https://doi.org/10.3390/jcm8070928.

    Article  CAS  PubMed Central  Google Scholar 

  148. Chen XH, Li BX, Luo RC, Cai SN, Zhang C, Cao XL. Analysis of the function of microRNA-375 in humans using bioinformatics. Biomed Rep. 2017;6(5):561–6. https://doi.org/10.3892/br.2017.889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Ferroni P, Barbanti P, Spila A, Fratangeli F, Aurilia C, Fofi L, et al. Circulating biomarkers in migraine. New opportunities for precision medicine. Curr Med Chem. Epub 2018 Jun 22. https://doi.org/10.2174/0929867325666180622122938.

  150. Wang JY, Li H, Ma CM, Wang JL, Lai XS, Zhou SF. MicroRNA profiling response to acupuncture therapy in spontaneously hypertensive rats. Evid Based Compl Alternat Med. 2015;2015:204367. https://doi.org/10.1155/2015/204367.

  151. Fehlmann T, Ludwig N, Backes C, Meese E, Keller A. Distribution of microRNA biomarker candidates in solid tissues and body fluids. RNA Biol. 2016;13(11):1084–8. https://doi.org/10.1080/15476286.2016.1234658.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Jasim H, Carlsson A, Hedenberg-Magnusson B, Ghafouri B, Ernberg M. Saliva as a medium to detect and measure biomarkers related to pain. Sci Rep. 2018;8:3220. https://doi.org/10.1038/s41598-018-21131-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Johnson JJ, Loeffert AC, Stokes J, Olympia RP, Bramley H, Hicks SD. Association of salivary microRNA changes with prolonged concussion symptoms. JAMA Pediatr. 2018;172(1):65–73. https://doi.org/10.1001/jamapediatrics.2017.3884.

    Article  PubMed  Google Scholar 

  154. Hicks SD. Saliva: a new tool for concussion diagnosis? NeurologyTimes. 2018. https://www.neurologytimes.com/tbi/saliva-new-tool-concussion-diagnosis. Accessed 20 Jul 2019.

  155. Michlewski G, Caceres JF. Post-transcriptional control of miRNA biogenesis. RNA. 2019;25(1):1–16. https://doi.org/10.1261/rna.068692.118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Dwivedi S, Purohit P, Misra R, Pareek P, Goel A, Khattri S, et al. Diseases and molecular diagnostics: a step closer to precision medicine. Indian J Clin Biochem. 2017;32(4):374–98. https://doi.org/10.1007/s12291-017-0688-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Parisa Gazerani is the head of research at EMProS bio, and the scientific consultant for BalancAir, both of which are companies that focus their interest on migraine.

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Gazerani, P. Current Evidence on Potential Uses of MicroRNA Biomarkers for Migraine: From Diagnosis to Treatment. Mol Diagn Ther 23, 681–694 (2019). https://doi.org/10.1007/s40291-019-00428-8

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