偏头痛相关发病机制进展综述
Progress in Research on the Pathogenesis of Migraine: A Review
DOI: 10.12677/acm.2025.151045, PDF,    科研立项经费支持
作者: 王 怡, 康富丽, 蔡青青, 马璟曦*:重庆医科大学,重庆;重庆市人民医院神经内科,重庆;廖金成:重庆市人民医院神经内科,重庆;薛锐灵:重庆医科大学,重庆;重庆市人民医院康复医学科,重庆;张晖集:重庆医科大学,重庆;李佳妮:重庆医科大学附属第二医院神经内科,重庆;李 鑫:重庆市沙坪坝区人民医院神经内科,重庆
关键词: 偏头痛皮质扩散性抑制三叉神经血管学说遗传学Migraine Cortical Spreading Depression Trigeminal Neurovascular Theory Genetics
摘要: 偏头痛是一种较为常见的头痛,在世界流行疾病中排名第三,同时也是世界第二大致残疾病,可为患者带来巨大的生活负担,这就亟需对因治疗偏头痛,为患者从根本上解决头痛问题,但是目前针对偏头痛发病机制的研究结论尚不明确,各种关于偏头痛发病机制的理论层出不穷,其中就皮质扩散性抑制、三叉神经血管学说及遗传学三个理论被学术界广泛接受。本文通过回顾以往关于偏头痛发病机制的研究,总结上述三大理论的研究进展,以期明确偏头痛患者头痛背后的原因,从而为临床医生更好地治疗偏头痛提供更为有力的证据。
Abstract: Migraine is a widespread headache, ranking third in global epidemic diseases and the second most disabling disease worldwide, which burdens patients significantly. It is urgent to treat migraines and fundamentally solve the headache problem for patients, but the research conclusions on migraines’ pathogenesis are unclear. Various theories on the pathogenesis of migraine emerge endlessly, among which the academic community widely accepts cortical spreading depression, trigeminal neurovascular theory, and genetic theory. This article will review the previous research on the pathogenesis of migraine and summarize the research progress of the above three theories, clarify the reasons behind migraine patients’ headaches, and provide more powerful evidence for clinicians to treat migraine better.
文章引用:王怡, 康富丽, 廖金成, 薛锐灵, 蔡青青, 张晖集, 李佳妮, 李鑫, 马璟曦. 偏头痛相关发病机制进展综述[J]. 临床医学进展, 2025, 15(1): 323-332. https://doi.org/10.12677/acm.2025.151045

参考文献

[1] (2018) Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd Edition. Cephalalgia, 38, 1-211. [Google Scholar] [CrossRef] [PubMed]
[2] Vos, T., Abajobir, A.A., Abate, K.H., Abbafati, C., Abbas, K.M., Abd-Allah, F., et al. (2017) Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 328 Diseases and Injuries for 195 Countries, 1990-2016: A Systematic Analysis for the Global Burden of Disease Study 2016. The Lancet, 390, 1211-1259. [Google Scholar] [CrossRef] [PubMed]
[3] Feigin, V.L., Nichols, E., Alam, T., Bannick, M.S., Beghi, E., Blake, N., et al. (2019) Global, Regional, and National Burden of Neurological Disorders, 1990-2016: A Systematic Analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18, 459-480. [Google Scholar] [CrossRef] [PubMed]
[4] Ashina, M., Katsarava, Z., Do, T.P., Buse, D.C., Pozo-Rosich, P., Özge, A., et al. (2021) Migraine: Epidemiology and Systems of Care. The Lancet, 397, 1485-1495. [Google Scholar] [CrossRef] [PubMed]
[5] Leo, A.A.P. (1947) Further Observations on the Spreading Depression of Activity in the Cerebral Cortex. Journal of Neurophysiology, 10, 409-414. [Google Scholar] [CrossRef] [PubMed]
[6] Close, L.N., Eftekhari, S., Wang, M., Charles, A.C. and Russo, A.F. (2018) Cortical Spreading Depression as a Site of Origin for Migraine: Role of CGRP. Cephalalgia, 39, 428-434. [Google Scholar] [CrossRef] [PubMed]
[7] Yang, M., Ren, D., Pan, X., Li, C. and Xu, S. (2024) The Role of Astrocytes in Migraine with Cortical Spreading Depression: Protagonists or Bystanders? A Narrative Review. Pain and Therapy, 13, 679-690. [Google Scholar] [CrossRef] [PubMed]
[8] Akerman, S., Holland, P.R. and Goadsby, P.J. (2008) Mechanically-Induced Cortical Spreading Depression Associated Regional Cerebral Blood Flow Changes Are Blocked by Na+ Ion Channel Blockade. Brain Research, 1229, 27-36. [Google Scholar] [CrossRef] [PubMed]
[9] Ayata, C., Shimizu-Sasamata, M., Lo, E.H., Noebels, J.L. and Moskowitz, M.A. (1999) Impaired Neurotransmitter Release and Elevated Threshold for Cortical Spreading Depression in Mice with Mutations in the Α1a Subunit of P/Q Type Calcium Channels. Neuroscience, 95, 639-645. [Google Scholar] [CrossRef] [PubMed]
[10] Ferrari, M.D., Odink, J., Bos, K.D., Malessy, M.J.A. and Bruyn, G.W. (1990) Neuroexcitatory Plasma Amino Acids Are Elevated in Migraine. Neurology, 40, 1582-1582. [Google Scholar] [CrossRef] [PubMed]
[11] Petzold, G.C., Haack, S., von Bohlen und Halbach, O., Priller, J., Lehmann, T., Heinemann, U., et al. (2008) Nitric Oxide Modulates Spreading Depolarization Threshold in the Human and Rodent Cortex. Stroke, 39, 1292-1299. [Google Scholar] [CrossRef] [PubMed]
[12] Castillo, J., Martinez, F., Leira, R., et al. J. (1994) [Changes in Neuroexcitatory Amino Acids during and between Migraine Attacks]. Neurologia, 9, 42-45.
[13] Zielman, R., Wijnen, J.P., Webb, A., Onderwater, G.L.J., Ronen, I., Ferrari, M.D., et al. (2017) Cortical glutamate in migraine. Brain, 140, 1859-1871. [Google Scholar] [CrossRef] [PubMed]
[14] Oshinsky, M.L., Sanghvi, M.M., Maxwell, C.R., Gonzalez, D., Spangenberg, R.J., Cooper, M., et al. (2012) Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache. Headache: The Journal of Head and Face Pain, 52, 1336-1349. [Google Scholar] [CrossRef] [PubMed]
[15] Storer, R.J. and Goadsby, P.J. (1999) Trigeminovascular Nociceptive Transmission Involves N-Methyl-D-Aspartate and Non-N-Methyl-D-Aspartate Glutamate Receptors. Neuroscience, 90, 1371-1376. [Google Scholar] [CrossRef] [PubMed]
[16] Ayata, C., Jin, H., Kudo, C., Dalkara, T. and Moskowitz, M.A. (2006) Suppression of Cortical Spreading Depression in Migraine Prophylaxis. Annals of Neurology, 59, 652-661. [Google Scholar] [CrossRef] [PubMed]
[17] Bolay, H., Reuter, U., Dunn, A.K., Huang, Z., Boas, D.A. and Moskowitz, M.A. (2002) Intrinsic Brain Activity Triggers Trigeminal Meningeal Afferents in a Migraine Model. Nature Medicine, 8, 136-142. [Google Scholar] [CrossRef] [PubMed]
[18] Schain, A.J., Melo-Carrillo, A., Stratton, J., Strassman, A.M. and Burstein, R. (2019) CSD-Induced Arterial Dilatation and Plasma Protein Extravasation Are Unaffected by Fremanezumab: Implications for CGRP’s Role in Migraine with Aura. The Journal of Neuroscience, 39, 6001-6011. [Google Scholar] [CrossRef] [PubMed]
[19] Moskowitz, M., Romero, J., Reinhard, J., Melamed, E. and Pettibone, D. (1979) Neurotransmitters and the Fifth Cranial Nerve: Is There a Relation to the Headache Phase of Migraine? The Lancet, 314, 883-885. [Google Scholar] [CrossRef] [PubMed]
[20] Mulderry, P.K., Ghatki, M.A., Spokks, R.A., Jonhs, P.M., Pierson, A.M., Hamid, Q.A., et al. (1988) Differential Expression of α-CGRP and β-CGRP by Primary Sensory Neurons and Enteric Autonomic Neurons of the Rat. Neuroscience, 25, 195-205. [Google Scholar] [CrossRef] [PubMed]
[21] Eftekhari, S., Salvatore, C.A., Calamari, A., Kane, S.A., Tajti, J. and Edvinsson, L. (2010) Differential Distribution of Calcitonin Gene-Related Peptide and Its Receptor Components in the Human Trigeminal Ganglion. Neuroscience, 169, 683-696. [Google Scholar] [CrossRef] [PubMed]
[22] Weidner, C., Klede, M., Rukwied, R., Lischetzki, G., Neisius, U., Schmelz, M., et al. (2000) Acute Effects of Substance P and Calcitonin Gene-Related Peptide in Human Skin—A Microdialysis Study. Journal of Investigative Dermatology, 115, 1015-1020. [Google Scholar] [CrossRef] [PubMed]
[23] Thomsen, L.L., Kruuse, C., Iversen, H.K. and Olesen, J. (1994) A Nitric Oxide Donor (Nitroglycerin) Triggers Genuine Migraine Attacks. European Journal of Neurology, 1, 73-80. [Google Scholar] [CrossRef] [PubMed]
[24] Antonova, M., Wienecke, T., Olesen, J. and Ashina, M. (2012) Prostaglandin E2 Induces Immediate Migraine-Like Attack in Migraine Patients without Aura. Cephalalgia, 32, 822-833. [Google Scholar] [CrossRef] [PubMed]
[25] Goadsby, P.J., Edvinsson, L. and Ekman, R. (1988) Release of Vasoactive Peptides in the Extracerebral Circulation of Humans and the Cat during Activation of the Trigeminovascular System. Annals of Neurology, 23, 193-196. [Google Scholar] [CrossRef] [PubMed]
[26] Goadsby, P.J., Edvinsson, L. and Ekman, R. (1990) Vasoactive Peptide Release in the Extracerebral Circulation of Humans during Migraine Headache. Annals of Neurology, 28, 183-187. [Google Scholar] [CrossRef] [PubMed]
[27] Goadsby, P.J. and Edvinsson, L. (1993) The Trigeminovascular System and Migraine: Studies Characterizing Cerebrovascular and Neuropeptide Changes Seen in Humans and Cats. Annals of Neurology, 33, 48-56. [Google Scholar] [CrossRef] [PubMed]
[28] Cernuda-Morollón, E., Larrosa, D., Ramón, C., Vega, J., Martínez-Camblor, P. and Pascual, J. (2013) Interictal Increase of CGRP Levels in Peripheral Blood as a Biomarker for Chronic Migraine. Neurology, 81, 1191-1196. [Google Scholar] [CrossRef] [PubMed]
[29] Cernuda‐Morollón, E., Martínez‐Camblor, P., Ramón, C., Larrosa, D., Serrano‐Pertierra, E. and Pascual, J. (2014) CGRP and VIP Levels as Predictors of Efficacy of Onabotulinumtoxin Type a in Chronic Migraine. Headache: The Journal of Head and Face Pain, 54, 987-995. [Google Scholar] [CrossRef] [PubMed]
[30] Cernuda-Morollón, E., Ramón, C., Martínez-Camblor, P., Serrano-Pertierra, E., Larrosa, D. and Pascual, J. (2015) Onabotulinumtoxina Decreases Interictal CGRP Plasma Levels in Patients with Chronic Migraine. Pain, 156, 820-824. [Google Scholar] [CrossRef] [PubMed]
[31] Juhasz, G., Zsombok, T., Jakab, B., Nemeth, J., Szolcsanyi, J. and Bagdy, G. (2005) Sumatriptan Causes Parallel Decrease in Plasma Calcitonin Gene-Related Peptide (CGRP) Concentration and Migraine Headache during Nitroglycerin Induced Migraine Attack. Cephalalgia, 25, 179-183. [Google Scholar] [CrossRef] [PubMed]
[32] Cady, R.K., Vause, C.V., Ho, T.W., Bigal, M.E. and Durham, P.L. (2009) Elevated Saliva Calcitonin Gene‐related Peptide Levels during Acute Migraine Predict Therapeutic Response to Rizatriptan. Headache: The Journal of Head and Face Pain, 49, 1258-1266. [Google Scholar] [CrossRef] [PubMed]
[33] May, A. and Goadsby, P.J. (2001) Substance P Receptor Antagonists in the Therapy of Migraine. Expert Opinion on Investigational Drugs, 10, 673-678. [Google Scholar] [CrossRef] [PubMed]
[34] Edvinsson, L., McCulloch, J. and Uddman, R. (1981) Substance P: Immunohistochemical Localization and Effect Upon Cat Pial Arteries in Vitro and in Situ. The Journal of Physiology, 318, 251-258. [Google Scholar] [CrossRef] [PubMed]
[35] Salter, M.W. and Henry, J.L. (1991) Responses of Functionally Identified Neurones in the Dorsal Horn of the Cat Spinal Cord to Substance P, Neurokinin A and Physalaemin. Neuroscience, 43, 601-610. [Google Scholar] [CrossRef] [PubMed]
[36] Buzzi, M.G. and Moskowitz, M.A. (1990) The Antimigraine Drug, Sumatriptan (GR43175), Selectively Blocks Neurogenic Plasma Extravasation from Blood Vessels in Dura Mater. British Journal of Pharmacology, 99, 202-206. [Google Scholar] [CrossRef] [PubMed]
[37] Pietrobon, D. and Moskowitz, M.A. (2013) Pathophysiology of Migraine. Annual Review of Physiology, 75, 365-391. [Google Scholar] [CrossRef] [PubMed]
[38] Thörn Pérez, C., Hill, R.H., Manira, A.E. and Grillner, S. (2009) Endocannabinoids Mediate Tachykinin-Induced Effects in the Lamprey Locomotor Network. Journal of Neurophysiology, 102, 1358-1365. [Google Scholar] [CrossRef] [PubMed]
[39] Miyata, A., Jiang, L., Dahl, R.D., Kitada, C., Kubo, K., Fujino, M., et al. (1990) Isolation of a Neuropeptide Corresponding to the N-Terminal 27 Residues of the Pituitary Adenylate Cyclase Activating Polypeptide with 38 Residues (PACAP38). Biochemical and Biophysical Research Communications, 170, 643-648. [Google Scholar] [CrossRef] [PubMed]
[40] Moller, K., Zhang, Y., Håkanson, R., Luts, A., Sjölund, B., Uddman, R., et al. (1993) Pituitary Adenylate Cyclase Activating Peptide Is a Sensory Neuropeptide: Immunocytochemical and Immunochemical Evidence. Neuroscience, 57, 725-732. [Google Scholar] [CrossRef] [PubMed]
[41] Jansen-Olesen, I., Baun, M., Amrutkar, D.V., Ramachandran, R., Christophersen, D.V. and Olesen, J. (2014) PACAP-38 but Not VIP Induces Release of CGRP from Trigeminal Nucleus Caudalis via a Receptor Distinct from the PAC1 Receptor. Neuropeptides, 48, 53-64. [Google Scholar] [CrossRef] [PubMed]
[42] Ashina, M., Hansen, J.M., Do, T.P., Melo-Carrillo, A., Burstein, R. and Moskowitz, M.A. (2019) Migraine and the Trigeminovascular System—40 Years and Counting. The Lancet Neurology, 18, 795-804. [Google Scholar] [CrossRef] [PubMed]
[43] Akerman, S. and Goadsby, P.J. (2015) Neuronal PAC1 Receptors Mediate Delayed Activation and Sensitization of Trigeminocervical Neurons: Relevance to Migraine. Science Translational Medicine, 7, 308ra157. [Google Scholar] [CrossRef] [PubMed]
[44] Körtési, T., Tuka, B., Nyári, A., Vécsei, L. and Tajti, J. (2019) The Effect of Orofacial Complete Freund’s Adjuvant Treatment on the Expression of Migraine-Related Molecules. The Journal of Headache and Pain, 20, Article No. 43. [Google Scholar] [CrossRef] [PubMed]
[45] Pedersen, S.H., la Cour, S.H., Calloe, K., Hauser, F., Olesen, J., Klaerke, D.A., et al. (2019) PACAP-38 and PACAP (6-38) Degranulate Rat Meningeal Mast Cells via the Orphan MRGB3-Receptor. Frontiers in Cellular Neuroscience, 13, Article 114. [Google Scholar] [CrossRef] [PubMed]
[46] Ernstsen, C., Christensen, S.L., Rasmussen, R.H., Nielsen, B.S., Jansen-Olesen, I., Olesen, J., et al. (2022) The PACAP Pathway Is Independent of CGRP in Mouse Models of Migraine: Possible New Drug Target? Brain, 145, 2450-2460. [Google Scholar] [CrossRef] [PubMed]
[47] Hanci, F., Kilinc, Y.B., Kilinc, E., Turay, S., Dilek, M. and Kabakus, N. (2020) Plasma Levels of Vasoactive Neuropeptides in Pediatric Patients with Migraine during Attack and Attack-Free Periods. Cephalalgia, 41, 166-175. [Google Scholar] [CrossRef] [PubMed]
[48] Guo, S., Vollesen, A.L.H., Hansen, Y.B.L., Frandsen, E., Andersen, M.R., Amin, F.M., et al. (2016) Part II: Biochemical Changes after Pituitary Adenylate Cyclase-Activating Polypeptide-38 Infusion in Migraine Patients. Cephalalgia, 37, 136-147. [Google Scholar] [CrossRef] [PubMed]
[49] Liu, J., Wang, G., Dan, Y. and Liu, X. (2022) CGRP and PACAP-38 Play an Important Role in Diagnosing Pediatric Migraine. The Journal of Headache and Pain, 23, Article No. 68. [Google Scholar] [CrossRef] [PubMed]
[50] Pérez-Pereda, S., Toriello-Suárez, M., Ocejo-Vinyals, G., Guiral-Foz, S., Castillo-Obeso, J., Montes-Gómez, S., et al. (2020) Serum CGRP, VIP, and PACAP Usefulness in Migraine: A Case–control Study in Chronic Migraine Patients in Real Clinical Practice. Molecular Biology Reports, 47, 7125-7138. [Google Scholar] [CrossRef] [PubMed]
[51] Han, X., Dong, Z., Hou, L., Wan, D., Chen, M., Tang, W., et al. (2015) Interictal Plasma Pituitary Adenylate Cyclase-Activating Polypeptide Levels Are Decreased in Migraineurs but Remain Unchanged in Patients with Tension-Type Headache. Clinica Chimica Acta, 450, 151-154. [Google Scholar] [CrossRef] [PubMed]
[52] Tuka, B., Helyes, Z., Markovics, A., Bagoly, T., Szolcsányi, J., Szabó, N., et al. (2013) Alterations in PACAP-38-Like Immunoreactivity in the Plasma during Ictal and Interictal Periods of Migraine Patients. Cephalalgia, 33, 1085-1095. [Google Scholar] [CrossRef] [PubMed]
[53] Frederiksen, S.D., Bekker‐Nielsen Dunbar, M., Snoer, A.H., Deen, M. and Edvinsson, L. (2020) Serotonin and Neuropeptides in Blood from Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐analysis. Headache: The Journal of Head and Face Pain, 60, 1132-1164. [Google Scholar] [CrossRef] [PubMed]
[54] Russell, M.B. and Olesen, J. (1993) The Genetics of Migraine without Aura and Migraine with Aura. Cephalalgia, 13, 245-248. [Google Scholar] [CrossRef] [PubMed]
[55] Ziegler, D.K., Hur, Y., Bouchard, T.J., Hassanein, R.S. and Barter, R. (1998) Migraine in Twins Raised Together and Apart. Headache: The Journal of Head and Face Pain, 38, 417-422. [Google Scholar] [CrossRef] [PubMed]
[56] Russell, M.B. and Olesen, J. (1995) Increased Familial Risk and Evidence of Genetic Factor in Migraine. BMJ, 311, 541-544. [Google Scholar] [CrossRef] [PubMed]
[57] Russell, M., Iselius, L. and Olesen, J. (1995) Inheritance of Migraine Investigated by Complex Segregation Analysis. Human Genetics, 96, 726-730. [Google Scholar] [CrossRef] [PubMed]
[58] Stewart, W.F., Staffa, J., Lipton, R.B. and Ottman, R. (1997) Familial Risk of Migraine: A Population‐Based Study. Annals of Neurology, 41, 166-172. [Google Scholar] [CrossRef] [PubMed]
[59] Ulrich, V., Gervil, M., Kyvik, K.O., et al. J. (1999) The Inheritance of Migraine with Aura Estimated by Means of Structural Equation Modelling. Journal of Medical Genetics, 36, 225-227.
[60] Ulrich, V., Gervil, M., Kyvik, K.O., Olesen, J. and Russell, M.B. (1999) Evidence of a Genetic Factor in Migraine with Aura: A Population-Based Danish Twin Study. Annals of Neurology, 45, 242-246. [Google Scholar] [CrossRef
[61] Polderman, T.J.C., Benyamin, B., de Leeuw, C.A., Sullivan, P.F., van Bochoven, A., Visscher, P.M., et al. (2015) Meta-analysis of the Heritability of Human Traits Based on Fifty Years of Twin Studies. Nature Genetics, 47, 702-709. [Google Scholar] [CrossRef] [PubMed]
[62] Russell, M., Iselius, L. and Olesen, J. (1996) Migraine without Aura and Migraine with Aura Are Inherited Disorders. Cephalalgia, 16, 305-309. [Google Scholar] [CrossRef] [PubMed]
[63] Stewart, W.F., Bigal, M.E., Kolodner, K., Dowson, A., Liberman, J.N. and Lipton, R.B. (2006) Familial Risk of Migraine. Neurology, 66, 344-348. [Google Scholar] [CrossRef] [PubMed]
[64] Russell, M.B., Ulrich, V., Gervil, M. and Olesen, J. (2002) Migraine without Aura and Migraine with Aura Are Distinct Disorders. a Population‐based Twin Survey: Variation by Proband Age at Onset and Headache Severity. Headache: The Journal of Head and Face Pain, 42, 332-336. [Google Scholar] [CrossRef] [PubMed]
[65] D’Amico, D., Leone, M., Macciardi, F., Valentini, S. and Bussone, G. (1991) Genetic Transmission of Migraine without Aura: A Study of 68 Families. The Italian Journal of Neurological Sciences, 12, 581-584. [Google Scholar] [CrossRef] [PubMed]
[66] Mochi, M., Sangiorgi, S., Cortelli, P., Carelli, V., Scapoli, C., Crisci, M., et al. (1993) Testing Models for Genetic Determination in Migraine. Cephalalgia, 13, 389-394. [Google Scholar] [CrossRef] [PubMed]
[67] Gormley, P., Anttila, V., Winsvold, B.S., Palta, P., Esko, T., Pers, T.H., et al. (2016) Meta-Analysis of 375,000 Individuals Identifies 38 Susceptibility Loci for Migraine. Nature Genetics, 48, 856-866. [Google Scholar] [CrossRef] [PubMed]
[68] Wieser, T., Pascual, J., Oterino, A., Soso, M., Barmada, M. and Gardner, K.L. (2010) A Novel Locus for Familial Migraine on XP22. Headache: The Journal of Head and Face Pain, 50, 955-962. [Google Scholar] [CrossRef] [PubMed]
[69] Lea, R.A., Nyholt, D.R., Curtain, R.P., Ovcaric, M., Sciascia, R., Bellis, C., et al. (2005) A Genome-Wide Scan Provides Evidence for Loci Influencing a Severe Heritable Form of Common Migraine. Neurogenetics, 6, 67-72. [Google Scholar] [CrossRef] [PubMed]
[70] Wessman, M., Kallela, M., Kaunisto, M.A., Marttila, P., Sobel, E., Hartiala, J., et al. (2002) A Susceptibility Locus for Migraine with Aura, on Chromosome 4q24. The American Journal of Human Genetics, 70, 652-662. [Google Scholar] [CrossRef] [PubMed]
[71] Lea, R.A., Shepherd, G.A., Curtain, R.P., Nyholt, D.R., Quinlan, S., Brimage, P.J., et al. (2002) A Typical Migraine Susceptibility Region Localizes to Chromosome 1q31. Neurogenetics, 4, 17-22. [Google Scholar] [CrossRef] [PubMed]
[72] Hautakangas, H., Winsvold, B.S., Ruotsalainen, S.E., Bjornsdottir, G., Harder, A.V.E., Kogelman, L.J.A., et al. (2022) Genome-Wide Analysis of 102,084 Migraine Cases Identifies 123 Risk Loci and Subtype-Specific Risk Alleles. Nature Genetics, 54, 152-160. [Google Scholar] [CrossRef] [PubMed]
[73] Rasmussen, A.H., Kogelman, L.J.A., Kristensen, D.M., Chalmer, M.A., Olesen, J. and Hansen, T.F. (2020) Functional Gene Networks Reveal Distinct Mechanisms Segregating in Migraine Families. Brain, 143, 2945-2956. [Google Scholar] [CrossRef] [PubMed]
[74] Khan, J., Al Asoom, L., Al Sunni, A., Rafique, N., Latif, R., Alabdali, M., et al. (2022) Whole-exome Sequencing Reveals Migraine-Associated Novel Functional Variants in Arab Ancestry Females: A Pilot Study. Brain Sciences, 12, Article 1429. [Google Scholar] [CrossRef] [PubMed]
[75] Techlo, T.R., Rasmussen, A.H., Møller, P.L., Bøttcher, M., Winther, S., Davidsson, O.B., et al. (2020) Familial Analysis Reveals Rare Risk Variants for Migraine in Regulatory Regions. Neurogenetics, 21, 149-157. [Google Scholar] [CrossRef] [PubMed]
[76] Carvalho, E., Dias, A., Sousa, A., Lopes, A.M., Martins, S., Pinto, N., et al. (2022) A High Methylation Level of a Novel −284 bp CpG Island in the RAMP1 Gene Promoter Is Potentially Associated with Migraine in Women. Brain Sciences, 12, Article 526. [Google Scholar] [CrossRef] [PubMed]
[77] Khan, J., Asoom, L.I.A., Sunni, A.A., Rafique, N., Latif, R., Saif, S.A., et al. (2021) Genetics, Pathophysiology, Diagnosis, Treatment, Management, and Prevention of Migraine. Biomedicine & Pharmacotherapy, 139, Article ID: 111557. [Google Scholar] [CrossRef] [PubMed]
[78] Giffin, N.J., Ruggiero, L., Lipton, R.B., Silberstein, S.D., Tvedskov, J.F., Olesen, J., et al. (2003) Premonitory Symptoms in Migraine. Neurology, 60, 935-940. [Google Scholar] [CrossRef] [PubMed]
[79] Maniyar, F.H., Sprenger, T., Monteith, T., Schankin, C. and Goadsby, P.J. (2013) Brain Activations in the Premonitory Phase of Nitroglycerin-Triggered Migraine Attacks. Brain, 137, 232-241. [Google Scholar] [CrossRef] [PubMed]
[80] Lauritzen, M., Dreier, J.P., Fabricius, M., Hartings, J.A., Graf, R. and Strong, A.J. (2010) Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury. Journal of Cerebral Blood Flow & Metabolism, 31, 17-35. [Google Scholar] [CrossRef] [PubMed]
[81] Olesen, J., Larsen, B. and Lauritzen, M. (1981) Focal Hyperemia Followed by Spreading Oligemia and Impaired Activation of RCBF in Classic Migraine. Annals of Neurology, 9, 344-352. [Google Scholar] [CrossRef] [PubMed]
[82] Charles, A. (2018) The Pathophysiology of Migraine: Implications for Clinical Management. The Lancet Neurology, 17, 174-182. [Google Scholar] [CrossRef] [PubMed]
[83] Dodick, D.W. (2018) A Phase‐by‐phase Review of Migraine Pathophysiology. Headache: The Journal of Head and Face Pain, 58, 4-16. [Google Scholar] [CrossRef] [PubMed]
[84] Pavlovic, J.M., Buse, D.C., Sollars, C.M., Haut, S. and Lipton, R.B. (2014) Trigger Factors and Premonitory Features of Migraine Attacks: Summary of Studies. Headache: The Journal of Head and Face Pain, 54, 1670-1679. [Google Scholar] [CrossRef] [PubMed]