
Мигрень: вопросы патогенеза и лекарственной терапии
Журнал: Журнал неврологии и психиатрии им. С.С. Корсакова. 2026;126(1):45-52.
DOI: 10.17116/jnevro202612601145
Прочитано: 1438 раз
Резюме
В обзоре обсуждается взаимосвязь механизмов патогенеза мигрени: кортикальная распространяющаяся депрессия, изменения мозгового кровообращения во время приступа мигрени и кортикальной распространяющейся депрессии, роль серотонина и кальцитонин-ген-родственного пептида в регуляции сосудов мозга и их участие в развитии приступа мигрени. Рассматриваются лекарственные препараты, используемые для лечения и профилактики мигрени, а также новые соединения, разрабатываемые для лечения и предупреждения развития приступа мигрени.
Ключевые слова
- мигрень
- кортикальная распространяющаяся депрессия
- кровоснабжение мозга
- серотонин
- триптаны
- кальцитонин-ген-родственный пептид
Дата поступления: 30.06.2025
Дата принятия в печать: 20.09.2025
Дата публикации: 09.02.2026
- Ashina M. Migraine. N Engl J Med. 2020;383(19):1866-1876. https://doi.org/10.1056/nejmra1915327
- Sudershan A, Mahajan K, Singh K, et al. The complexities of migraine: A debate among migraine researchers: A review. Clin Neurol Neurosurg. 2022;214:107136. https://doi.org/10.1016/j.clineuro.2022.107136
- Russell MB, Olesen J. Increased familial risk and evidence of genetic factor in migraine. BMJ. 1995;311(7004):541-544. https://doi.org/10.1136/bmj.311.7004.541
- Bron C, Sutherland HG, Griffiths LR. Exploring the Hereditary Nature of Migraine. Neuropsychiatr Dis Treat. 2021;17:1183-1194. https://doi.org/10.2147/ndt.s282562
- Hadjikhani N, Sanchez Del Rio M, Wu O, Moskowitz MA. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA. 2001;98(8):4687-4692. https://doi.org/10.1073/pnas.071582498
- Noseda R, Burstein R. Migraine pathophysiology: Anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 2013;154(suppl1):S44-53. https://doi.org/10.1016/j.pain.2013.07.021
- Ayata C, Jin H, Kudo C, et al. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59(4):652-661. https://doi.org/10.1002/ana.20778
- Supornsilpchai W, Sanguanrangsirikul S, Maneesri S, Srikiatkhachorn A. Serotonin depletion, cortical spreading depression and trigeminal ociception. Headache. 2006;46:34-39. https://doi.org/10.1111/j.1526-4610.2006.00310.x
- Brennan KC, Romero-Reyes MR, Lòpez Valdés HE, et al. Reduced threshold for cortical spreading depression in female mice. Ann Neurol. 2007;61(6):603-606. https://doi.org/10.1002/ana.21138
- Silberstein SD. Migraine. Lancet. 2004;363(9406):381-391. https://doi.org/10.1016/s0140-6736(04)15440-8
- Wolff HG. Headache and other head pain. New York: Oxford University. 1963.
- Shevel E. The extracranial vascular theory of migraine: an artificial controversy. J Neural Transm. 2011;118(4):525-530. https://doi.org/10.1007/s00702-010-0517-1
- Olesen J, Friberg L, Skyhoj-Olsen T, et al. Timing and topography of cerebral blood flow, aura and headache during migraine attacks. Ann Neuro. 1990;28(6):791-798. https://doi.org/10.1002/ana.410280610
- Sanchez-del Rio M, Bakker D, Wu O, et al. Perfusion weighted imaging during migraine: spontaneous visual aura and headache. Cephalalgia. 1999;19(8):701-707. https://doi.org/10.1046/j.1468-2982.1999.019008701.x
- Dalkara T, Nozari A, Moskowitz MA. Migraine aura pathophysiology: the role of blood vessels and microembolisation. Lancet Neurol. 2010;9(3):309-317. https://doi.org/10.1016/s1474-4422(09)70358-8
- Hadjikhani N, del Rio MS, Wu O, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA. 2001;98(8):4687-4692. https://doi.org/10.1073/pnas.071582498
- Pietrobon D, Striessnic J. Neurobiology of migraine. Nat Rev Neurosc. 2003;4(5):386-398. https://doi.org/10.1038/nrn1102
- Brennan KC, Charles A. An update on the blood vessel in migraine. Curr Opin Neurol. 2010;23(3):266-274. https://doi.org/10.1097/wco.0b013e32833821c1
- Cutrer FM, O’Donnell A. Recent advances in functional neuroimaging. Curr Opin Neurol. 1999;12(3):255-259. https://doi.org/10.1097/00019052-199906000-00003
- Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev. Physiol. 2013;75:365-391. https://doi.org/10.1146/annurev-physiol-030212-183717
- Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev. 2017;97(2):553-622. https://doi.org/10.1152/physrev.00034.2015
- Edvinsson L. The Trigeminovascular pathway: role of CGRP and CGR Preceptors in migraine. Headache. 2017;57(suppl2):47-55. https://doi.org/10.1111/head.13081
- Амелин А.В., Игнатов Ю.Д., Скоромец А.А. Мигрень (патогенез,
- клиника и лечение). Спб.: Мед. изд-во. 2001.
- Edvinsson L, Villalón CM, Maassen Van Den Brink A. Basic mechanisms of migraine and its acute treatment. Pharmacol Ther. 2012;136(3):319-333. https://doi.org/10.1016/j.pharmthera.2012.08.011
- Weiller C, May A, Limmroth V, et al. Brain stem activation in spontaneous human migraine attacks. Nature Med. 1995;1(7):658-660. https://doi.org/10.1038/nm0795-658
- Elhusseiny A, Hamel E. Sumatriptan elicits both constriction and https://doi.org/10.1038/sj.bjp.0703763
- Ганьшина Т.С., Бежанян С.Г., Косточка Л.М. и др. Цереброваскулярные антагонисты и агонист серотонина среди производных тропана. Экспериментальная и клиническая фармакология. 2008;71(1):26-30.
- Амелин А.В., Соколов А.Ю., Ваганов Ю.С. Мигрень. От патогенеза до лечения. М.: МЕДпресс-информ. 2022.
- Roberto G, Raschi E, Piccinni C, et al. Adverse cardiovascular events https://doi.org/10.1177/0333102414550416
- Dodick DW, Shewale AS, Lipton RB, et al. Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data. J Prim Care Community Health. 2020;11:2150132720963680. https://doi.org/10.1177/2150132720963680
- De Felice M, Ossipov MH, Wang R, et al. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann Neurol. 2010;67(3):325-337. https://doi.org/10.1002/ana.21897
- Villalón CM, Maassen Van Den Brink A. The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments. Mini Rev Med Chem. 2017;17(11):928-938. https://doi.org/10.2174/1389557516666160728121050
- Villalón CM, Centurión D. Cardiovascular responses produced by 5-hydroxytriptamine: a pharmacological update on the receptors/mechanisms involved and therapeutic implications. Naunyn Schmiedebergs Arch Pharmacol. 2007;376(1-2):45-63. https://doi.org/10.1007/s00210-007-0179-1
- Kimball RW, Friedman AP, Vallejo E. Effect of serotonin in migraine patients. Neurology. 1960;10(2):107-111. https://doi.org/10.1212/wnl.10.2.107
- Rubio-Beltrán E, Labastida-Ramírez A, Villalón CM, et al. Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018;186:88-97. https://doi.org/10.1016/j.pharmthera.2018.01.005
- Drummond PD. Tryptophan depletion increases nausea, headache and photophobia in migraine sufferers. Cephalalgia. 2006;26(10):1225-1233. https://doi.org/10.1111/j.1468-2982.2006.01212.x
- Maneepak M, Le Grand S, Srikiatkhachorn A. Serotonin depletion increases nociception-evoked trigeminal NMDA receptor phosphorylation. Headache. 2009;49(3):375-382. https://doi.org/10.1111/j.1526-4610.2009.01341.x
- Srikiatkhachorn A, Suwattanasophon C, Ruangpattanatawee A, et al. 5-HT2A receptor activation and nitric oxide synthesis: a possible mechanism determining migraine attacks. Headache. 2002;42(7):566-574. https://doi.org/10.1046/j.1526-4610.2002.02142.x
- Supornsilpchai W, le Grand SM, Srikiatkhachorn A. Involvement of pro-nociceptive 5-HT2A receptor in the pathogenesis of medication-overuse headache. Headache. 2010;50(2):185-197. https://doi.org/10.1111/j.1526-4610.2009.01591.x
- Hanko J, Hardebo JE, Kåhrström J, et al. Calcitonin gene-related peptide is present in mammalian cerebrovascular nerve fibres and dilates pial and peripheral arteries. Neurosci Lett. 1985;4;57(1):91-95. https://doi.org/10.1016/0304-3940(85)90045-x
- Russell FA, King R, Smillie SJ, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94(4):1099-1142. https://doi.org/10.1152/physrev.00034.2013
- De Boer I, Maassen Van Den Brink A, Terwindt GM. The potential danger of blocking CGRP for treating migraine in CADASIL patients. Cephalalgia 2020;40:1676-1678. https://doi.org/10.1177/0333102420941814
- Bründl E, Proescholdt M, Störr EM, et al. Endogenous calcitonin gene-related peptide in cerebrospinal fluid and early quality of life and mental health after good-grade spontaneous subarachnoid hemorrhage-a feasibility series. Neurosurg Rev. 2021;44(3):1479-1492. https://doi.org/10.1007/s10143-020-01333-z
- Luo CC, Huang CS, Ming YC, et al. Calcitonin Gene-Related Peptide Downregulates Expression of Inducible Nitride Oxide Synthase and Caspase-3 after Intestinal Ischemia-Reperfusion Injury in Rats. Pediatr Neonatol. 2016;57(6):474-479. https://doi.org/10.1016/j.pedneo.2015.10.012
- Butt E, Bernhardt M, Smolenski A, et al. Endothelial nitric-oxide synthase (type III) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases. J Biol Chem. 2000;275(7):5179-5187. https://doi.org/10.1074/jbc.275.7.5179
- Meens MJ, Mattheij NJ, van Loenen PB, et al. G-protein βγ subunits in vasorelaxing and anti-endothelinergic effects of calcitonin gene-related peptide. Br J Pharmacol. 2012;166(1):297-308. https://doi.org/10.1111/j.1476-5381.2011.01774.x
- Liu Y, Zhang S, Xue J, et al. CGRP Reduces Apoptosis of DRG Cells Induced by High-Glucose Oxidative Stress Injury through PI3K/AKT Induction of Heme Oxygenase-1 and Nrf-2 Expression. Oxid Med Cell Longev. 2019;2053149. https://doi.org/10.1155/2019/2053149
- Xiong J, Wang Z, Bai J, et al. Calcitonin gene-related peptide: a potential protective agent in cerebral ischemia-reperfusion injury. Front Neurosci. 2023;17:1184766. https://doi.org/10.3389/fnins.2023.1184766
- Luo X.-L, Yang T-L, Chen X-P, Li Y-J. Association of CALCA genetic polymorphism with essential hypertension. Chin Med J. 2008;121(15):1407-1410. https://doi.org/10.1097/00029330-200808010-00014
- Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev. 2004;84(3):903-934. https://doi.org/10.1152/physrev.00037.2003
- Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015;35(17):6619-6629. https://doi.org/10.1523/jneurosci.0373-15.2015
- Walsh DA, Mapp PI, Kelly S. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation. Br J Clin Pharmacol. 2015;80(5):965-978. https://doi.org/10.1111/bcp.12669
- Edvinsson L. Innervation and effects of dilatory neuropeptides on cerebral vessels. New aspects. Blood Vessels. 1991;28(1-3):35-45. https://doi.org/10.1159/000158841
- Odar-Cederlöf I, Theodorsson E, Eriksson CG, et al. Plasma concentrations of calcitonin gene-related peptide increase during haemodialysis: relation to blood pressure. J Intern Med. 1989;226(3):177-182. https://doi.org/10.1111/j.1365-2796.1989.tb01376.x
- Kumar A, Williamson M, Hess A, et al. Alpha-Calcitonin Gene Related Peptide: New Therapeutic Strategies for the Treatment and Prevention of Cardiovascular Disease and Migraine. Front Physiol. 2022;11:13:826122. https://doi.org/10.3389/fphys.2022.826122
- Smillie SJ, Brain SD. Calcitonin gene-related peptide (CGRP) and its role in hypertension. Neuropeptides. 2011;45(2):93-104. https://doi.org/10.1016/j.npep.2010.12.002
- Zagami AS, Goadsby PJ, Edvinsson L. Stimulation of the superior sagittal sinus in the cat causes release of vasoactive peptides. Neuropeptides. 1990;16(2):69-75. https://doi.org/10.1016/0143-4179(90)90114-e
- Messlinger K. The big CGRP flood — sources, sinks and signalling sites in the trigeminovascular system. J Headache Pain. 2018;19(1):22. https://doi.org/10.1186/s10194-018-0848-0
- Lassen LH, Haderslev PA, Jacobsen VB, et al. CGRP may play a causative role in migraine. Cephalalgia. 2002;22(1):54-61. https://doi.org/10.1046/j.1468-2982.2002.00310.x
- Lassen LH, Jacobsen VB, Haderslev PA, et al. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. J Headache Pain. 2008;9(3):151-157. https://doi.org/10.1007/s10194-008-0036-8
- Cernuda-Morollón E, Larrosa D, Ramón C, et al. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 2013;81(14):1191-1196. https://doi.org/10.1212/wnl.0b013e3182a6cb72
- Lee MJ, Lee SY, Cho S, et al. Feasibility of serum CGRP measurement as a biomarker of chronic migraine: a critical reappraisal. J Headache Pain. 2018;19(1):53. https://doi.org/10.1186/s10194-018-0883-x
- Asghar MS, Hansen AE, Kapijimpanga T, et al. Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers. Neurology. 2010;75(17):1520-1526. https://doi.org/10.1212/wnl.0b013e3181f9626a
- Simonetti M, Giniatullin R, Fabbretti E. Mechanisms mediating the enhanced gene transcription of P2X3 receptor by calcitonin gene-related peptide in trigeminal sensory neurons. J Biol Chem. 2008;283(27):18743-18752. https://doi.org/10.1074/jbc.m800296200
- Jang MU, Park JW, Kho HS, et al. Plasma and saliva levels of nerve growth factor and neuropeptides in chronic migraine patients. Oral Dis. 2011;17(2):187-193. https://doi.org/10.1111/j.1601-0825.2010.01717.x
- Maassen Van Den Brink A, Meijer J, Villalón CM, et al. Wiping Out CGRP: Potential Cardiovascular Risks. Trends Pharmacol Sci. 2016;37(9):779-788. https://doi.org/10.1016/j.tips.2016.06.002
- Kee Z, Kodji X, Brain SD. The Role of Calcitonin Gene Related Peptide (CGRP) in Neurogenic Vasodilation and Its Cardioprotective Effects. Front Physiol. 2018;9:1249. https://doi.org/10.3389/fphys.2018.01249
- Wang LH, Zhou SX, Li RC, et al. Serum levels of calcitonin gene-related peptide and substance P are decreased in patients with diabetes mellitus and coronary artery disease. J Int Med Res. 2012;40(1):134-140. https://doi.org/10.1177/147323001204000114
- Bonura A, Brunelli N, Marcosano M, et al. Calcitonin Gene-Related Peptide Systemic Effects: Embracing the Complexity of Its Biological Roles-A Narrative Review. Int J Mol Sci. 2023;24(18):13979. https://doi.org/10.3390/ijms241813979
- Ong JJY, De Felice M. Migraine Treatment: Current Acute Medications and Their Potential Mechanisms of Action. Neurotherapeutics. 2018;15(2):274-290. https://doi.org/10.1007/s13311-017-0592-1
- Tepper DE. Non-steroidal anti-inflammatories for the acute treatment of migraine. Headache. 2013;53(1):225-226. https://doi.org/10.1111/j.1526-4610.2012.02293.x
- Ahn AH, Basbaum AI. Where do triptans act in the treatment of migraine? Pain. 2005;115(1-2):1-4. https://doi.org/10.1016/j.pain.2005.03.008
- Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000;60(6):1259-1287. https://doi.org/10.2165/00003495-200060060-00003
- Rivera-Mancilla E, Maassen Van Den Brink A. Novel Pharmacological Targets of Migraine: An Overview. In: Martelletti P, Edvinsson L, eds. Novel synthetic drugs in migraine. Switzerland: Springer. 2022;1-17.
- Olesen J, Diener H-C, Husstedt IW, et al. Calcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine. N Engl J Med. 2004;350:1104-1110. https://doi.org/10.1056/nejmoa030505
- Evangelista S. Capsaicin receptor as target of calcitonin gene-related peptide in the gut. Prog Drug Res. 2014;68:259-276. https://doi.org/10.1007/978-3-0348-0828-6_10
- Liang Q, Liao X, Wu H, et al. Real-world study of adverse events associated with gepant use in migraine treatment based on the Vigi Access and U.S. Food and Drug Administration’s adverse event reporting system databases. Front Pharmacol. 2024;15:1431562. https://doi.org/10.3389/fphar.2024.1431562
- Mistry H, Naghdi S, Brown A, et al. Preventive drug treatments for adults with chronic migraine: a systematic review with economic modelling. Health Technol Assess. 2024;28(63):1-329. https://doi.org/10.3310/aywa5297
- Dalkara T, Nozari A, Moskowitz MA. Migraine aura pathophysiology: the role of blood vessels and microembolisation. Lancet Neurol. 2010;9(3):309-317. https://doi.org/10.1016/s1474-4422(09)70358-8
- Couch JR, Hassanein RS. Amitriptyline in migraine prophylaxis. Arch Neurol. 1979;36(11):695-699. https://doi.org/10.1001/archneur.1979.00500470065013
- Jackson JL, Cogbill E, Santana-Davila R, et al. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache. PLoS One. 2015;10(7):e0130733. https://doi.org/10.1371/journal.pone.0130733
- Ayata C, Jin H, Kudo C, et al. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59(4):652-661. https://doi.org/10.1002/ana.20778
- Ebersberger A. Pathophysiologie der Migräne Erklärungsmodelle zur Entstehung von Migränekopfschmerz [Pathophysiology of migraine: models to explain the generation of migraine headache]. Anaesthesist. 2002;51:661-667. https://doi.org/10.1007/s00101-002-0342-5
- Olesen J, Lassen LH. Experimental Headache Induced by Histamine, meta-Clorphenopiperazine and Reserpine? In: Olesen J, Moskowitz MA, eds. Experimental Headache Models. Frontiers in Headache Research v.5. New York, NY: Lippincott-Raven. 1995;259-263.
- Nappi RE, Sances G, Brundu B, et al. Neuroendocrine response to the serotonin agonist M-chlorophenylpiperazine in women with menstrual status migrainosus. Neuroendocrinology. 2003;78(1):52-60. https://doi.org/10.1159/000071706
- Panconesi A. Serotonin and migraine: a reconsideration of the central theory. J Headache Pain. 2008;9(5):267-276. https://doi.org/10.1007/s10194-008-0058-2
- Lin SY, Chang WJ, Lin CS, et al. Serotonin receptor 5-HT2B mediates serotonin-induced mechanical hyperalgesia. J Neurosci. 2011;31(4):1410-1418. https://doi.org/10.1523/jneurosci.4682-10.2011
- Greco R, Demartini C, De Icco R, et al. Migraine neuroscience: from experimental models to target therapy. Neurol Sci. 2020;41(suppl2):351-361. https://doi.org/10.1007/s10072-020-04808-5
- Горбунов А.А., Ганьшина Т.С., Мирзоян Р.С. Влияние тропоксина на цереброваскулярные эффекты метахлорфенилпиперазина и серотонина. Экспериментальная и клиническая фармакология. 2010;73(9):13-16.
- Ганьшина Т.С., Горбунов А.А., Гнездилова А.В. и др. Тропоксин — новое средство для лечения мигрени. Химико-фармацевтический журнал. 2016;50(1):19-23. https://doi.org/10.1007/s11094-016-1391-4
- Ганьшина Т.С. Нейромедиаторный механизм действия тропоксина в сравнении с противомигреневыми препаратами. Экспериментальная и клиническая фармакология. 2003;66(3):17-20.
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