<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mes</journal-id><journal-title-group><journal-title xml:lang="ru">Экстремальная биомедицина</journal-title><trans-title-group xml:lang="en"><trans-title>Extreme Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">3033-8964</issn><issn pub-type="epub">3033-8972</issn><publisher><publisher-name>Centre for Strategic Planning of the Federal Medical and Biological Agency</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.47183/mes.2026-529</article-id><article-id custom-type="elpub" pub-id-type="custom">mes-529</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>АВИАЦИОННАЯ И КОСМИЧЕСКАЯ МЕДИЦИНА</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>AVIATION &amp; SPACE MEDICINE</subject></subj-group></article-categories><title-group><article-title>Влияние 365-суточной изоляции на концентрацию биогенных аминов и маркеров головной боли: проспективное когортное исследование</article-title><trans-title-group xml:lang="en"><trans-title>Impact of 365-day isolation on biogenic amine levels and headache-related biomarkers: A prospective cohort study</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0009-1738-493X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Седов</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Sedov</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Седов Евгений Андреевич</p><p>Москва</p></bio><bio xml:lang="en"><p>Eugene A. Sedov</p><p>Moscow</p></bio><email xlink:type="simple">sedov.gf@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0879-889X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Васильева</surname><given-names>Г. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Vassilieva</surname><given-names>G. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Васильева Галина Юрьевна, канд. мед. наук</p><p>Москва</p></bio><bio xml:lang="en"><p>Galina Yu. Vassilieva, Cand. Sci. (Med.)</p><p>Moscow</p></bio><email xlink:type="simple">galvassilieva@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-6130-9770</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колесников</surname><given-names>Д. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolesnikov</surname><given-names>D. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Колесников Дмитрий Юрьевич</p><p>Москва</p></bio><bio xml:lang="en"><p>Dmitrii Yu. Kolesnikov</p><p>Moscow</p></bio><email xlink:type="simple">dmitrs08@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5381-1013</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гордиенко</surname><given-names>К. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Gordienko</surname><given-names>K. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гордиенко Кирилл Владимирович</p><p>Москва</p></bio><bio xml:lang="en"><p>Kirill V. Gordienko</p><p>Moscow</p></bio><email xlink:type="simple">k.vl.gordienko@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9567-3317</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гимадиев</surname><given-names>Р. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Gimadiev</surname><given-names>R. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гимадиев Ринат Рашитович</p><p>Москва</p></bio><bio xml:lang="en"><p>Rinat R. Gimadiev</p><p>Moscow</p></bio><email xlink:type="simple">rinat_mbf@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Институт медико-биологических проблем Российской академии наук</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Biomedical Problems of the Russian Academy of Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>16</day><month>09</month><year>2026</year></pub-date><volume>0</volume><issue>0</issue><issue-title>Online First</issue-title><elocation-id>529</elocation-id><permissions><copyright-statement>Copyright &amp;#x00A9; Седов Е.А., Васильева Г.Ю., Колесников Д.Ю., Гордиенко К.В., Гимадиев Р.Р., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Седов Е.А., Васильева Г.Ю., Колесников Д.Ю., Гордиенко К.В., Гимадиев Р.Р.</copyright-holder><copyright-holder xml:lang="en">Sedov E.A., Vassilieva G.Y., Kolesnikov D.Y., Gordienko K.V., Gimadiev R.R.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.extrememedicine.ru/jour/article/view/529">https://www.extrememedicine.ru/jour/article/view/529</self-uri><abstract><sec><title>Введение</title><p>Введение. При подготовке к длительным космическим полетам критически важно оценивать влияние изоляции на физическое и психоэмоциональное состояние экипажа. Головная боль — один из самых частых симптомов стресса в замкнутом пространстве, в ее патогенезе ключевую роль играют биогенные амины и нейропептиды (в частности, субстанция P и пептид, связанный с кальцитонином — CGRP), служащие маркерами нейроэндокринной реакции организма.</p></sec><sec><title>Цель</title><p>Цель. Оценка влияния 365-суточной изоляции в гермообъекте на уровень биогенных аминов и маркеров головной боли для разработки эффективных стратегий профилактики и коррекции цефалгии у членов экипажей длительных космических миссий.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. В изоляционном эксперименте SIRIUS-23 на базе ГНЦ РФ — ИМБП РАН приняли участие 6 человек (4 женщины, 2 мужчин; средний возраст 30,8 ± 4,3 года). Обследование (забор проб крови и мочи) у участников эксперимента SIRIUS-23 проведено в: фоновый период (–7-е сутки), на 20, 45, 86, 112,146, 175, 210, 240, 270, 301, 336, 364-е сутки и в период последействия (+14-е сутки). Методами высокоэффективной жидкостной хроматографии и иммуноферментного анализа исследовали динамику уровней адреналина, норадреналина, дофамина, серотонина, CGRP, субстанции P и метаболитов (VMA, HVA, 5-HIAA) в плазме/ сыворотке крови и суточной моче. Наличие головной боли и психоэмоциональное состояние оценивали с помощью анкет и визуальной аналоговой шкалы (ВАШ). Статистический анализ проведен с помощью программного обеспечения GraphPаd Prism 8.</p></sec><sec><title>Результаты</title><p>Результаты. Выявлена значимая динамика катехоламинов: уровни адреналина и норадреналина были достоверно выше в первой половине эксперимента с тенденцией к снижению во второй (начиная с 210-х суток). Концентрация метаболитов (VMA, 5-HIAA) у некоторых участников, напротив, возрастала во второй половине изоляции. Статистически значимых различий в концентрации дофамина у участников эксперимента в различных периодах изоляции выявлено не было, однако были обнаружены значения, выходящие за пределы референтного диапазона (0–100 пг/мл): 264,18; 118,01; 136,03; 101,89 пг/мл. На 146-е сутки эксперимента отмечено увеличение концентрации серотонина (референтный диапазон 50–220 нг/мл) у половины испытуемых: 297,87; 334,84 и 375,93 нг/мл, а значения для всех испытуемых в этот день были выше, нежели в фоновый период и в период последействия. Головные боли носили преимущественно эпизодический характер слабой интенсивности. Однако во второй половине изоляции частота и интенсивность приступов головной боли возросли (до 8–10 баллов), основным триггером являлся эмоциональный стресс. Отмечены жалобы на усиление боли при физической активности и сенсорных стимулах. При этом статистически значимых изменений или экстремальных выбросов в концентрациях нейропептидов CGRP и субстанции P между фоновыми данными и сессиями изоляции не обнаружено.</p></sec><sec><title>Выводы</title><p>Выводы. Годовая изоляция вызывает изменения в метаболизме биогенных аминов, что отражает процессы адаптации к стрессу. Однако достоверных изменений концентрации специфических маркеров головной боли (CGRP и субстанции P) не выявлено. Полученные данные подчеркивают необходимость контроля факторов среды обитания (температура, освещение, газовый состав, физическая активность, питание) при интерпретации нейрохимических биомаркеров в замкнутых пространствах, так как мониторинг триггеров является основой профилактики цефалгии в длительных изоляционных экспериментах и будущих межпланетных миссиях.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Preparation for long-duration spaceflights requires assessing the impact of isolation stress on the crew’s physiological and psychological status. One of the most common symptoms is headache, driven by biogenic amines and neuropeptides — particularly substance P and calcitonin gene-related peptide (CGRP) — which serve as markers of the body’s neuroendocrine response.</p></sec><sec><title>Objective</title><p>Objective. To assess the impact of 365-day isolation in a sealed facility on the levels of biogenic amines and headache markers and to develop effective prevention and correction strategies for cephalalgia in crew members during long-duration space missions.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. The SIRIUS-23 isolation experiment was conducted at the Institute of Biomedical Problems of the Russian Academy of Sciences (IMBP RAS) with the participation of 6 individuals (4 females, 2 males; mean age 30.8 ± 4.3 years). Blood and urine sampling was performed during the baseline period (day –7), at multiple isolation time points (days 20, 45, 86, 112, 146, 175, 210, 240, 270, 301, 336, and 364), and during the after-effect period (day +14). High-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate changes in the levels of adrenaline, noradrenaline, dopamine, serotonin, CGRP, substance P, and metabolites (VMA, HVA, and 5-HIAA) in plasma/serum and 24-h urine. Headache intensity and psychoemotional state were assessed using questionnaires and a visual analogue scale (VAS). Statistical analysis was performed using GraphPad Prism 8 software.</p></sec><sec><title>Results</title><p>Results. Significant variations in catecholamine levels were documented. Adrenaline and noradrenaline levels were significantly higher during the first half of the experiment, with a downward tendency in the second half (starting from day 210). In contrast, metabolite levels (VMA and 5-HIAA) increased in some participants during the second half. Dopamine levels showed no statistically significant differences across isolation phases; however, individual values exceeding the reference range (0–100 pg/mL) were observed (264.18, 118.01, 136.03, and 101.89 pg/mL). On day 146 of the experiment, an increase in serotonin level (reference range: 50–220 ng/mL) was observed in half of the subjects (297.87, 334.84, and 375.93 ng/mL). The values for all subjects on that day were higher than those recorded during the baseline and after-effect periods. Headaches were predominantly episodic and of mild intensity. In the second half of isolation, the frequency and intensity of headache attacks increased, with VAS scores reaching 8–10 points; emotional stress was the primary trigger. Pain exacerbation during physical activity and exposure to sensory stimuli was reported by participants. At the same time, no statistically significant changes or extreme outliers were observed in CGRP and substance P levels when comparing baseline data with measurements obtained during isolation.</p></sec><sec><title>Conclusions</title><p>Conclusions. One-year isolation altered the metabolism of biogenic amines, reflecting adaptation to stress; however, no significant changes were observed in the levels of specific headache markers (CGRP and substance P). These findings highlight the importance of accounting for environmental factors (temperature, lighting, gas composition, physical activity, and nutrition) when interpreting neurochemical biomarkers in confined environments. Managing these triggers is essential for preventing cephalalgia in long-duration isolation experiments and future interplanetary missions.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>нейроспецифические биомаркеры</kwd><kwd>космический полет</kwd><kwd>головная боль</kwd><kwd>биогенные амины</kwd><kwd>CGRP</kwd><kwd>субстанция P</kwd><kwd>изоляция</kwd></kwd-group><kwd-group xml:lang="en"><kwd>neuro-specific biomarkers</kwd><kwd>spaceflight</kwd><kwd>headache</kwd><kwd>biogenic amines</kwd><kwd>CGRP</kwd><kwd>substance P</kwd><kwd>isolation</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках государственного задания Министерства науки и высшего образования Российской Федерации (№ FMFR-2024-0039).</funding-statement><funding-statement xml:lang="en">The work was carried out within the framework of the state assignment of the Ministry of Science and Higher Education of the Russian Federation (No. FMFR-2024-0039).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Шток ВН. Головная боль. М.: Медицина; 1988. EDN: QLORZL</mixed-citation><mixed-citation xml:lang="en">Shtok VN. Headache. Moscow: Meditsina; 1988 (In Russ.). EDN: QLORZL</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Van Ombergen A, Jillings S, Jeurissen B, Tomilovskaya E, Ruhl RM, Rumshiskaya A, et al. Brain tissue-volume changes in cosmonauts. The New England Journal of Medicine. 2018;379(17):1678–80. https://doi.org/10.1056/NEJMc1809011</mixed-citation><mixed-citation xml:lang="en">Van Ombergen A, Jillings S, Jeurissen B, Tomilovskaya E, Ruhl RM, Rumshiskaya A, et al. Brain tissue-volume changes in cosmonauts. The New England Journal of Medicine. 2018;379(17):1678–80. https://doi.org/10.1056/NEJMc1809011</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. The New England Journal of Medicine. 2017;377(18):1746–53. https://doi.org/10.1056/NEJMoa1705129</mixed-citation><mixed-citation xml:lang="en">Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. The New England Journal of Medicine. 2017;377(18):1746–53. https://doi.org/10.1056/NEJMoa1705129</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Jillings S, Van Ombergen A, Tomilovskaya E, Rumshiskaya A, Litvinova L, Nosikova I, et al. Macro- and microstructural changes in cosmonauts’ brains after long-duration spaceflight. Science Advances. 2020;6(36):eaaz9488. https://doi.org/10.1126/sciadv.aaz9488</mixed-citation><mixed-citation xml:lang="en">Jillings S, Van Ombergen A, Tomilovskaya E, Rumshiskaya A, Litvinova L, Nosikova I, et al. Macro- and microstructural changes in cosmonauts’ brains after long-duration spaceflight. Science Advances. 2020;6(36):eaaz9488. https://doi.org/10.1126/sciadv.aaz9488</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Zu Eulenburg P, Buchheim JI, Ashton NJ, Vassilieva G, Blennow K, Zetterberg H, et al. Changes in blood biomarkers of brain injury and degeneration following long-duration spaceflight. JAMA Neurology. 2021;78(12):1525–7. https://doi.org/10.1001/jamaneurol.2021.3589</mixed-citation><mixed-citation xml:lang="en">Zu Eulenburg P, Buchheim JI, Ashton NJ, Vassilieva G, Blennow K, Zetterberg H, et al. Changes in blood biomarkers of brain injury and degeneration following long-duration spaceflight. JAMA Neurology. 2021;78(12):1525–7. https://doi.org/10.1001/jamaneurol.2021.3589</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Van Oosterhout WPJ, Perenboom MJL, Terwindt GM, Ferrari MD, Vein AA. Frequency and clinical features of space headache experienced by astronauts during long-haul space flights. Neurology. 2024;102(7):e209224. https://doi.org/10.1212/WNL.0000000000209224</mixed-citation><mixed-citation xml:lang="en">Van Oosterhout WPJ, Perenboom MJL, Terwindt GM, Ferrari MD, Vein AA. Frequency and clinical features of space headache experienced by astronauts during long-haul space flights. Neurology. 2024;102(7):e209224. https://doi.org/10.1212/WNL.0000000000209224</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Vein AA, Koppen H, Haan J, Terwindt GM, Ferrari MD. Space headache: a new secondary headache. Cephalalgia. 2009;29(6):683–6. https://doi.org/10.1111/j.1468-2982.2008.01775.x</mixed-citation><mixed-citation xml:lang="en">Vein AA, Koppen H, Haan J, Terwindt GM, Ferrari MD. Space headache: a new secondary headache. Cephalalgia. 2009;29(6):683–6. https://doi.org/10.1111/j.1468-2982.2008.01775.x</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Noskov VB. Water and salt metabolism during space flights. Human Physiology. 2015;41(7):683–8. https://doi.org/10.1134/S0362119715070154</mixed-citation><mixed-citation xml:lang="en">Noskov VB. Water and salt metabolism during space flights. Human Physiology. 2015;41(7):683–8. https://doi.org/10.1134/S0362119715070154</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Носков ВБ. Адаптация водно-электролитного метаболизма к условиям космического полета и при его имитации. Физиология человека. 2013;39(5):119–25. https://doi.org/10.7868/S0131164613050111</mixed-citation><mixed-citation xml:lang="en">Noskov VB. Adaptation of water-electrolyte metabolism to the conditions of space flight and its simulation. Human Physiology. 2013;39(5):119–25 (In Russ.). https://doi.org/10.7868/S0131164613050111</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Ларина ИМ. Гормональная регуляция метаболизма в организме человека в условиях микрогравитации и при моделировании ее физиологических эффектов (обзор). Авиакосмическая и экологическая медицина. 2003;37(2):32–41. EDN: PENVYH</mixed-citation><mixed-citation xml:lang="en">Larina IM. Hormonal regulation of metabolism in the human body under microgravity and simulation of its physiological effects (review). Aerospace and Environmental Medicine. 2003;37(2):32–41 (In Russ.). EDN: PENVYH</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Носков ВБ. Механизмы волюморегуляции при действии факторов космического полета. Авиакосмическая и экологическая медицина. 2000;34(4):3–8. EDN: SXRFOH</mixed-citation><mixed-citation xml:lang="en">Noskov VB. Mechanisms of volume regulation under the action of space flight factors. Aerospace and Environmental Medicine. 2000;34(4):3–8 (In Russ.). EDN: SXRFOH</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Macho L, Koska J, Ksinantova L, Pacak K, Hoff T, Noskov VB, et al. The response of endocrine system to stress loads during space flight in human subject. Advances in Space Research. 2003;31(6):1605–10. https://doi.org/10.1016/S0273-1177(03)00097-8</mixed-citation><mixed-citation xml:lang="en">Macho L, Koska J, Ksinantova L, Pacak K, Hoff T, Noskov VB, et al. The response of endocrine system to stress loads during space flight in human subject. Advances in Space Research. 2003;31(6):1605–10. https://doi.org/10.1016/S0273-1177(03)00097-8</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Алферова ИВ, Михайлов ВМ, Турчанинова ВФ, Фомина ГА, Яров АС. Пережимные браслеты как средство профилактики неблагоприятных влияний невесомости. В кн.: Орбитальная станция «Мир». Том 1. М.: Изд-во ООО «Аником»; 2001.</mixed-citation><mixed-citation xml:lang="en">Alferova IV, Mikhailov VM, Turchaninova VF, Fomina GA, Yarov AS. Compression bracelets as a means of preventing the adverse effects of weightlessness. In: Orbital station “Mir”. Vol. 1. Moscow: Anikom; 2001 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Gontcharov IB, Kovachevich IV, Pool SL, Navinkov AL, Barratt MR. Medical care system for NASA-Mir spaceflights. Aviation, Space, and Environmental Medicine. 2002;73(12):1219–23. PMID: 12498552</mixed-citation><mixed-citation xml:lang="en">Gontcharov IB, Kovachevich IV, Pool SL, Navinkov AL, Barratt MR. Medical care system for NASA-Mir spaceflights. Aviation, Space, and Environmental Medicine. 2002;73(12):1219–23. PMID: 12498552</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Kanas N, Salnitskiy V, Gushin V, Weiss DS, Grund EM, Flynn C, et al. Asthenia—does it exist in space? Psychosomatic Medicine. 2001;63(6):874–80. https://doi.org/10.1097/00006842-200111000-00004</mixed-citation><mixed-citation xml:lang="en">Kanas N, Salnitskiy V, Gushin V, Weiss DS, Grund EM, Flynn C, et al. Asthenia—does it exist in space? Psychosomatic Medicine. 2001;63(6):874–80. https://doi.org/10.1097/00006842-200111000-00004</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Данилов АБ, Данилов АБ. Управление болью. Биопсихосоциальный подход. М.: АММ ПРЕСС; 2016.</mixed-citation><mixed-citation xml:lang="en">Danilov AB, Danilov AlB. Pain management. Biopsychosocial approach. Moscow: AMM PRESS; 2016 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Лебедева ЕР, Кобзева НР, Цыпушкина ТС, Филимоно ва ПА, Флягина КИ, Цветкова НИ и др. Распространенность головных болей у студентов медицинского университета согласно Международной классификации головных болей 3-го пересмотра. Российский журнал боли. 2015;2:17–22.</mixed-citation><mixed-citation xml:lang="en">Lebedeva ER, Kobzeva NR, Tsypushkina TS, Filimonova PA, Fljagina KI, Tsvetkova NI, et al. Prevalence of headaches among medical university students according to the International Classification of Headache Disorders, 3rd ed. Russian Journal of Pain. 2015;2:17–22 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Brem C, Lutz J, Vollmar C, Feuerecker M, Strewe C, Nichiporuk I, et al. Changes of brain DTI in healthy human subjects after 520 days isolation and confinement on a simulated mission to Mars. Life Sciences in Space Research. 2020;24:83–90. https://doi.org/10.1016/j.lssr.2019.09.004</mixed-citation><mixed-citation xml:lang="en">Brem C, Lutz J, Vollmar C, Feuerecker M, Strewe C, Nichiporuk I, et al. Changes of brain DTI in healthy human subjects after 520 days isolation and confinement on a simulated mission to Mars. Life Sciences in Space Research. 2020;24:83–90. https://doi.org/10.1016/j.lssr.2019.09.004</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Demiot C, Dignat-George F, Fortrat JO, Sabatier F, Gharib C, Larina I, et al. WISE 2005: chronic bed rest impairs microcirculatory endothelium in women. American Journal of Physiology — Heart and Circulatory Physiology. 2007;293(5):H3159–64. https://doi.org/10.1152/ajpheart.00591.2007</mixed-citation><mixed-citation xml:lang="en">Demiot C, Dignat-George F, Fortrat JO, Sabatier F, Gharib C, Larina I, et al. WISE 2005: chronic bed rest impairs microcirculatory endothelium in women. American Journal of Physiology — Heart and Circulatory Physiology. 2007;293(5):H3159–64. https://doi.org/10.1152/ajpheart.00591.2007</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Пастушкова ЛХ, Каширина ДН, Кононихин АС, Бржозовский АГ, Иванисенко ВА, Тийс ЕС и др. Влияние длительных космических полетов на белки мочи, функционально связанные с эндотелием. Физиология человека. 2018;44(1):60–7. https://doi.org/10.7868/S0131164618010095</mixed-citation><mixed-citation xml:lang="en">Pastushkova LKh, Kashirina DN, Kononikhin AS, Brzhozovsky AG, Ivanisenko VA, Tiis ES, et al. Effect of long-duration space flights on urine proteins functionally associated with the endothelium. Human Physiology. 2018;44(1):60–7 (In Russ.). https://doi.org/10.7868/S0131164618010095</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Feuerecker M, van Oosterhout WPJ, Feuerecker B, Matzel S, Schelling G, Rehm M, et al. Headache under simulated microgravity is related to endocrine, fluid distribution, and tight junction changes. Pain. 2016;157(5):1072–8. https://doi.org/10.1097/j.pain.0000000000000481</mixed-citation><mixed-citation xml:lang="en">Feuerecker M, van Oosterhout WPJ, Feuerecker B, Matzel S, Schelling G, Rehm M, et al. Headache under simulated microgravity is related to endocrine, fluid distribution, and tight junction changes. Pain. 2016;157(5):1072–8. https://doi.org/10.1097/j.pain.0000000000000481</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Mashaghi A, Marmalidou A, Tehrani M, Grace PM, Pothoulakis C, Dana R. Neuropeptide substance P and the immune response. Cellular and Molecular Life Sciences. 2016;73(22):4249–64. https://doi.org/10.1007/s00018-016-2293-z</mixed-citation><mixed-citation xml:lang="en">Mashaghi A, Marmalidou A, Tehrani M, Grace PM, Pothoulakis C, Dana R. Neuropeptide substance P and the immune response. Cellular and Molecular Life Sciences. 2016;73(22):4249–64. https://doi.org/10.1007/s00018-016-2293-z</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Табеева ГР. Патофизиология мигрени. Боль. 2007;4:1–8. EDN: IJRGPT</mixed-citation><mixed-citation xml:lang="en">Tabeeva GR. Pathophysiology of migraine. Pain. 2007;4:1–8 (In Russ.). EDN: IJRGPT</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Russo AF, Hay DL. CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond. Physiological Reviews. 2023;103(2):1565–644. https://doi.org/10.1152/physrev.00059.2021</mixed-citation><mixed-citation xml:lang="en">Russo AF, Hay DL. CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond. Physiological Reviews. 2023;103(2):1565–644. https://doi.org/10.1152/physrev.00059.2021</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Пономарёв СА, Белаковский МС. Международный научный изоляционный эксперимент SIRIUS-23. Авиакосмическая и экологическая медицина. 2025;59(7):5–12. https://doi.org/10.21687/0233-528X-2025-59-7-5-12</mixed-citation><mixed-citation xml:lang="en">Ponomarev SA, Belakovskiy MS. The international SIRIUS-23 isolation experiment: an overview. Aerospace and Environmental Medicine. 2023;103(2):1565–644 (In Russ.). https://doi.org/10.21687/0233-528X-2025-59-7-5-12</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">D’Andrea G, Gucciardi A, Leon A. Elusive amines: migraine depends on biochemical abnormalities. Neurological Sciences. 2022;43(11):6299–304. https://doi.org/10.1007/s10072-022-06241-2</mixed-citation><mixed-citation xml:lang="en">D’Andrea G, Gucciardi A, Leon A. Elusive amines: migraine depends on biochemical abnormalities. Neurological Sciences. 2022;43(11):6299–304. https://doi.org/10.1007/s10072-022-06241-2</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Barbanti P, Fofi L, Aurilia C, Egeo G. Dopaminergic symptoms in migraine. Neurological Sciences. 2013;34(Suppl 1):S67–70. https://doi.org/10.1007/s10072-013-1415-8</mixed-citation><mixed-citation xml:lang="en">Barbanti P, Fofi L, Aurilia C, Egeo G. Dopaminergic symptoms in migraine. Neurological Sciences. 2013;34(Suppl 1):S67–70. https://doi.org/10.1007/s10072-013-1415-8</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Kim DJ, Jassar H, Lim M, DaSilva AF. Dopaminergic regulation of reward system connectivity underpins pain and emotional suffering in migraine. Journal of Pain Research. 2021;14:631–43. https://doi.org/10.2147/JPR.S296540</mixed-citation><mixed-citation xml:lang="en">Kim DJ, Jassar H, Lim M, DaSilva AF. Dopaminergic regulation of reward system connectivity underpins pain and emotional suffering in migraine. Journal of Pain Research. 2021;14:631–43. https://doi.org/10.2147/JPR.S296540</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Vila-Pueyo M, Strother LC, Kefel M, Goadsby PJ, Holland PR. Divergent influences of the locus coeruleus on migraine pathophysiology. Pain. 2019;160(2):385–94. https://doi.org/10.1097/j.pain.0000000000001421</mixed-citation><mixed-citation xml:lang="en">Vila-Pueyo M, Strother LC, Kefel M, Goadsby PJ, Holland PR. Divergent influences of the locus coeruleus on migraine pathophysiology. Pain. 2019;160(2):385–94. https://doi.org/10.1097/j.pain.0000000000001421</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Sokolov AY, Lyubashina OA, Panteleev SS. The role of noradrenalin in the pathogenesis of primary headaches. Neurochemical Journal. 2013;7(4):251–6. https://doi.org/10.1134/S1819712413040090</mixed-citation><mixed-citation xml:lang="en">Sokolov AY, Lyubashina OA, Panteleev SS. The role of noradrenalin in the pathogenesis of primary headaches. Neurochemical Journal. 2013;7(4):251–6. https://doi.org/10.1134/S1819712413040090</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Frederiksen SD, Bekker-Nielsen Dunbar M, Snoer AH, Deen M, Edvinsson L. 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. 2020;60(6):1132–64. https://doi.org/10.1111/head.13802</mixed-citation><mixed-citation xml:lang="en">Frederiksen SD, Bekker-Nielsen Dunbar M, Snoer AH, Deen M, Edvinsson L. 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. 2020;60(6):1132–64. https://doi.org/10.1111/head.13802</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">D’Andrea G, D’Arrigo A, Bussone G, Bolner A, Aguggia M, Saracco MG, et al. Tryptamine levels are low in plasma of chronic migraine and chronic tension-type headache. Neurological Sciences. 2014;35(12):1941–5. https://doi.org/10.1007/s10072-014-1867-5</mixed-citation><mixed-citation xml:lang="en">D’Andrea G, D’Arrigo A, Bussone G, Bolner A, Aguggia M, Saracco MG, et al. Tryptamine levels are low in plasma of chronic migraine and chronic tension-type headache. Neurological Sciences. 2014;35(12):1941–5. https://doi.org/10.1007/s10072-014-1867-5</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Wang Y, Jing X, Lv K, Wu B, Bai Y, Luo Y, et al. During the long way to Mars: effects of 520 days of confinement (Mars500) on the assessment of affective stimuli and stage alteration in mood and plasma hormone levels. PLoS One. 2014;9(4):e87087. https://doi.org/10.1371/journal.pone.0087087</mixed-citation><mixed-citation xml:lang="en">Wang Y, Jing X, Lv K, Wu B, Bai Y, Luo Y, et al. During the long way to Mars: effects of 520 days of confinement (Mars500) on the assessment of affective stimuli and stage alteration in mood and plasma hormone levels. PLoS One. 2014;9(4):e87087. https://doi.org/10.1371/journal.pone.0087087</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Tajti J, Szok D, Majláth Z, Tuka B, Csati A, Vescei L. Migraine and neuropeptides. Neuropeptides. 2015;52:19–30. https://doi.org/10.1016/j.npep.2015.03.006</mixed-citation><mixed-citation xml:lang="en">Tajti J, Szok D, Majláth Z, Tuka B, Csati A, Vescei L. Migraine and neuropeptides. Neuropeptides. 2015;52:19–30. https://doi.org/10.1016/j.npep.2015.03.006</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Ramachandran R. Neurogenic inflammation and its role in migraine. Seminars in Immunopathology. 2018;40(3):301–14. https://doi.org/10.1007/s00281-018-0676-y</mixed-citation><mixed-citation xml:lang="en">Ramachandran R. Neurogenic inflammation and its role in migraine. Seminars in Immunopathology. 2018;40(3):301–14. https://doi.org/10.1007/s00281-018-0676-y</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Lassen LH, Jacobsen VB, Haderslev PA, Sperling B, Iversen HK, Olesen J, et al. Involvement of calcitonin generelated peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. The Journal of Headache and Pain. 2008;9(3):151–7. https://doi.org/10.1007/s10194-008-0036-2</mixed-citation><mixed-citation xml:lang="en">Lassen LH, Jacobsen VB, Haderslev PA, Sperling B, Iversen HK, Olesen J, et al. Involvement of calcitonin generelated peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. The Journal of Headache and Pain. 2008;9(3):151–7. https://doi.org/10.1007/s10194-008-0036-2</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Edvinsson L, Warfvinge K. Recognizing the role of CGRP and CGRP receptors in migraine and its treatment. Cephalalgia. 2019;39(3):366–73. https://doi.org/10.1177/0333102418801592</mixed-citation><mixed-citation xml:lang="en">Edvinsson L, Warfvinge K. Recognizing the role of CGRP and CGRP receptors in migraine and its treatment. Cephalalgia. 2019;39(3):366–73. https://doi.org/10.1177/0333102418801592</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Alpay B, Christensen RH, Al-Khazali HM, Ashina M, Ashina H. Substance P and the trigeminovascular system: from preclinical mechanisms to human headache induction. Cephalalgia. 2025;45(8):3331024251355944. https://doi.org/10.1177/03331024251355944</mixed-citation><mixed-citation xml:lang="en">Alpay B, Christensen RH, Al-Khazali HM, Ashina M, Ashina H. Substance P and the trigeminovascular system: from preclinical mechanisms to human headache induction. Cephalalgia. 2025;45(8):3331024251355944. https://doi.org/10.1177/03331024251355944</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Scher AI, McGinley JS, VanDam LR, Campbell AM, Chai X, Collins B, et al. Plasma calcitonin gene-related peptide and nerve growth factor as headache and pain biomarkers in recently deployed soldiers with and without a recent concussion. Headache. 2023;63(10):1360–70. https://doi.org/10.1111/head.14635</mixed-citation><mixed-citation xml:lang="en">Scher AI, McGinley JS, VanDam LR, Campbell AM, Chai X, Collins B, et al. Plasma calcitonin gene-related peptide and nerve growth factor as headache and pain biomarkers in recently deployed soldiers with and without a recent concussion. Headache. 2023;63(10):1360–70. https://doi.org/10.1111/head.14635</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
