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<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Regional Anesthesia and Acute Pain Management</journal-id><journal-title-group><journal-title xml:lang="en">Regional Anesthesia and Acute Pain Management</journal-title><trans-title-group xml:lang="ru"><trans-title>Регионарная анестезия и лечение острой боли</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1993-6508</issn><issn publication-format="electronic">2687-1394</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">695450</article-id><article-id pub-id-type="doi">10.17816/RA695450</article-id><article-id pub-id-type="edn">MIAMOX</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original study articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные исследования</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Analgesic efficacy of krypton-oxygen gas mixture inhalation in a rat model of neuropathic pain</article-title><trans-title-group xml:lang="ru"><trans-title>Эффективность ингаляций криптон-кислородной газовой смеси на модели нейропатического типа болевого синдрома</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0009-2965-233X</contrib-id><name-alternatives><name xml:lang="en"><surname>Loboda</surname><given-names>Anton V.</given-names></name><name xml:lang="ru"><surname>Лобода</surname><given-names>Антон Васильевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>a.loboda@ingasgroup.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0005-7574-5685</contrib-id><name-alternatives><name xml:lang="en"><surname>Panasenkov</surname><given-names>Pavel D.</given-names></name><name xml:lang="ru"><surname>Панасенков</surname><given-names>Павел Дмитриевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>p.panasenkov@ingasgroup.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0514-2177</contrib-id><contrib-id contrib-id-type="spin">1467-7499</contrib-id><name-alternatives><name xml:lang="en"><surname>Cherpakov</surname><given-names>Rostislav A.</given-names></name><name xml:lang="ru"><surname>Черпаков</surname><given-names>Ростислав Александрович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>Zealot333@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0819-7886</contrib-id><contrib-id contrib-id-type="spin">7843-4176</contrib-id><name-alternatives><name xml:lang="en"><surname>Antonova</surname><given-names>Viktoriya V.</given-names></name><name xml:lang="ru"><surname>Антонова</surname><given-names>Виктория Витальевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>vantonova@fnkcrr.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0006-9976-1134</contrib-id><name-alternatives><name xml:lang="en"><surname>Potapov</surname><given-names>Sergey V.</given-names></name><name xml:lang="ru"><surname>Потапов</surname><given-names>Сергей Владимирович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Engineering)</p></bio><bio xml:lang="ru"><p>канд. техн. наук</p></bio><email>s.potapov@ingasgroup.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">InertGaz Medical</institution></aff><aff><institution xml:lang="ru">ИнертГаз Медикал</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology</institution></aff><aff><institution xml:lang="ru">Федеральный научно-клинический центр реаниматологии и реабилитологии</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2026-02-25" publication-format="electronic"><day>25</day><month>02</month><year>2026</year></pub-date><pub-date date-type="pub" iso-8601-date="2026-05-09" publication-format="electronic"><day>09</day><month>05</month><year>2026</year></pub-date><volume>20</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>16</fpage><lpage>24</lpage><history><date date-type="received" iso-8601-date="2025-10-29"><day>29</day><month>10</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2026-02-16"><day>16</day><month>02</month><year>2026</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, Эко-Вектор</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://eco-vector.com/for_authors.php#07</ali:license_ref></license></permissions><self-uri xlink:href="https://rjraap.com/1993-6508/article/view/695450">https://rjraap.com/1993-6508/article/view/695450</self-uri><abstract xml:lang="en"><p><bold>BACKGROUND:</bold> Neuropathic pain is one of the most challenging forms of chronic pain and is often refractory to standard pharmacotherapy. Given the limited efficacy of existing therapies, inert gases have attracted interest as potential modulators of nociceptive signaling.</p> <p><bold>AIM:</bold> This work aimed to evaluate the analgesic activity of a krypton-oxygen gas mixture (KrypOx 79) in a preclinical rat model of neuropathic pain.</p> <p><bold>METHODS:</bold> The experiment was conducted in male Wistar rats (n = 40). Neuropathic pain was induced using the chronic constriction injury (CCI) model of the sciatic nerve (Bennett and Xie). Animals were randomly assigned to three groups: krypton–oxygen gas mixture 79 (<italic>n</italic> = 8), control (air mixture, <italic>n</italic> = 8), and gabapentin 372 mg/kg (<italic>n</italic> = 8). Analgesic effects were assessed by changes in mechanical sensitivity thresholds using von Frey filaments (Dixon–Chaplan method) on day 14 after model induction. Statistical analysis was performed using nonparametric tests (Kruskal–Wallis, Friedman test, Dunn post hoc correction).</p> <p><bold>RESULTS:</bold> Rats in the KrypOx 79 group demonstrated a significant 3–4–fold increase in mechanical sensitivity thresholds compared with baseline at 0 and 30 minutes after inhalation (<italic>p</italic> &lt; 0.05). The analgesic effect gradually declined within 3–4 hours. In the gabapentin group, reduced sensitivity was observed at 3–4 hours after administration, which is consistent with its pharmacokinetic profile.</p> <p><bold>CONCLUSION:</bold> The krypton–oxygen gas mixture (KrypOx 79) produces a pronounced but short-lived analgesic effect in a model of neuropathic pain, with onset within the first 30 minutes after exposure. These findings support the potential of krypton as a fast-acting inhalational analgesic and justify further studies to investigate its mechanisms of action and possible clinical applications.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Обоснование.</bold> Нейропатическая боль является одной из наиболее сложных форм хронического болевого синдрома и плохо поддаётся стандартной фармакотерапии. В условиях ограниченной эффективности существующих средств особый интерес вызывают инертные газы как потенциальные модуляторы болевого импульса.</p> <p><bold>Цель.</bold> Оценить анальгетическую активность криптон-кислородной газовой смеси (КрипОкс 79) в доклинической модели нейропатического болевого синдрома у крыс.</p> <p><bold>Методы.</bold> Эксперимент выполнен на самцах крыс линии Wistar (<italic>n=</italic>40). Нейропатическая боль моделировалась методом хронического сдавления седалищного нерва (CCI — Chronic Constriction Injury по Bennett и Xie). Животные были случайным образом распределены на три группы: КрипОкс 79 (<italic>n=</italic>8), Контроль (воздушная смесь, <italic>n=</italic>8), Габапентин в дозе 372 мг/кг (<italic>n=</italic>8). Анальгетический эффект оценивали по изменению порогов тактильной чувствительности (нити фон Фрея, метод Dixon–Chaplan) на 14-й день после моделирования. Статистическую обработку проводили с использованием непараметрических критериев (Краскела–Уоллиса, Фридмана, поправка Данна).</p> <p><bold>Результаты.</bold> У крыс группы КрипОкс 79 отмечено значимое повышение порогов тактильной чувствительности в 3–4 раза по сравнению с исходным уровнем на точках 0 и 30 минут после ингаляции (<italic>p &lt;</italic>0,05). Анальгетический эффект постепенно снижался к 3–4 часам. В группе габапентина снижение чувствительности наблюдалось через 3–4 часа после введения, что соответствует его фармакокинетическому профилю.</p> <p><bold>Заключение.</bold> Криптон-кислородная смесь (КрипОкс 79) оказывает выраженное, но кратковременное анальгетическое действие в модели нейропатической боли, проявляющееся в первые 30 минут после экспозиции. Полученные данные подтверждают перспективность криптона как быстродействующего ингаляционного анальгетика и обосновывают необходимость дальнейших исследований по изучению его механизмов и возможного клинического применения.</p></trans-abstract><kwd-group xml:lang="en"><kwd>neuropathic pain</kwd><kwd>krypton</kwd><kwd>inert gases</kwd><kwd>sciatic nerve constriction</kwd><kwd>rats</kwd><kwd>analgesia</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>нейропатическая боль</kwd><kwd>криптон</kwd><kwd>инертные газы</kwd><kwd>сдавление седалищного нерва</kwd><kwd>крысы</kwd><kwd>аналгезия</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Raja SN, Carr DB, Cohen M, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161(9):1976–1982. doi: 10.1097/j.pain.0000000000001939</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52(1):77–92. doi: 10.1016/j.neuron.2006.09.021</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology and its clinical relevance. Br J Anaesth. 2013;111(1):13–18. doi: 10.1093/bja/aet123</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 2008;136(3):380–387. doi: 10.1016/j.pain.2007.08.013</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep. 2012;16(3):191–198. doi: 10.1007/s11916-012-0256-0 EDN: GIPJOG</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Baskozos G, Hébert HL, Pascal MM, et al. Epidemiology of neuropathic pain: an analysis of prevalence and associated factors in UK Biobank. Pain Rep. 2023;8(2):e1066. doi: 10.1097/PR9.0000000000001066 EDN: AFHSTM</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006;7(4):281–289. doi: 10.1016/j.jpain.2005.11.008</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Moisset X. Neuropathic pain: Evidence based recommendations. Presse Med. 2024;53(2):104232. doi: 10.1016/j.lpm.2024.104232 EDN: VXNZFW</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173. doi: 10.1016/S1474-4422(14)70251-0</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6(6):CD007938. doi: 10.1002/14651858.CD007938.pub4</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Meaadi J, Obara I, Eldabe S, Nazar H. The safety and efficacy of gabapentinoids in the management of neuropathic pain: a systematic review with meta-analysis of randomised controlled trials. Int J Clin Pharm. 2023;45(3):556–565. doi: 10.1007/s11096-022-01528-y EDN: BIXPKT</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Sadegh AA, Gehr NL, Finnerup NB. A systematic review and meta-analysis of randomized controlled head-to-head trials of recommended drugs for neuropathic pain. Pain Rep. 2024;9(2):e1138. doi: 10.1097/PR9.0000000000001138 EDN: RUQAQU</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33(1):87–107. doi: 10.1016/0304-3959(88)90209-6</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain. 1990;43(2):205–218. doi: 10.1016/0304-3959(90)91074-S</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Wrathall JR, Pettegrew RK, Harvey F. Spinal cord contusion in the rat: production of graded, reproducible, injury groups. Exp Neurol. 1985;88(1):108–122. doi: 10.1016/0014-4886(85)90117-7</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Courteix C, Eschalier A, Lavarenne J. Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain. Pain. 1993;53(1):81–88. doi: 10.1016/0304-3959(93)90059-X</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53(1):55–63. doi: 10.1016/0165-0270(94)90144-9</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Franks NP, Dickinson R, de Sousa SL, Hall AC, Lieb WR. How does xenon produce anaesthesia? Nature. 1998;396(6709):324. doi: 10.1038/24525</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Petersen-Felix S, Luginbühl M, Schnider TW, et al. Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain. Br J Anaesth. 1998;81(5):742–747. doi: 10.1093/bja/81.5.742 EDN: IMIZIN</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Dickinson R, Franks NP. Bench-to-bedside review: Molecular pharmacology and clinical use of inert gases in anesthesia and neuroprotection. Crit Care. 2010;14(4):229. doi: 10.1186/cc9051 EDN: PKXVIH</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Junck L, Dhawan V, Thaler HT, Rottenberg DA. Effects of xenon and krypton on regional cerebral blood flow in the rat. J Cereb Blood Flow Metab. 1985;5(1):126–132. doi: 10.1038/jcbfm.1985.16</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Melnikov I, Orekhov P, Rulev M, et al. High-pressure crystallography shows noble gas intervention into protein-lipid interaction and suggests a model for anaesthetic action. Commun Biol. 2022;5(1):360. doi: 10.1038/s42003-022-03233-y</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Yin H, Chen Z, Zhao H, Huang H, Liu W. Noble gas and neuroprotection: From bench to bedside. Front Pharmacol. 2022;13:1028688. doi: 10.3389/fphar.2022.1028688 EDN: NOFJEV</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Antonova VV, Shumov IV, Dolgikh VT, et al. Influence of breathing krypton-oxygen mixture on signalling cascades in the rat brain in the simulation of photoinduced ischemic stroke. Bulletin of Experimental Biology and Medicine. 2024;178(9):321–327. doi: 10.47056/0365-9615-2024-178-9-321-327 EDN: LCDOJS</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Shumov IV, Antonova VV, Boeva EA, Dolgikh VT, Grebenchikov OA. Neuroprotective properties of krypton in photo-induced cerebral infarction in rats. Vestnik SurGU. Meditsina. 2023;16(3):89–96. doi: 10.35266/2304-9448-2023-3-89-96 EDN: HXZWIS</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union. 2010;L276:33–79.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, DC: National Academies Press; 2011. doi: 10.17226/12910</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Dixon WJ. The up-and-down method for small samples. Journal of the American Statistical Association. 1965;60(312):967–978. doi: 10.1080/01621459.1965.10480843</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Antonova VV, Silachev DN, Plotnikov EY, et al. Neuroprotective Effects of Krypton Inhalation on Photothrombotic Ischemic Stroke. Biomedicines. 2024;12(3):635. doi: 10.3390/biomedicines12030635 EDN: NPKZRV</mixed-citation></ref></ref-list></back></article>
