<?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">r-n-j</journal-id><journal-title-group><journal-title xml:lang="ru">Российский неврологический журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Russian neurological journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2658-7947</issn><issn pub-type="epub">2686-7192</issn><publisher><publisher-name>МИА</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30629/2658-7947-2022-27-5-51-58</article-id><article-id custom-type="elpub" pub-id-type="custom">r-n-j-360</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>ИССЛЕДОВАНИЯ И КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>CLINICAL RESEARCHES AND CASE REPORTS</subject></subj-group></article-categories><title-group><article-title>Показатели системы цитокинов и неоангиогенеза в крови при острой дискогенной пояснично-крестцовой радикулопатии у пациентов молодого возраста</article-title><trans-title-group xml:lang="en"><trans-title>Cytokines and neoangiogenesis parameters in young patients with acute discogenic lumbosacral radiculopathy</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7682-6672</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Максимова</surname><given-names>М Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Maksimova</surname><given-names>M. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Москва </p></bio><bio xml:lang="en"><p> Moscow </p></bio><email xlink:type="simple">ncnmaximova@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/0000-0002-6756-5511</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Котляр</surname><given-names>Я. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kotlyar</surname><given-names>Y. А.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Москва </p><p> </p></bio><bio xml:lang="en"><p> Moscow </p></bio><email xlink:type="simple">doctor_kot12@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/0000-0001-9604-7775</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шабалина</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shabalina</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p> Москва </p><p> </p></bio><bio xml:lang="en"><p> Moscow </p></bio><email xlink:type="simple">ashabalina@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научный центр неврологии»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Center of Neurology</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>24</day><month>11</month><year>2022</year></pub-date><volume>27</volume><issue>5</issue><fpage>51</fpage><lpage>58</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Максимова М.Ю., Котляр Я.А., Шабалина А.А., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Максимова М.Ю., Котляр Я.А., Шабалина А.А.</copyright-holder><copyright-holder xml:lang="en">Maksimova M.Y., Kotlyar Y.А., Shabalina A.A.</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.r-n-j.com/jour/article/view/360">https://www.r-n-j.com/jour/article/view/360</self-uri><abstract><sec><title>Введение</title><p>Введение. Патогенез дискогенной пояснично-крестцовой боли у лиц молодого возраста является сложным и многокомпонентным. Данные по содержанию цитокинов и факторов неоангиогенеза при острой дискогенной пояснично-крестцовой радикулопатии немногочисленны и зачастую противоречивы.</p></sec><sec><title>Цель исследования</title><p>Цель исследования: оценить показатели системы цитокинов и неоангиогенеза в крови при острой дискогенной пояснично-крестцовой радикулопатии у пациентов молодого возраста.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. В исследовании приняли участие 49 пациентов (27 (55,1%) мужчин и 22 (44,9%) женщины) в возрасте 36 [27; 45] лет с острой пояснично-крестцовой болью, обусловленной дегенеративными изменениями позвоночника и компрессией спинномозговых нервов по данным МРТ. Группу контроля составили 17 здоровых лиц (10 (58,8%) мужчин и 7 (41,2%) женщин) в возрасте 33 [25; 41] лет. Уровень C-реактивного белка измеряли на автоматическом биохимическом анализаторе Konelab 30Iprime (ThermoFisher, Финляндия). Уровни интерлейкина-1β (ИЛ-1β), интерлейкина-6 (ИЛ-6), интерлейкина-8 (ИЛ-8), фактора некроза опухоли альфа (ФНО-α), фактора роста эндотелия cосудов А (ФРЭС-А) в крови определяли твердофазным иммуноферментным методом (ELISA) на плашечном ИФА-анализаторе Реал-бест (Россия) с использованием наборов реагентов Cloud-Clone Corp. (США, Китай).</p></sec><sec><title>Результаты</title><p>Результаты. У пациентов молодого возраста с острой дискогенной пояснично-крестцовой радикулопатией по сравнению с контрольной группой выявлено повышение уровней С-реактивного белка (11,2 [7,1; 15,3] против 4,2 [3,5; 4,9] мг/мл; р = 0,011), ФНО-α (23,1 [16,8; 29,5] против 9,7 [6,9; 12,5] пг/мл; р = 0,001), ИЛ-1β (4,7 [3,1; 6,3] против 3,2 [2,3;4,1] пг/мл; р = 0,041), ИЛ-6 (11,2 [6,1; 16,3] против 4,5 [3,1; 5,9] пг/мл; р = 0,007), ИЛ-8 (30,3 [21,9; 48,8] против 20,5 [8,5; 32,6] пг/мл; р = 0,023) и ФРЭС-А (318 [260; 570] против 168 [100; 240] пг/мл; р = 0,002).</p></sec><sec><title>Заключение</title><p>Заключение. Полученные результаты подтверждают значение провоспалительных факторов и показателей неоангиогенеза в развитии острой дискогенной пояснично-крестцовой радикулопатии у пациентов молодого возраста.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Discogenic lumbosacral pain in young people has a complex and multicomponent pathogenesis. Evidence of the content of cytokines and neoangiogenesis factors in patients with acute discogenic lumbosacral radiculopathy are deficiency and often contradictory. Objective: to evaluate the cytokine and neoangiogenesis parameters in the blood of young patients with acute discogenic lumbosacral radiculopathy.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. The study involved 49 patients (27 (55.1%) men and 22 (44.9%) women) with a mean age of 36 [27; 45] years with acute lumbosacral pain caused by degenerative changes in the spine and signs of compression of the spinal nerves, according to MRI. The control group consisted of 17 healthy individuals (10 (58.8%) men and 7 (41.2%) women) with a mean age of 33 [25; 41] years. The level of C-reactive protein was measured by an automatic biochemical analyzer Konelab 30Iprime (ThermoFisher, Finland). The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor A (VEGF-A) in blood were determined by enzyme-linked immunosorbent assay (ELISA) on a plate ELISA analyzer Real-best (Russia) using reagent kits Cloud-Clone Corp. (USA, China).</p></sec><sec><title>Results</title><p>Results. Patients with acute discogenic lumbosacral radiculopathy, compared with the control group, has an increase in the levels of C-reactive protein (11.2 [7.1; 15.3] vs. 4.2 [3.5; 4.9] mg/ml; р = 0.011), TNF-α (23.1 [16.8; 29.5] vs. 9.7 [6.9; 12,5] pg/ml; р = 0.001), IL-1β (4.7 [3.1; 6.3] vs. 3.2 [2.3; 4.1] pg/ml; р = 0.041), IL-6 (11.2 [6.1; 16.3] vs. 4.5 [3.1; 5.9] pg/ml; р = 0.007), IL-8 (30. [21.9; 48.8] vs. 20.5 [8.5; 32.6] pg/ml; р = 0.023) and VEGF-A (318 [260; 570] vs.168 [100; 240] pg/ml; р = 0.002).</p></sec><sec><title>Conclusion</title><p>Conclusion. The obtained results confirm the importance of pro-inflammatory factors and indicators of neoangiogenesis in the development of acute discogenic lumbosacral radiculopathy in young patients.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>острая дискогенная пояснично-крестцовая радикулопатия</kwd><kwd>цитокины</kwd><kwd>фактор роста эндотелия сосудов А</kwd></kwd-group><kwd-group xml:lang="en"><kwd>acute discogenic lumbosacral radiculopathy</kwd><kwd>cytokines</kwd><kwd>vascular endothelial growth factor A</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Парфенов В.А., Яхно Н.Н., Давыдов О.С., Кукушкин М.Л., Чурюканов М.В., Головачева В.А., и др. Дискогенная пояснично-крестцовая радикулопатия. Рекомендации Российского общества по изучению боли (РОИБ). Неврология, нейропсихиатрия, психосоматика. 2020;12(4):15–24. [Parfenov V.A., Yakhno N.N., Davydov O.S., Kukushkin M.L., Churyukanov M.V., Golovacheva V.A. et al. Discogenic lumbosacral radiculopathy. Recommendations of the Russian Association for the Study of Pain (RSSP). Neurology, Neuropsychiatry, Psychosomatics. 2020;12(4):15–24. (In Russ.)]. https://doi.org/10.14412/2074-2711-2020-4-15-24</mixed-citation><mixed-citation xml:lang="en">Парфенов В.А., Яхно Н.Н., Давыдов О.С., Кукушкин М.Л., Чурюканов М.В., Головачева В.А., и др. Дискогенная пояснично-крестцовая радикулопатия. Рекомендации Российского общества по изучению боли (РОИБ). Неврология, нейропсихиатрия, психосоматика. 2020;12(4):15–24. [Parfenov V.A., Yakhno N.N., Davydov O.S., Kukushkin M.L., Churyukanov M.V., Golovacheva V.A. et al. Discogenic lumbosacral radiculopathy. Recommendations of the Russian Association for the Study of Pain (RSSP). Neurology, Neuropsychiatry, Psychosomatics. 2020;12(4):15–24. (In Russ.)]. https://doi.org/10.14412/2074-2711-2020-4-15-24</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Konstantinou K., Dunn K.M. Sciatica: review of epidemiological studies and prevalence estimates. Spine (Phila Pa 1976). 2008;33(22):2464–72. https://doi.org/10.1097/BRS.0b013e318183a4a2</mixed-citation><mixed-citation xml:lang="en">Konstantinou K., Dunn K.M. Sciatica: review of epidemiological studies and prevalence estimates. Spine (Phila Pa 1976). 2008;33(22):2464–72. https://doi.org/10.1097/BRS.0b013e318183a4a2</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Bardin L.D., King P., Maher C.G. Diagnostic triage for low back pain: a practical approach for primary care. Med J Aust. 2017;206(6):268–73. https://doi.org/10.5694/mja16.00828</mixed-citation><mixed-citation xml:lang="en">Bardin L.D., King P., Maher C.G. Diagnostic triage for low back pain: a practical approach for primary care. Med J Aust. 2017;206(6):268–73. https://doi.org/10.5694/mja16.00828</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Battié M.C., Joshi A.B., Gibbons L.E.; ISSLS Degenerative Disc Disease: What is in a Name? Degenerative Spinal Phenotypes Group. Spine (Phila Pa 1976). 2019;44(21):1523–1529. https://doi.org/10.1097/BRS.0000000000003103</mixed-citation><mixed-citation xml:lang="en">Battié M.C., Joshi A.B., Gibbons L.E.; ISSLS Degenerative Disc Disease: What is in a Name? Degenerative Spinal Phenotypes Group. Spine (Phila Pa 1976). 2019;44(21):1523–1529. https://doi.org/10.1097/BRS.0000000000003103</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Urits I., Burshtein A., Sharma M., Testa L., Gold P.A., Orhurhu V. et al. Low Back Pain, a Comprehensive Review: Pathophysiology, Diagnosis, and Treatment. Curr Pain Headache Rep. 2019;23(3):23. https://doi.org/10.1007/s11916-019-0757-1</mixed-citation><mixed-citation xml:lang="en">Urits I., Burshtein A., Sharma M., Testa L., Gold P.A., Orhurhu V. et al. Low Back Pain, a Comprehensive Review: Pathophysiology, Diagnosis, and Treatment. Curr Pain Headache Rep. 2019;23(3):23. https://doi.org/10.1007/s11916-019-0757-1</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Hayes A.J., Benjamin M., Ralphs J.R. Extracellular matrix in development of the intervertebral disc. Matrix Biol. 2001;20(2):107–121. https://doi.org/10.1016/s0945-053x(01)00125-1</mixed-citation><mixed-citation xml:lang="en">Hayes A.J., Benjamin M., Ralphs J.R. Extracellular matrix in development of the intervertebral disc. Matrix Biol. 2001;20(2):107–121. https://doi.org/10.1016/s0945-053x(01)00125-1</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Hutton W.C., Ganey T.M., Elmer W.A., Kozlowska E., Ugbo J.L., Doh E.S., Whitesides T.E. Jr. Does long-term compressive loading on the intervertebral disc cause degeneration? Spine (Phila Pa 1976). 2000;25(23):2993–3004. https://doi.org/10.1097/00007632-200012010-00006</mixed-citation><mixed-citation xml:lang="en">Hutton W.C., Ganey T.M., Elmer W.A., Kozlowska E., Ugbo J.L., Doh E.S., Whitesides T.E. Jr. Does long-term compressive loading on the intervertebral disc cause degeneration? Spine (Phila Pa 1976). 2000;25(23):2993–3004. https://doi.org/10.1097/00007632-200012010-00006</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Urban J.P., Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther. 2003;5(3):120–130. https://doi.org/10.1186/ar629</mixed-citation><mixed-citation xml:lang="en">Urban J.P., Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther. 2003;5(3):120–130. https://doi.org/10.1186/ar629</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Roughley P.J., Alini M., Antoniou J. The role of proteoglycans in aging, degeneration and repair of the intervertebral disc. Biochem Soc Trans. 2002;30(Pt6):869–874. https://doi.org/10.1042/bst0300869</mixed-citation><mixed-citation xml:lang="en">Roughley P.J., Alini M., Antoniou J. The role of proteoglycans in aging, degeneration and repair of the intervertebral disc. Biochem Soc Trans. 2002;30(Pt6):869–874. https://doi.org/10.1042/bst0300869</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Khan A.N., Jacobsen H.E., Khan J., Filippi C.G., Levine M., Lehman R.A. Jr. et al. Inflammatory biomarkers.of.low back pain and disc degeneration: a review. Ann N Y Acad Sci. 2017;1410(1):68–84. https://doi.org/10.1111/nyas.13551</mixed-citation><mixed-citation xml:lang="en">Khan A.N., Jacobsen H.E., Khan J., Filippi C.G., Levine M., Lehman R.A. Jr. et al. Inflammatory biomarkers.of.low back pain and disc degeneration: a review. Ann N Y Acad Sci. 2017;1410(1):68–84. https://doi.org/10.1111/nyas.13551</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Li W., Gong Y., Liu .J, Guo Y., Tang H., Qin S. et al. Peripheral and Central Pathological Mechanisms of Chronic Low Back Pain: A Narrative Review. J Pain Res. 2021;14:1483–1494. https://doi.org/10.2147/JPR.S306280</mixed-citation><mixed-citation xml:lang="en">Li W., Gong Y., Liu .J, Guo Y., Tang H., Qin S. et al. Peripheral and Central Pathological Mechanisms of Chronic Low Back Pain: A Narrative Review. J Pain Res. 2021;14:1483–1494. https://doi.org/10.2147/JPR.S306280</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Raj P.P. Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract. 2008;8(1):18–44. https://doi.org/10.1111/j.1533-2500.2007.00171.x</mixed-citation><mixed-citation xml:lang="en">Raj P.P. Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract. 2008;8(1):18–44. https://doi.org/10.1111/j.1533-2500.2007.00171.x</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Ohtori S., Inoue G., Miyagi M., Takahashi K. Pathomechanisms of discogenic low back pain in humans and animal models. Spine J. 2015;15(6):1347–1355. https://doi.org/10.1016/j.spinee.2013.07.490</mixed-citation><mixed-citation xml:lang="en">Ohtori S., Inoue G., Miyagi M., Takahashi K. Pathomechanisms of discogenic low back pain in humans and animal models. Spine J. 2015;15(6):1347–1355. https://doi.org/10.1016/j.spinee.2013.07.490</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Pfirrmann C.W., Dora C., Schmid M.R., Zanetti M., Hodler J., Boos N. MR image-based grading of lumbar nerve root compromise due to disk herniation: reliability study with surgical correlation. Radiology. 2004;230(2):583–8. https://doi.org/10.1148/radiol.2302021289</mixed-citation><mixed-citation xml:lang="en">Pfirrmann C.W., Dora C., Schmid M.R., Zanetti M., Hodler J., Boos N. MR image-based grading of lumbar nerve root compromise due to disk herniation: reliability study with surgical correlation. Radiology. 2004;230(2):583–8. https://doi.org/10.1148/radiol.2302021289</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Walsh J., Rabey M.I., Hall T.M. Agreement and correlation between the self-report leeds assessment of neuropathic symptoms and signs and DouleurNeuropathique 4 Questions neuropathicpain screening tools in subjects with low back-related leg pain. J Manipulative Physiol Ther. 2012;35(3):196–202. https://doi.org/10.1016/j.jmpt.2012.02.001</mixed-citation><mixed-citation xml:lang="en">Walsh J., Rabey M.I., Hall T.M. Agreement and correlation between the self-report leeds assessment of neuropathic symptoms and signs and DouleurNeuropathique 4 Questions neuropathicpain screening tools in subjects with low back-related leg pain. J Manipulative Physiol Ther. 2012;35(3):196–202. https://doi.org/10.1016/j.jmpt.2012.02.001</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Freynhagen R., Baron R., Gockel U., Tölle T.R. painDETECT: a newscreening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006;22(10):1911–20. https://doi.org/10.1185/030079906X132488</mixed-citation><mixed-citation xml:lang="en">Freynhagen R., Baron R., Gockel U., Tölle T.R. painDETECT: a newscreening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006;22(10):1911–20. https://doi.org/10.1185/030079906X132488</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Sun Z., Zhang M., Zhao X.H., Liu Z.H., Gao Y., Samartzis D. et al. Immune cascades in human intervertebral disc: the pros and cons. Int J Clin Exp Pathol. 2013;6(6):1009–14. Print 2013. PMID: 23696917.</mixed-citation><mixed-citation xml:lang="en">Sun Z., Zhang M., Zhao X.H., Liu Z.H., Gao Y., Samartzis D. et al. Immune cascades in human intervertebral disc: the pros and cons. Int J Clin Exp Pathol. 2013;6(6):1009–14. Print 2013. PMID: 23696917.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Yoshida M., Nakamura T., Sei A., Kikuchi T., Takagi K., Matsukawa A. Intervertebral disc cells produce tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model. Spine. 2005;30(1):55–61. https://doi.org/10.1097/01.brs.0000149194.17891.bf</mixed-citation><mixed-citation xml:lang="en">Yoshida M., Nakamura T., Sei A., Kikuchi T., Takagi K., Matsukawa A. Intervertebral disc cells produce tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model. Spine. 2005;30(1):55–61. https://doi.org/10.1097/01.brs.0000149194.17891.bf</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Takada T., Nishida K., Doita M., Miyamoto H., Kurosaka M. Interleukin-6 production is upregulated by interaction between disc tissue and macrophages. Spine. 2004;29(10):1089–1092; discussion 1093. https://doi.org/10.1097/00007632-200405150-00007</mixed-citation><mixed-citation xml:lang="en">Takada T., Nishida K., Doita M., Miyamoto H., Kurosaka M. Interleukin-6 production is upregulated by interaction between disc tissue and macrophages. Spine. 2004;29(10):1089–1092; discussion 1093. https://doi.org/10.1097/00007632-200405150-00007</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Lim Y.Z., Wang Y., Cicuttini F.M., Hughes H.J., Chou L., Urquhart D.M. et al. Association Between Inflammatory Biomarkers and Nonspecific Low Back Pain: A Systematic Review. Clin J Pain. 2020;36(5):379–389. https://doi.org/10.1097/AJP.0000000000000810</mixed-citation><mixed-citation xml:lang="en">Lim Y.Z., Wang Y., Cicuttini F.M., Hughes H.J., Chou L., Urquhart D.M. et al. Association Between Inflammatory Biomarkers and Nonspecific Low Back Pain: A Systematic Review. Clin J Pain. 2020;36(5):379–389. https://doi.org/10.1097/AJP.0000000000000810</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Kushner I., Jiang S.L., Zhang D.X., Lozanski G., Samols D. Do post-transcriptional mechanisms participate in induction of C-reactive protein and serum amyloid A by IL-6 and IL-1? Interleukin-6 Type Cytokines. 1995;762:102–107. https://doi.org/10.1111/j.1749-6632.1995.tb32318.x</mixed-citation><mixed-citation xml:lang="en">Kushner I., Jiang S.L., Zhang D.X., Lozanski G., Samols D. Do post-transcriptional mechanisms participate in induction of C-reactive protein and serum amyloid A by IL-6 and IL-1? Interleukin-6 Type Cytokines. 1995;762:102–107. https://doi.org/10.1111/j.1749-6632.1995.tb32318.x</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Sproston N.R., Ashworth J.J. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754</mixed-citation><mixed-citation xml:lang="en">Sproston N.R., Ashworth J.J. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Le Gars L., Borderie D., Kaplan G., Berenbaum F. Systemic inflammatory response with plasma C-reactive protein elevation in disk-related lumbosciatic syndrome. Joint Bone Spine. 2000;67(5):452–5. PMID: 11143913</mixed-citation><mixed-citation xml:lang="en">Le Gars L., Borderie D., Kaplan G., Berenbaum F. Systemic inflammatory response with plasma C-reactive protein elevation in disk-related lumbosciatic syndrome. Joint Bone Spine. 2000;67(5):452–5. PMID: 11143913</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Gebhardt K., Brenner H., Stürmer T. et al. The course of high-sensitive C-reactive protein in correlation with pain and clinical function in patients with acute lumbosciatic pain and chronic low back pain — a 6 months prospective longitudinal study. Eur J Pain. 2006;10(8):711–9. https://doi.org/10.1016/j.ejpain.2005.11.005</mixed-citation><mixed-citation xml:lang="en">Gebhardt K., Brenner H., Stürmer T. et al. The course of high-sensitive C-reactive protein in correlation with pain and clinical function in patients with acute lumbosciatic pain and chronic low back pain — a 6 months prospective longitudinal study. Eur J Pain. 2006;10(8):711–9. https://doi.org/10.1016/j.ejpain.2005.11.005</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Stürmer T., Raum E., Buchner M., Gebhardt K., Schiltenwolf M., Richter W., Brenner H. Pain and high sensitivity C reactive protein in patients with chronic low back pain and acute sciatic pain. Ann Rheum Dis. 2005;64(6):921–5. https://doi.org/10.1136/ard.2004.027045</mixed-citation><mixed-citation xml:lang="en">Stürmer T., Raum E., Buchner M., Gebhardt K., Schiltenwolf M., Richter W., Brenner H. Pain and high sensitivity C reactive protein in patients with chronic low back pain and acute sciatic pain. Ann Rheum Dis. 2005;64(6):921–5. https://doi.org/10.1136/ard.2004.027045</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Wang X., Jia R., Li J., Zhu Y., Liu H., Wang W. et al. Research Progress on the Mechanism of Lumbarmultifidus Injury and Degeneration. Oxid Med Cell Longev. 2021;2021:6629037. https://oi.org/10.1155/2021/6629037</mixed-citation><mixed-citation xml:lang="en">Wang X., Jia R., Li J., Zhu Y., Liu H., Wang W. et al. Research Progress on the Mechanism of Lumbarmultifidus Injury and Degeneration. Oxid Med Cell Longev. 2021;2021:6629037. https://oi.org/10.1155/2021/6629037</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Ren K., Dubner R. Interactions between the immune and nervous systems in pain. Nature Medicine. 2010;16(11):1267–76. https://doi.org/10.1038/nm.2234</mixed-citation><mixed-citation xml:lang="en">Ren K., Dubner R. Interactions between the immune and nervous systems in pain. Nature Medicine. 2010;16(11):1267–76. https://doi.org/10.1038/nm.2234</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Lu L., Hu J., Wu Q., An Y., Cui W., Wang J., Ye Z. Berberine prevents human nucleus pulposus cells from IL1βinduced extracellular matrix degradation and apoptosis by inhibiting the NFκB pathway. Int J Mol Med. 2019;43(4):1679–1686. https://doi.org/10.3892/ijmm.2019.4105</mixed-citation><mixed-citation xml:lang="en">Lu L., Hu J., Wu Q., An Y., Cui W., Wang J., Ye Z. Berberine prevents human nucleus pulposus cells from IL1βinduced extracellular matrix degradation and apoptosis by inhibiting the NFκB pathway. Int J Mol Med. 2019;43(4):1679–1686. https://doi.org/10.3892/ijmm.2019.4105</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Hu J., Yan Q., Shi C., Tian Y., Cao P., Yuan W. BMSC paracrine activity attenuates interleukin-1β-induced inflammation and apoptosis in rat AF cells via inhibiting relative NF-κB signaling and the mitochondrial pathway. Am J Transl Res. 2017;9(1):79–89.</mixed-citation><mixed-citation xml:lang="en">Hu J., Yan Q., Shi C., Tian Y., Cao P., Yuan W. BMSC paracrine activity attenuates interleukin-1β-induced inflammation and apoptosis in rat AF cells via inhibiting relative NF-κB signaling and the mitochondrial pathway. Am J Transl Res. 2017;9(1):79–89.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Wang K., Chen T., Ying X., Zhang Z., Shao Z., Lin J. et al. Ligustilide alleviated IL-1β induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo. Int Immunopharmacol. 2019;69:398–407. https://doi.org/10.1016/j.intimp.2019.01.004</mixed-citation><mixed-citation xml:lang="en">Wang K., Chen T., Ying X., Zhang Z., Shao Z., Lin J. et al. Ligustilide alleviated IL-1β induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo. Int Immunopharmacol. 2019;69:398–407. https://doi.org/10.1016/j.intimp.2019.01.004</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Wang S.L., Yu Y.L., Tang C.L., Lv F.Z. Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration. Exp Ther Med. 2013;6(6):1522–1526. https://doi.org/10.3892/etm.2013.1348</mixed-citation><mixed-citation xml:lang="en">Wang S.L., Yu Y.L., Tang C.L., Lv F.Z. Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration. Exp Ther Med. 2013;6(6):1522–1526. https://doi.org/10.3892/etm.2013.1348</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Li X., Lin F., Wu Y., Liu N., Wang J., Chen R., Lu Z. Resveratrol attenuates inflammation environment-induced nucleus pulposus cell senescence in vitro. Biosci Rep. 2019;39(5):BSR20190126. https://doi.org/10.1042/BSR20190126</mixed-citation><mixed-citation xml:lang="en">Li X., Lin F., Wu Y., Liu N., Wang J., Chen R., Lu Z. Resveratrol attenuates inflammation environment-induced nucleus pulposus cell senescence in vitro. Biosci Rep. 2019;39(5):BSR20190126. https://doi.org/10.1042/BSR20190126</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Shamji M.F., Setton L.A., Jarvis W., So S., Chen J., Jing L. et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum. 2010;62(7):1974–1982. https://doi.org/10.1002/art.27444</mixed-citation><mixed-citation xml:lang="en">Shamji M.F., Setton L.A., Jarvis W., So S., Chen J., Jing L. et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum. 2010;62(7):1974–1982. https://doi.org/10.1002/art.27444</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Moen A., Lind A.L., Thulin M., Kamali-Moghaddam M., Røe C., Gjerstad J., Gordh T. Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation. Int J Inflam. 2016;2016:3874964. https://doi.org/10.1155/2016/3874964</mixed-citation><mixed-citation xml:lang="en">Moen A., Lind A.L., Thulin M., Kamali-Moghaddam M., Røe C., Gjerstad J., Gordh T. Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation. Int J Inflam. 2016;2016:3874964. https://doi.org/10.1155/2016/3874964</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Wang K., Bao J.P., Yang S., Hong X., Liu L., Xie X.H., Wu X.T. A cohort study comparing the serum levels of pro- or anti-inflammatory cytokines in patients with lumbar radicular pain and healthy subjects. Eur Spine J. 2016;25(5):1428–1434. https://doi.org/10.1007/s00586-015-4349-4</mixed-citation><mixed-citation xml:lang="en">Wang K., Bao J.P., Yang S., Hong X., Liu L., Xie X.H., Wu X.T. A cohort study comparing the serum levels of pro- or anti-inflammatory cytokines in patients with lumbar radicular pain and healthy subjects. Eur Spine J. 2016;25(5):1428–1434. https://doi.org/10.1007/s00586-015-4349-4</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Palada V., Ahmed A.S., Finn A., Berg S., Svensson C.I., Kosek E. Characterization of neuroinflammation and periphery-to-CNS inflammatory cross-talk in patients with disc herniation and degenerative disc disease. Brain Behav Immun. 2019;75:60–71. https://doi.org/10.1016/j.bbi.2018.09.010</mixed-citation><mixed-citation xml:lang="en">Palada V., Ahmed A.S., Finn A., Berg S., Svensson C.I., Kosek E. Characterization of neuroinflammation and periphery-to-CNS inflammatory cross-talk in patients with disc herniation and degenerative disc disease. Brain Behav Immun. 2019;75:60–71. https://doi.org/10.1016/j.bbi.2018.09.010</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Aripaka S.S., Bech-Azeddine R., Jørgensen L.M., Chughtai S.A., Gaarde C., Bendix T., Mikkelsen J.D. Low back pain scores correlate with the cytokine mRNA level in lumbar disc biopsies: a study of inflammatory markers in patients undergoing lumbar spinal fusion. Eur Spine J. 2021;30(10):2967–2974. https://doi.org/10.1007/s00586-021-06868-3</mixed-citation><mixed-citation xml:lang="en">Aripaka S.S., Bech-Azeddine R., Jørgensen L.M., Chughtai S.A., Gaarde C., Bendix T., Mikkelsen J.D. Low back pain scores correlate with the cytokine mRNA level in lumbar disc biopsies: a study of inflammatory markers in patients undergoing lumbar spinal fusion. Eur Spine J. 2021;30(10):2967–2974. https://doi.org/10.1007/s00586-021-06868-3</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Pedersen L.M., Schistad E, Jacobsen LM, Røe C, Gjerstad J. Serum levels of the pro-inflammatory interleukins 6 (IL-6) and -8 (IL-8) in patients with lumbar radicular pain due to disc herniation: A 12-month prospective study. Brain Behav Immun. 2015;46:132–6. https://doi.org/10.1016/j.bbi.2015.01.008</mixed-citation><mixed-citation xml:lang="en">Pedersen L.M., Schistad E, Jacobsen LM, Røe C, Gjerstad J. Serum levels of the pro-inflammatory interleukins 6 (IL-6) and -8 (IL-8) in patients with lumbar radicular pain due to disc herniation: A 12-month prospective study. Brain Behav Immun. 2015;46:132–6. https://doi.org/10.1016/j.bbi.2015.01.008</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Weber K.T., Alipui D.O., Sison C.P., Bloom O., Quraishi S., Overby M.C. et al. Serum levels of the proinflammatory cytokine interleukin-6 vary based on diagnoses in individuals with lumbar intervertebral disc diseases. Arthritis Res Ther. 2016;18:3. https://doi.org/10.1186/s13075-015-0887-8</mixed-citation><mixed-citation xml:lang="en">Weber K.T., Alipui D.O., Sison C.P., Bloom O., Quraishi S., Overby M.C. et al. Serum levels of the proinflammatory cytokine interleukin-6 vary based on diagnoses in individuals with lumbar intervertebral disc diseases. Arthritis Res Ther. 2016;18:3. https://doi.org/10.1186/s13075-015-0887-8</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Le Maitre C.L., Freemont A.J., Hoyland J.A. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther. 2005;7(4):R732–45. https://doi.org/10.1186/ar1732</mixed-citation><mixed-citation xml:lang="en">Le Maitre C.L., Freemont A.J., Hoyland J.A. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther. 2005;7(4):R732–45. https://doi.org/10.1186/ar1732</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Murata Y., Rydevik B., Nannmark U., Larsson K., Takahashi K.,Kato Y., Olmarker K. Local application of interleukin-6 to the dorsal root ganglion induces tumor necrosis factor-α in the dorsal root ganglion and results in apoptosis of the dorsal root ganglion cells. Spine (Phila Pa 1976). 2011;36(12):926–32. https://doi.org/10.1097/BRS.0b013e3181e7f4a9</mixed-citation><mixed-citation xml:lang="en">Murata Y., Rydevik B., Nannmark U., Larsson K., Takahashi K.,Kato Y., Olmarker K. Local application of interleukin-6 to the dorsal root ganglion induces tumor necrosis factor-α in the dorsal root ganglion and results in apoptosis of the dorsal root ganglion cells. Spine (Phila Pa 1976). 2011;36(12):926–32. https://doi.org/10.1097/BRS.0b013e3181e7f4a9</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Zu B., Pan H., Zhang X.J., Yin Z.S. Serum Levels of the Inflammatory Cytokines in Patients with Lumbar Radicular Pain Due to Disc Herniation. Asian Spine J. 2016;10(5):843–849. https://doi.org/10.4184/asj.2016.10.5.843</mixed-citation><mixed-citation xml:lang="en">Zu B., Pan H., Zhang X.J., Yin Z.S. Serum Levels of the Inflammatory Cytokines in Patients with Lumbar Radicular Pain Due to Disc Herniation. Asian Spine J. 2016;10(5):843–849. https://doi.org/10.4184/asj.2016.10.5.843</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Uçeyler N., Rogausch J.P., Toyka K.V., Sommer C. Differential expression of cytokines in painful and painless neuropathies. Neurology. 2007;69(1):42–49. https://doi.org/10.1212/01.wnl.0000265062.92340.a5</mixed-citation><mixed-citation xml:lang="en">Uçeyler N., Rogausch J.P., Toyka K.V., Sommer C. Differential expression of cytokines in painful and painless neuropathies. Neurology. 2007;69(1):42–49. https://doi.org/10.1212/01.wnl.0000265062.92340.a5</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Wang D.L., Jiang S.D., Dai L.Y. Biologic response of the intervertebral disc to static and dynamic compression in vitro. Spine (Phila Pa 1976). 2007;32(23):2521–8. https://doi.org/10.1097/BRS.0b013e318158cb61</mixed-citation><mixed-citation xml:lang="en">Wang D.L., Jiang S.D., Dai L.Y. Biologic response of the intervertebral disc to static and dynamic compression in vitro. Spine (Phila Pa 1976). 2007;32(23):2521–8. https://doi.org/10.1097/BRS.0b013e318158cb61</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Walter B.A., Likhitpanichkul M., Illien-Junger S., Roughley P.J., Hecht A.C., Iatridis J.C. TNF-α transport induced by dynamic loading alters biomechanics of intact intervertebral discs. PLoS One. 2015;10(3):e0118358. https://doi.org/10.1371/journal.pone.0118358</mixed-citation><mixed-citation xml:lang="en">Walter B.A., Likhitpanichkul M., Illien-Junger S., Roughley P.J., Hecht A.C., Iatridis J.C. TNF-α transport induced by dynamic loading alters biomechanics of intact intervertebral discs. PLoS One. 2015;10(3):e0118358. https://doi.org/10.1371/journal.pone.0118358</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Séguin C.A., Pilliar R.M., Roughley P.J., Kandel R.A. Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue. Spine (Phila Pa 1976). 2005;30(17):1940–8. https://doi.org/10.1097/01.brs.0000176188.40263.f9</mixed-citation><mixed-citation xml:lang="en">Séguin C.A., Pilliar R.M., Roughley P.J., Kandel R.A. Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue. Spine (Phila Pa 1976). 2005;30(17):1940–8. https://doi.org/10.1097/01.brs.0000176188.40263.f9</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Ponnappan R.K., Markova D.Z., Antonio P.J., Murray H.B., Vaccaro A.R., Shapiro I.M. et al. An organ culture system to model early degenerative changes of the intervertebral disc. Arthritis Res Ther. 2011;13(5):R171. https://doi.org/10.1186/ar3494</mixed-citation><mixed-citation xml:lang="en">Ponnappan R.K., Markova D.Z., Antonio P.J., Murray H.B., Vaccaro A.R., Shapiro I.M. et al. An organ culture system to model early degenerative changes of the intervertebral disc. Arthritis Res Ther. 2011;13(5):R171. https://doi.org/10.1186/ar3494</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Hayashi S., Taira A., Inoue G., Koshi T., Ito T., Yamashita M. et al. TNF-alpha in nucleus pulposus induces sensory nerve growth: a study of the mechanism of discogenic low back pain using TNFalpha-deficient mice. Spine (Phila Pa 1976). 2008;33(14):1542–6. https://doi.org/10.1097/BRS.0b013e318178e5ea</mixed-citation><mixed-citation xml:lang="en">Hayashi S., Taira A., Inoue G., Koshi T., Ito T., Yamashita M. et al. TNF-alpha in nucleus pulposus induces sensory nerve growth: a study of the mechanism of discogenic low back pain using TNFalpha-deficient mice. Spine (Phila Pa 1976). 2008;33(14):1542–6. https://doi.org/10.1097/BRS.0b013e318178e5ea</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Le Maitre C.L., Hoyland J.A., Freemont A.J. Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile. Arthritis Res Ther. 2007;9(4):R77. https://doi.org/10.1186/ar2275</mixed-citation><mixed-citation xml:lang="en">Le Maitre C.L., Hoyland J.A., Freemont A.J. Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile. Arthritis Res Ther. 2007;9(4):R77. https://doi.org/10.1186/ar2275</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Li Y., Liu J., Liu Z.Z., Duan D.P. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker. Biosci Rep. 2016;36(4). https://doi.org/10.1042/BSR20160187</mixed-citation><mixed-citation xml:lang="en">Li Y., Liu J., Liu Z.Z., Duan D.P. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker. Biosci Rep. 2016;36(4). https://doi.org/10.1042/BSR20160187</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">van den Berg R., Jongbloed E.M., de Schepper E., Bierma-Zeinstra S., Koes B.W., Luijsterburg P. The association between pro-inflammatory biomarkers and nonspecific low back pain: a systematic review. Spine J. 2018;18(11):2140–2151. https://doi.org/10.1016/j.spinee.2018.06.349</mixed-citation><mixed-citation xml:lang="en">van den Berg R., Jongbloed E.M., de Schepper E., Bierma-Zeinstra S., Koes B.W., Luijsterburg P. The association between pro-inflammatory biomarkers and nonspecific low back pain: a systematic review. Spine J. 2018;18(11):2140–2151. https://doi.org/10.1016/j.spinee.2018.06.349</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">García-Cosamalón J., del Valle M.E., Calavia M.G., GarcíaSuárez O., López-Muñiz A., Otero J., Vega J.A. Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain? J Anat. 2010;217(1):1–15. https://doi.org/10.1111/j.1469-7580.2010.01227.x</mixed-citation><mixed-citation xml:lang="en">García-Cosamalón J., del Valle M.E., Calavia M.G., GarcíaSuárez O., López-Muñiz A., Otero J., Vega J.A. Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain? J Anat. 2010;217(1):1–15. https://doi.org/10.1111/j.1469-7580.2010.01227.x</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Wuertz K., Haglund L. Inflammatory mediators in intervertebral disk degeneration and discogenic pain. Global Spine J. 2013;3(3):175–184. https://doi.org/10.1055/s-0033-1347299</mixed-citation><mixed-citation xml:lang="en">Wuertz K., Haglund L. Inflammatory mediators in intervertebral disk degeneration and discogenic pain. Global Spine J. 2013;3(3):175–184. https://doi.org/10.1055/s-0033-1347299</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Johnson W.E., Caterson B., Eisenstein S.M., Hynds D.L., Snow D.M., Roberts S. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum. 2002;46(10):2658–2664. https://doi.org/10.1002/art.10585</mixed-citation><mixed-citation xml:lang="en">Johnson W.E., Caterson B., Eisenstein S.M., Hynds D.L., Snow D.M., Roberts S. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum. 2002;46(10):2658–2664. https://doi.org/10.1002/art.10585</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Peng B., Wu W., Hou S., Li P., Zhang C., Yang Y. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br. 2005;87(1):62–67. PMID: 15686239.</mixed-citation><mixed-citation xml:lang="en">Peng B., Wu W., Hou S., Li P., Zhang C., Yang Y. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br. 2005;87(1):62–67. PMID: 15686239.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Risbud M.V., Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol. 2014;10(1):44–56. https://doi.org/10.1038/nrrheum.2013.160</mixed-citation><mixed-citation xml:lang="en">Risbud M.V., Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol. 2014;10(1):44–56. https://doi.org/10.1038/nrrheum.2013.160</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">van den Berg R., Jongbloed E.M., de Schepper E.I.T., BiermaZeinstra S.M.A., Koes B.W., Luijsterburg P.A.J. The association between pro-inflammatory biomarkers and nonspecific low back pain: a systematic review. Spine J. 2018;18(11):2140–2151. https://doi.org/10.1016/j.spinee.2018.06.349</mixed-citation><mixed-citation xml:lang="en">van den Berg R., Jongbloed E.M., de Schepper E.I.T., BiermaZeinstra S.M.A., Koes B.W., Luijsterburg P.A.J. The association between pro-inflammatory biomarkers and nonspecific low back pain: a systematic review. Spine J. 2018;18(11):2140–2151. https://doi.org/10.1016/j.spinee.2018.06.349</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Shamji M.F., Setton L.A., Jarvis W., So S., Chen J., Jing L. et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum. 2010;62(7):1974–82. https://doi.org/10.1002/art.27444</mixed-citation><mixed-citation xml:lang="en">Shamji M.F., Setton L.A., Jarvis W., So S., Chen J., Jing L. et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum. 2010;62(7):1974–82. https://doi.org/10.1002/art.27444</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Korhonen T., Karppinen J., Malmivaara A., Autio R., Niinimäki J., Paimela L. et al. Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up. Spine (Phila Pa 1976). 2004;29(19):2115–9. https://doi.org/10.1097/01.brs.0000141179.58778.6c</mixed-citation><mixed-citation xml:lang="en">Korhonen T., Karppinen J., Malmivaara A., Autio R., Niinimäki J., Paimela L. et al. Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up. Spine (Phila Pa 1976). 2004;29(19):2115–9. https://doi.org/10.1097/01.brs.0000141179.58778.6c</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Finnerup N.B., Attal N., Haroutounian S., McNicol E., Baron R.,Dworkin R.H. et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–73. https://doi.org/10.1016/S1474-4422(14)70251-0</mixed-citation><mixed-citation xml:lang="en">Finnerup N.B., Attal N., Haroutounian S., McNicol E., Baron R.,Dworkin R.H. et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–73. https://doi.org/10.1016/S1474-4422(14)70251-0</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Kadow T., Sowa G., Vo N., Kang J.D. Molecular basis of intervertebral disc degeneration and herniations: what are the important translational questions. Clin Orthop Relat Res. 2015;473(6):1903–1912. https://doi.org/10.1007/s11999-014-3774-8</mixed-citation><mixed-citation xml:lang="en">Kadow T., Sowa G., Vo N., Kang J.D. Molecular basis of intervertebral disc degeneration and herniations: what are the important translational questions. Clin Orthop Relat Res. 2015;473(6):1903–1912. https://doi.org/10.1007/s11999-014-3774-8</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Kim J.H., Choi H., Suh M.J., Shin J.H., Hwang M.H., Lee H.M. Effect of biphasic electrical current stimulation on IL-1β-stimulated annulus fibrosus cells using in vitro microcurrent generating chamber system. Spine (Phila Pa 1976). 2013;38(22):E1368 —76. https://doi.org/10.1097/BRS.0b013e3182a211e3</mixed-citation><mixed-citation xml:lang="en">Kim J.H., Choi H., Suh M.J., Shin J.H., Hwang M.H., Lee H.M. Effect of biphasic electrical current stimulation on IL-1β-stimulated annulus fibrosus cells using in vitro microcurrent generating chamber system. Spine (Phila Pa 1976). 2013;38(22):E1368 —76. https://doi.org/10.1097/BRS.0b013e3182a211e3</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Zhan S., Wang K., Song Y., Li S., Yin H., Luo R. et al. Long non-coding RNA HOTAIR modulates intervertebral disc degenerative changes via Wnt/β-catenin pathway. Arthritis Res Ther. 2019;21(1):201. https://doi.org/10.1186/s13075-019-1986-8</mixed-citation><mixed-citation xml:lang="en">Zhan S., Wang K., Song Y., Li S., Yin H., Luo R. et al. Long non-coding RNA HOTAIR modulates intervertebral disc degenerative changes via Wnt/β-catenin pathway. Arthritis Res Ther. 2019;21(1):201. https://doi.org/10.1186/s13075-019-1986-8</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Fang W., Zhou X., Wang J., Xu L., Zhou L., Yu W. et al. Wogonin mitigates intervertebral disc degeneration through the Nrf2/ARE and MAPK signaling pathways. Int Immunopharmacol. 2018;65:539–549. https://doi.org/10.1016/j.intimp.2018.10.024</mixed-citation><mixed-citation xml:lang="en">Fang W., Zhou X., Wang J., Xu L., Zhou L., Yu W. et al. Wogonin mitigates intervertebral disc degeneration through the Nrf2/ARE and MAPK signaling pathways. Int Immunopharmacol. 2018;65:539–549. https://doi.org/10.1016/j.intimp.2018.10.024</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Johnson W.E., Caterson B., Eisenstein S.M., Hynds D.L., Snow D.M., Roberts S. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum. 2002;46(10):2658–2664. https://doi.org/10.1002/art.10585</mixed-citation><mixed-citation xml:lang="en">Johnson W.E., Caterson B., Eisenstein S.M., Hynds D.L., Snow D.M., Roberts S. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum. 2002;46(10):2658–2664. https://doi.org/10.1002/art.10585</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Liu X.W., Kang J., Fan X.D., Sun L.F. Expression and significance of VEGF and p53 in rat degenerated intervertebral disc tissues. Asian Pac J Trop Med. 2013;6(5):404–6. https://doi.org/10.1016/S1995-7645(13)60047-4</mixed-citation><mixed-citation xml:lang="en">Liu X.W., Kang J., Fan X.D., Sun L.F. Expression and significance of VEGF and p53 in rat degenerated intervertebral disc tissues. Asian Pac J Trop Med. 2013;6(5):404–6. https://doi.org/10.1016/S1995-7645(13)60047-4</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Hsu YH, Lin RM, Chiu YS, Liu WL, Huang KY. Effects of IL-1β, IL-20, and BMP-2 on Intervertebral Disc Inflammation under Hypoxia. J Clin Med. 2020 Jan 4;9(1):140. https://doi.org/10.3390/jcm9010140</mixed-citation><mixed-citation xml:lang="en">Hsu YH, Lin RM, Chiu YS, Liu WL, Huang KY. Effects of IL-1β, IL-20, and BMP-2 on Intervertebral Disc Inflammation under Hypoxia. J Clin Med. 2020 Jan 4;9(1):140. https://doi.org/10.3390/jcm9010140</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Kwon W.K., Moon H.J., Kwon T.H., Park Y.K., Kim J.H. The Role of Hypoxia in Angiogenesis and Extracellular Matrix Regulation of Intervertebral Disc Cells During Inflammatory Reactions. Neurosurgery. 2017;81(5):867–875. https://doi.org/10.1093/neuros/nyx149</mixed-citation><mixed-citation xml:lang="en">Kwon W.K., Moon H.J., Kwon T.H., Park Y.K., Kim J.H. The Role of Hypoxia in Angiogenesis and Extracellular Matrix Regulation of Intervertebral Disc Cells During Inflammatory Reactions. Neurosurgery. 2017;81(5):867–875. https://doi.org/10.1093/neuros/nyx149</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Autio R.A., Karppinen J., Niinimäki J., Ojala R., Kurunlahti M., Haapea M. et al. Determinants of spontaneous resorption of intervertebral disc herniations. Spine. 2006;31(11):1247–1252. https://doi.org/10.1097/01.brs.0000217681.83524.4a</mixed-citation><mixed-citation xml:lang="en">Autio R.A., Karppinen J., Niinimäki J., Ojala R., Kurunlahti M., Haapea M. et al. Determinants of spontaneous resorption of intervertebral disc herniations. Spine. 2006;31(11):1247–1252. https://doi.org/10.1097/01.brs.0000217681.83524.4a</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Kobayashi S., Meir A., Kokubo Y., Uchida K., Takeno K., Miyazaki T. et al. Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias. Spine. 2009;34(7):655–662. https://doi.org/10.1097/BRS.0b013e31819c9d5b</mixed-citation><mixed-citation xml:lang="en">Kobayashi S., Meir A., Kokubo Y., Uchida K., Takeno K., Miyazaki T. et al. Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias. Spine. 2009;34(7):655–662. https://doi.org/10.1097/BRS.0b013e31819c9d5b</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Molinos M., Almeida C.R., Caldeira J., Cunha C., Gon-çalves R.M., Barbosa M.A. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface. 2015;12(104):20141191. https://doi.org/10.1098/rsif.2014.1191</mixed-citation><mixed-citation xml:lang="en">Molinos M., Almeida C.R., Caldeira J., Cunha C., Gon-çalves R.M., Barbosa M.A. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface. 2015;12(104):20141191. https://doi.org/10.1098/rsif.2014.1191</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>
