<?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">vedomostiregmed</journal-id><journal-title-group><journal-title xml:lang="ru">Регуляторные исследования и экспертиза лекарственных средств</journal-title><trans-title-group xml:lang="en"><trans-title>Regulatory Research and Medicine Evaluation</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">3034-3062</issn><issn pub-type="epub">3034-3453</issn><publisher><publisher-name>Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30895/1991-2919-2026-16-1-76-91</article-id><article-id custom-type="elpub" pub-id-type="custom">vedomostiregmed-829</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>ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PRECLINICAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Ноцицептивные тесты в мультимодальной оценке боли в доклинических исследованиях (обзор)</article-title><trans-title-group xml:lang="en"><trans-title>Nociceptive Tests as Part of Multimodal Pain Assessment in Preclinical Trials (Review)</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-7410-8562</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Суров</surname><given-names>Д. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Surov</surname><given-names>D. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Суров Дмитрий Викторович</p><p>ул. Лесопарковая, д. 4, Санкт-Петербург, 195043; ул. Академика Павлова, д. 12, лит. Д, Санкт-Петербург, 197022</p></bio><bio xml:lang="en"><p>Dmitry V. Surov </p><p>4 Lesoparkovaya Street, Saint Petersburg, 195043; 12 Acad. Pavlov Street, Saint Petersburg, 197022</p></bio><email xlink:type="simple">gniiivm_5@mil.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/0000-0001-8596-6469</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Коньшаков</surname><given-names>Ю. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Kon’shakov</surname><given-names>Ju. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Коньшаков Юрий Олегович, канд. мед. наук </p><p>ул. Лесопарковая, д. 4, Санкт-Петербург, 195043</p></bio><bio xml:lang="en"><p>Jurij O. Kon’shakov, Cand. Sci. (Med.)</p><p>4 Lesoparkovaya Street, Saint Petersburg, 195043</p></bio><email xlink:type="simple">gniiivm_5@mil.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3219-341X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Венгерович</surname><given-names>Н. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Vengerovich</surname><given-names>N. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Венгерович Николай Григорьевич, д-р мед. наук, профессор </p><p>ул. Лесопарковая, д. 4, Санкт-Петербург, 195043; ул. Проф. Попова д. 14, лит. А, Санкт-Петербург, 197376</p></bio><bio xml:lang="en"><p>Nickolai G. Vengerovich, Dr. Sci. (Med.), Professor</p><p>4 Lesoparkovaya Street, Saint Petersburg, 195043; 14 Professor Popov St., Saint Petersburg 197376</p></bio><email xlink:type="simple">gniiivm_5@mil.ru</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное учреждение «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны Российской Федерации ; Федеральное государственное бюджетное научное учреждение «Институт экспериментальной медицины»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>State Research Testing Institute of Military Medicine;&#13;
Institute of Experimental Medicine</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Федеральное государственное учреждение «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>State Research Testing Institute of Military Medicine</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Федеральное государственное учреждение «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны Российской Федерации;&#13;
Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>State Research Testing Institute of Military Medicine; Saint Petersburg State Chemical and Pharmaceutical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>07</day><month>03</month><year>2026</year></pub-date><volume>16</volume><issue>1</issue><fpage>76</fpage><lpage>91</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Суров Д.В., Коньшаков Ю.О., Венгерович Н.Г., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Суров Д.В., Коньшаков Ю.О., Венгерович Н.Г.</copyright-holder><copyright-holder xml:lang="en">Surov D.V., Kon’shakov J.O., Vengerovich N.G.</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.vedomostincesmp.ru/jour/article/view/829">https://www.vedomostincesmp.ru/jour/article/view/829</self-uri><abstract><sec><title>ВВЕДЕНИЕ</title><p>ВВЕДЕНИЕ. В настоящее время доклиническая разработка анальгетических препаратов в значительной степени ограничена валидностью моделей и методов оценки боли. Для преодоления трансляционного барьера при разработке обезболивающих средств необходимы ревизия существующих методов оценки болевой чувствительности и разработка новых подходов, которые включают исследование не только рефлекторного, но и аффективного компонента боли.</p></sec><sec><title>ЦЕЛЬ</title><p>ЦЕЛЬ. Систематизация современных представлений о методах оценки боли у лабораторных животных и определение критериев их применимости в доклинических исследованиях новых анальгетиков.</p></sec><sec><title>ОБСУЖДЕНИЕ</title><p>ОБСУЖДЕНИЕ. Обзор основан на анализе 75 научных публикаций (оригинальные исследования и систематические обзоры за последние 35 лет). Боль — многомерный феномен, включающий сенсорно-дискриминационный и аффективно-мотивационный компоненты. Стандартные ноцицептивные тесты характеризуются высокой оценочной эффективностью в отношении сенсорной гиперчувствительности, но оказываются недостаточно чувствительными для изучения хронической боли, в основе которой лежит аффективный компонент. Менее широко используемые нерефлекторные методы (шкала гримас, ультразвуковая вокализация, тест рытья нор) хотя и позволяют оценивать аффективный компонент, часто обладают низкой специфичностью и недостаточно валидированы на различных моделях боли. Комбинированный, полимодальный подход повышает объективность, воспроизводимость и трансляционную предиктивность доклинических исследований на пути к разработке новых анальгетиков.</p></sec><sec><title>ВЫВОДЫ</title><p>ВЫВОДЫ. Ноцицептивные тесты являются инструментом оценки эффективности обезболивающих средств как в рамках первичного скрининга, так и на этапе доклинических исследований. Стандартные ноцицептивные тесты не позволяют оценить аффективный компонент боли, поэтому разработка новых обезболивающих препаратов требует включения в программу доклинических исследований нерефлекторных методов оценки боли. Совместное использование рефлекторных и нерефлекторных методов оценки боли является основой разработки новых исследовательских стратегий в доклинических исследованиях.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>INTRODUCTION</title><p>INTRODUCTION. Currently, preclinical development of analgetic drugs is facing a large number of obstacles, mostly due to the limited validity of models and methods for pain assessment. To overcome the translational barrier in the development of analgetics, it is necessary to revise the existing methods for assessing pain sensitivity and develop new approaches that include both the study of reflexive and affective pain component.</p></sec><sec><title>AIM</title><p>AIM. This study aimed to systematize a contemporary view of pain assessment methods in laboratory animals and develop applicability criteria in preclinical trials of new analgesics.</p></sec><sec><title>DISCUSSION</title><p>DISCUSSION. The literature review included 75 references, among them original research and systematic reviews over the past 35 years. Pain is a multidimensional phenomenon that includes sensory, discriminatory and affective-motivational components. Standard nociceptive tests effectively evaluate sensory hypersensitivity, however, they are not sensitive enough when studying chronic pain based on an affective component. Less widely used non-reflexive methods (grimace scale, ultrasound vocalization, burrowing test) allow assessing the affective component; still, they have low specificity and are insufficiently validated for various pain models. A combined, polymodal approach enhances the objectivity, reproducibility, and translational predictivity of preclinical research towards the development of new analgetics.</p></sec><sec><title>CONCLUSIONS</title><p>CONCLUSIONS. Nociceptive tests are a tool for assessing efficacy of anesthetics both at a primary screening and in preclinical trials. Standard nociceptive tests do not allow assessing affective pain component, thus development of new anesthetics necessitates an introduction of non-reflexive pain assessment in the preclinical trials. A combination of reflexive and non-reflexive pain assessment methods is a base for new research strategies in preclinical trials.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>боль</kwd><kwd>ноцицептивная система</kwd><kwd>ноцицепция</kwd><kwd>ноцицептивные тесты</kwd><kwd>тест фон Фрея</kwd><kwd>тест отдергивания хвоста</kwd><kwd>тест горячая пластина</kwd><kwd>шкала гримас</kwd><kwd>ультразвуковая вокализация</kwd><kwd>этологический анализ</kwd><kwd>поведенческий анализ</kwd><kwd>доклинические исследования</kwd><kwd>трансляционные исследования</kwd></kwd-group><kwd-group xml:lang="en"><kwd>pain</kwd><kwd>nociceptive system</kwd><kwd>nociception</kwd><kwd>nociceptive tests</kwd><kwd>von Frey test</kwd><kwd>tail flick test</kwd><kwd>hot plate test</kwd><kwd>grimace scale</kwd><kwd>ultrasonic vocalization</kwd><kwd>behavioral analysis</kwd><kwd>preclinical trials</kwd><kwd>translational studies</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена без спонсорской поддержки.</funding-statement><funding-statement xml:lang="en">The study was performed without external funding.</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">Vierck CJ. Animal studies of pain: lessons for drug development. In: Campbell JN, ed. Emerging strategies for the treatment of neuropathic pain. Seattle: IASP Press; 2006. P. 475–95.</mixed-citation><mixed-citation xml:lang="en">Vierck CJ. Animal studies of pain: lessons for drug development. In: Campbell JN, ed. Emerging strategies for the treatment of neuropathic pain. Seattle: IASP Press; 2006. P. 475–95.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Hill R. NK1 (substance P) receptor antagonists — why are they not analgesic in humans? Trends Pharmacol Sci. 2000;21(7):244–6. https://doi.org/10.1016/s0165-6147(00)01502-9</mixed-citation><mixed-citation xml:lang="en">Hill R. NK1 (substance P) receptor antagonists — why are they not analgesic in humans? Trends Pharmacol Sci. 2000;21(7):244–6. https://doi.org/10.1016/s0165-6147(00)01502-9</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Wallace MS, Rowbotham M, Bennett GJ, et al. A multicenter, double-blind, randomized, placebo-controlled crossover evaluation of a short course of 4030W92 in patients with chronic neuropathic pain. J Pain. 2002;3(3):227–33. https://doi.org/10.1054/jpai.2002.123650</mixed-citation><mixed-citation xml:lang="en">Wallace MS, Rowbotham M, Bennett GJ, et al. A multicenter, double-blind, randomized, placebo-controlled crossover evaluation of a short course of 4030W92 in patients with chronic neuropathic pain. J Pain. 2002;3(3):227–33. https://doi.org/10.1054/jpai.2002.123650</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Davis KD, Aghaeepour N, Ahn AH, et al. Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities. Nat Rev Neurol. 2020;16(7):381–400. https://doi.org/10.1038/s41582-020-0362-2</mixed-citation><mixed-citation xml:lang="en">Davis KD, Aghaeepour N, Ahn AH, et al. Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities. Nat Rev Neurol. 2020;16(7):381–400. https://doi.org/10.1038/s41582-020-0362-2</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Mao J. Current challenges in translational pain research. Trends Pharmacol Sci. 2012;33(11):568–73. https://doi.org/10.1016/j.tips.2012.08.001</mixed-citation><mixed-citation xml:lang="en">Mao J. Current challenges in translational pain research. Trends Pharmacol Sci. 2012;33(11):568–73. https://doi.org/10.1016/j.tips.2012.08.001</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Asiri YI, Moni SS, Ramar M, Chidambaram K. Advancing pain understanding and drug discovery: Insights from preclinical models and recent research findings. Pharmaceuticals (Basel). 2024;17(11):1439. https://doi.org/10.3390/ph17111439</mixed-citation><mixed-citation xml:lang="en">Asiri YI, Moni SS, Ramar M, Chidambaram K. Advancing pain understanding and drug discovery: Insights from preclinical models and recent research findings. Pharmaceuticals (Basel). 2024;17(11):1439. https://doi.org/10.3390/ph17111439</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Mogil JS. Animal models of pain: Progress and challenges. Nat Rev Neurosci. 2009;10(4):283–94. https://doi.org/10.1038/nrn2606</mixed-citation><mixed-citation xml:lang="en">Mogil JS. Animal models of pain: Progress and challenges. Nat Rev Neurosci. 2009;10(4):283–94. https://doi.org/10.1038/nrn2606</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Mogil JS, Pang DSJ, Silva Dutra GG, Chambers CT. The development and use of facial grimace scales for pain measurement in animals. Neurosci Biobehav Rev. 2020;116:480–93. https://doi.org/10.1016/j.neubiorev.2020.07.013</mixed-citation><mixed-citation xml:lang="en">Mogil JS, Pang DSJ, Silva Dutra GG, Chambers CT. The development and use of facial grimace scales for pain measurement in animals. Neurosci Biobehav Rev. 2020;116:480–93. https://doi.org/10.1016/j.neubiorev.2020.07.013</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Burma NE, Leduc-Pessah H, Fan CY, Trang T. Animal models of chronic pain: Advances and challenges for clinical translation. J Neurosci Res. 2017;95(6):1242–56. https://doi.org/10.1002/jnr.23768</mixed-citation><mixed-citation xml:lang="en">Burma NE, Leduc-Pessah H, Fan CY, Trang T. Animal models of chronic pain: Advances and challenges for clinical translation. J Neurosci Res. 2017;95(6):1242–56. https://doi.org/10.1002/jnr.23768</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Reid J, Scott M, Nolan A, Wiseman-Orr L. Pain assessment in animals. In Pract. 2013;35(2):51–6. https://doi.org/10.1136/inp.f631</mixed-citation><mixed-citation xml:lang="en">Reid J, Scott M, Nolan A, Wiseman-Orr L. Pain assessment in animals. In Pract. 2013;35(2):51–6. https://doi.org/10.1136/inp.f631</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Weary DM, Niel L, Flower FC, Fraser D. Identifying and preventing pain in animals. Appl Anim Behav Sci. 2006;100(1–2):64–76. https://doi.org/10.1016/j.applanim.2006.04.013</mixed-citation><mixed-citation xml:lang="en">Weary DM, Niel L, Flower FC, Fraser D. Identifying and preventing pain in animals. Appl Anim Behav Sci. 2006;100(1–2):64–76. https://doi.org/10.1016/j.applanim.2006.04.013</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Modi AD, Parekh A, Pancholi YN. Evaluating pain behaviours: Widely used mechanical and thermal methods in rodents. Behav Brain Res. 2023;446:114417. https://doi.org/10.1016/j.bbr.2023.114417</mixed-citation><mixed-citation xml:lang="en">Modi AD, Parekh A, Pancholi YN. Evaluating pain behaviours: Widely used mechanical and thermal methods in rodents. Behav Brain Res. 2023;446:114417. https://doi.org/10.1016/j.bbr.2023.114417</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Sneddon LU. Evolution of nociception in vertebrates: comparative analysis of lower vertebrates. Brain Res Rev. 2004;46(2):123–30. https://doi.org/10.1016/j.brainresrev.2004.07.007</mixed-citation><mixed-citation xml:lang="en">Sneddon LU. Evolution of nociception in vertebrates: comparative analysis of lower vertebrates. Brain Res Rev. 2004;46(2):123–30. https://doi.org/10.1016/j.brainresrev.2004.07.007</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Loeser JD, Treede RD. The Kyoto protocol of IASP Basic Pain Terminology. Pain. 2008;137(3):473–7. https://doi.org/10.1016/j.pain.2008.04.025</mixed-citation><mixed-citation xml:lang="en">Loeser JD, Treede RD. The Kyoto protocol of IASP Basic Pain Terminology. Pain. 2008;137(3):473–7. https://doi.org/10.1016/j.pain.2008.04.025</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Данилов АБ. Нейропатическая боль. Клиническая геронтология. 2007;13(2):27–36. EDN: JHCZAB</mixed-citation><mixed-citation xml:lang="en">Danilov AB. Neuropathic pain. Clinical Gerontology. 2007;13(2):27–36 (In Russ.). EDN: JHCZAB</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Данилов АБ, Исагулян ЭД, Макашова ЕС. Психогенная боль. Журнал неврологии и психиатрии им. C.C. Корсакова. 2018;118(11):103–8. https://doi.org/10.17116/jnevro2018118111103</mixed-citation><mixed-citation xml:lang="en">Danilov AB, Isagulyan ED, Macka-schova ES. Psychogenic pain. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(11):103–8 (In Russ.). https://doi.org/10.17116/jnevro2018118111103</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Kosek E. The concept of nociplastic pain — where to from here? Pain. 2024;165(11):50–7. https://doi.org/10.1097/j.pain.0000000000003305</mixed-citation><mixed-citation xml:lang="en">Kosek E. The concept of nociplastic pain — where to from here? Pain. 2024;165(11):50–7. https://doi.org/10.1097/j.pain.0000000000003305</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">McKune CM, Murrell JC, Nolan AM, et al. Nociception and pain. Veterinary anesthesia and analgesia. Wiley; 2015. https://doi.org/10.1002/9781119421375.ch29</mixed-citation><mixed-citation xml:lang="en">McKune CM, Murrell JC, Nolan AM, et al. Nociception and pain. Veterinary anesthesia and analgesia. Wiley; 2015. https://doi.org/10.1002/9781119421375.ch29</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Price DD. Central neural mechanisms that interrelate sensory and affective dimensions of pain. Mol Inter. 2002;2(6):392–403. https://doi.org/10.1124/mi.2.6.392</mixed-citation><mixed-citation xml:lang="en">Price DD. Central neural mechanisms that interrelate sensory and affective dimensions of pain. Mol Inter. 2002;2(6):392–403. https://doi.org/10.1124/mi.2.6.392</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Djouhri L, Koutsikou S, Fang X, et al. Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J Neurosci. 2006;26(4):1281–92. https://doi.org/10.1523/JNEUROSCI.3388-05.2006</mixed-citation><mixed-citation xml:lang="en">Djouhri L, Koutsikou S, Fang X, et al. Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J Neurosci. 2006;26(4):1281–92. https://doi.org/10.1523/JNEUROSCI.3388-05.2006</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Hansson P. Difficulties in stratifying neuropathic pain by mechanisms. Eur J Pain. 2003;7(4):353–7. https://doi.org/10.1016/S1090-3801(03)00051-X</mixed-citation><mixed-citation xml:lang="en">Hansson P. Difficulties in stratifying neuropathic pain by mechanisms. Eur J Pain. 2003;7(4):353–7. https://doi.org/10.1016/S1090-3801(03)00051-X</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Sneddon LU, Elwood RW, Adamo SA, Leach MC. Defining and assessing animal pain. Anim Behav. 2014;97:201–12. https://doi.org/10.1016/j.anbehav.2014.09.007</mixed-citation><mixed-citation xml:lang="en">Sneddon LU, Elwood RW, Adamo SA, Leach MC. Defining and assessing animal pain. Anim Behav. 2014;97:201–12. https://doi.org/10.1016/j.anbehav.2014.09.007</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Talbot K, Madden VJ, Jones SL, Moseley GL. The sensory and affective components of pain: are they differentially modifiable dimensions or inseparable aspects of a unitary experience? A systematic review. Br J Anaesth. 2019;123(2):263–72. https://doi.org/10.1016/j.bja.2019.03.033</mixed-citation><mixed-citation xml:lang="en">Talbot K, Madden VJ, Jones SL, Moseley GL. The sensory and affective components of pain: are they differentially modifiable dimensions or inseparable aspects of a unitary experience? A systematic review. Br J Anaesth. 2019;123(2):263–72. https://doi.org/10.1016/j.bja.2019.03.033</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Ong WY, Stohler CS, Herr DR. Role of the prefrontal cortex in pain processing. Mol Neurobiol. 2019;56(2):1137–66. https://doi.org/10.1007/s12035-018-1130-9</mixed-citation><mixed-citation xml:lang="en">Ong WY, Stohler CS, Herr DR. Role of the prefrontal cortex in pain processing. Mol Neurobiol. 2019;56(2):1137–66. https://doi.org/10.1007/s12035-018-1130-9</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Labrakakis C. The role of the insular cortex in pain. Int J Mol Sci. 2023;24(6):5736. https://doi.org/10.3390/ijms24065736</mixed-citation><mixed-citation xml:lang="en">Labrakakis C. The role of the insular cortex in pain. Int J Mol Sci. 2023;24(6):5736. https://doi.org/10.3390/ijms24065736</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Langford DJ, Crager SE, Shehzad Z, et al. Social modulation of pain as evidence for empathy in mice. Science. 2006; 312(5782):1967–70. https://doi.org/10.1126/science.1128322</mixed-citation><mixed-citation xml:lang="en">Langford DJ, Crager SE, Shehzad Z, et al. Social modulation of pain as evidence for empathy in mice. Science. 2006; 312(5782):1967–70. https://doi.org/10.1126/science.1128322</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Langford DJ, Bailey AL, Chanda ML, et al. Coding of facial expressions of pain in the laboratory mouse. Nat Methods. 2010;7(6):447–9. https://doi.org/10.1038/nmeth.1455</mixed-citation><mixed-citation xml:lang="en">Langford DJ, Bailey AL, Chanda ML, et al. Coding of facial expressions of pain in the laboratory mouse. Nat Methods. 2010;7(6):447–9. https://doi.org/10.1038/nmeth.1455</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang XJ, Zhang TW, Hu SJ, Xu H. Behavioral assessments of the aversive quality of pain in animals. Neurosci Bull. 2011; 27(1):61–7. https://doi.org/10.1007/s12264-011-1035-3</mixed-citation><mixed-citation xml:lang="en">Zhang XJ, Zhang TW, Hu SJ, Xu H. Behavioral assessments of the aversive quality of pain in animals. Neurosci Bull. 2011; 27(1):61–7. https://doi.org/10.1007/s12264-011-1035-3</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Sneddon LU. Comparative physiology of nociception and pain. Physiology (Bethesda). 2018;33(1):63–73. https://doi.org/10.1152/physiol.00022.2017</mixed-citation><mixed-citation xml:lang="en">Sneddon LU. Comparative physiology of nociception and pain. Physiology (Bethesda). 2018;33(1):63–73. https://doi.org/10.1152/physiol.00022.2017</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Touska F, Winter Z, Mueller A, et al. Comprehensive thermal preference phenotyping in mice using a novel automated circular gradient assay. Temperature (Austin). 2016;3(1):77–91. https://doi.org/10.1080/23328940.2015.1135689</mixed-citation><mixed-citation xml:lang="en">Touska F, Winter Z, Mueller A, et al. Comprehensive thermal preference phenotyping in mice using a novel automated circular gradient assay. Temperature (Austin). 2016;3(1):77–91. https://doi.org/10.1080/23328940.2015.1135689</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Hill RZ, Bautista DM. Getting in touch with mechanical pain mechanisms. Trends Neurosci. 2020;43(5):311–25. https://doi.org/10.1016/j.tins.2020.03.004</mixed-citation><mixed-citation xml:lang="en">Hill RZ, Bautista DM. Getting in touch with mechanical pain mechanisms. Trends Neurosci. 2020;43(5):311–25. https://doi.org/10.1016/j.tins.2020.03.004</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Carstens E, Moberg GP. Recognizing pain and distress in laboratory animals. ILAR J. 2000;41(2):62–71. https://doi.org/10.1093/ilar.41.2.62</mixed-citation><mixed-citation xml:lang="en">Carstens E, Moberg GP. Recognizing pain and distress in laboratory animals. ILAR J. 2000;41(2):62–71. https://doi.org/10.1093/ilar.41.2.62</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Costigan M, Woolf CJ. Pain: Molecular mechanisms. J Pain. 2000;1(3 Suppl):35–44. https://doi.org/10.1054/jpai.2000.9818</mixed-citation><mixed-citation xml:lang="en">Costigan M, Woolf CJ. Pain: Molecular mechanisms. J Pain. 2000;1(3 Suppl):35–44. https://doi.org/10.1054/jpai.2000.9818</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Zimmermann K, Hein A, Hager U, et al. Phenotyping sensory nerve endings in vitro in the mouse. Nat Protoc. 2009;4(2):174–96. https://doi.org/10.1038/nprot.2008.223</mixed-citation><mixed-citation xml:lang="en">Zimmermann K, Hein A, Hager U, et al. Phenotyping sensory nerve endings in vitro in the mouse. Nat Protoc. 2009;4(2):174–96. https://doi.org/10.1038/nprot.2008.223</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Cain DM, Khasabov SG, Simone DA. Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study. J Neurophysiol. 2001;85(4):1561–74. https://doi.org/10.1152/jn.2001.85.4.1561</mixed-citation><mixed-citation xml:lang="en">Cain DM, Khasabov SG, Simone DA. Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study. J Neurophysiol. 2001;85(4):1561–74. https://doi.org/10.1152/jn.2001.85.4.1561</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84. https://doi.org/10.1016/j.cell.2009.09.028</mixed-citation><mixed-citation xml:lang="en">Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84. https://doi.org/10.1016/j.cell.2009.09.028</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010;120(11):3760–72. https://doi.org/10.1172/JCI42843</mixed-citation><mixed-citation xml:lang="en">Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010;120(11):3760–72. https://doi.org/10.1172/JCI42843</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Turner PV, Pang DS, Lofgren JL. A review of pain assessment methods in laboratory rodents. Comp Med. 2019;69(6):451–67. https://doi.org/10.30802/aalas-cm-19-000042</mixed-citation><mixed-citation xml:lang="en">Turner PV, Pang DS, Lofgren JL. A review of pain assessment methods in laboratory rodents. Comp Med. 2019;69(6):451–67. https://doi.org/10.30802/aalas-cm-19-000042</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Barrot M. Tests and models of nociception and pain in rodents. Neuroscience. 2012;211:39–50. https://doi.org/10.1016/j.neuroscience.2011.12.041</mixed-citation><mixed-citation xml:lang="en">Barrot M. Tests and models of nociception and pain in rodents. Neuroscience. 2012;211:39–50. https://doi.org/10.1016/j.neuroscience.2011.12.041</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Gårdmark M, Höglund AU, Hammarlund-Udenaes M. Aspects on tail-flick, hot-plate and electrical stimulation tests for morphine antinociception. Pharmacol Toxicol. 1998;83(6):252–8. https://doi.org/10.1111/j.1600-0773.1998.tb01478.x</mixed-citation><mixed-citation xml:lang="en">Gårdmark M, Höglund AU, Hammarlund-Udenaes M. Aspects on tail-flick, hot-plate and electrical stimulation tests for morphine antinociception. Pharmacol Toxicol. 1998;83(6):252–8. https://doi.org/10.1111/j.1600-0773.1998.tb01478.x</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Eschalier A, Marty H, Trolese JF, et al. An automated method to analyze vocalization of unrestrained rats submitted to noxious electrical stimuli. J Pharmacol Methods. 1988;19(2):175–84. https://doi.org/10.1016/0160-5402(88)90038-1</mixed-citation><mixed-citation xml:lang="en">Eschalier A, Marty H, Trolese JF, et al. An automated method to analyze vocalization of unrestrained rats submitted to noxious electrical stimuli. J Pharmacol Methods. 1988;19(2):175–84. https://doi.org/10.1016/0160-5402(88)90038-1</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Sadler KE, Mogil JS, Stucky CL. Innovations and advances in modelling and measuring pain in animals. Nat Rev Neurosci. 2022;23(2):70–85. https://doi.org/10.1038/s41583-021-00536-7</mixed-citation><mixed-citation xml:lang="en">Sadler KE, Mogil JS, Stucky CL. Innovations and advances in modelling and measuring pain in animals. Nat Rev Neurosci. 2022;23(2):70–85. https://doi.org/10.1038/s41583-021-00536-7</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53(1):55–63. https://doi.org/10.1016/0165-0270(94)90144-9</mixed-citation><mixed-citation xml:lang="en">Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53(1):55–63. https://doi.org/10.1016/0165-0270(94)90144-9</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Minett MS, Quick K, Wood JN. Behavioral measures of pain thresholds. Curr Protoc Mouse Biol. 2011;1(3):383–412. https://doi.org/10.1002/9780470942390.mo110116</mixed-citation><mixed-citation xml:lang="en">Minett MS, Quick K, Wood JN. Behavioral measures of pain thresholds. Curr Protoc Mouse Biol. 2011;1(3):383–412. https://doi.org/10.1002/9780470942390.mo110116</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Deuis JR, Dvorakova LS, Vetter I. Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci. 2017;10:284. https://doi.org/10.3389/fnmol.2017.00284</mixed-citation><mixed-citation xml:lang="en">Deuis JR, Dvorakova LS, Vetter I. Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci. 2017;10:284. https://doi.org/10.3389/fnmol.2017.00284</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Callahan BL, Gil ASC, Levesque A, Mogil JS. Modulation of mechanical and thermal nociceptive sensitivity in the laboratory mouse by behavioral state. J Pain. 2008;9(2):174–84. https://doi.org/10.1016/j.jpain.2007.10.011</mixed-citation><mixed-citation xml:lang="en">Callahan BL, Gil ASC, Levesque A, Mogil JS. Modulation of mechanical and thermal nociceptive sensitivity in the laboratory mouse by behavioral state. J Pain. 2008;9(2):174–84. https://doi.org/10.1016/j.jpain.2007.10.011</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Decosterd I, Woolf CJ. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain. 2000;87(2):149–58. https://doi.org/10.1016/S0304-3959(00)00276-1</mixed-citation><mixed-citation xml:lang="en">Decosterd I, Woolf CJ. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain. 2000;87(2):149–58. https://doi.org/10.1016/S0304-3959(00)00276-1</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Nirogi R, Goura V, Shanmuganathan D, et al. Comparison of manual and automated filaments for evaluation of neuropathic pain behavior in rats. J Pharmacol Toxicol Methods. 2012;66(1):8–13. https://doi.org/10.1016/j.vascn.2012.04.006</mixed-citation><mixed-citation xml:lang="en">Nirogi R, Goura V, Shanmuganathan D, et al. Comparison of manual and automated filaments for evaluation of neuropathic pain behavior in rats. J Pharmacol Toxicol Methods. 2012;66(1):8–13. https://doi.org/10.1016/j.vascn.2012.04.006</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Gaffney CM, Muwanga G, Shen H, et al. Mechanical conflict-avoidance assay to measure pain behavior in mice. J Vis Exp. 2022;(180):63454. https://doi.org/10.3791/63454</mixed-citation><mixed-citation xml:lang="en">Gaffney CM, Muwanga G, Shen H, et al. Mechanical conflict-avoidance assay to measure pain behavior in mice. J Vis Exp. 2022;(180):63454. https://doi.org/10.3791/63454</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Harte SE, Meyers JB, Donahue RR, et al. Mechanical conflict system: A novel operant method for the assessment of nociceptive behavior. PLoS One. 2016;11(2):e0150164. https://doi.org/10.1371/journal.pone.0150164</mixed-citation><mixed-citation xml:lang="en">Harte SE, Meyers JB, Donahue RR, et al. Mechanical conflict system: A novel operant method for the assessment of nociceptive behavior. PLoS One. 2016;11(2):e0150164. https://doi.org/10.1371/journal.pone.0150164</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">D’Amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941;72(1):74–9. https://doi.org/10.1016/S0022-3565(25)03823-6</mixed-citation><mixed-citation xml:lang="en">D’Amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941;72(1):74–9. https://doi.org/10.1016/S0022-3565(25)03823-6</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Rossi HL, Neubert JK. Effects of hot and cold stimulus combinations on the thermal preference of rats. Behav Brain Res. 2009;203(2):240–6. https://doi.org/10.1016/j.bbr.2009.05.009</mixed-citation><mixed-citation xml:lang="en">Rossi HL, Neubert JK. Effects of hot and cold stimulus combinations on the thermal preference of rats. Behav Brain Res. 2009;203(2):240–6. https://doi.org/10.1016/j.bbr.2009.05.009</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Jensen TS, Yaksh TL. Comparison of the antinociceptive action of Mu and delta opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique. Brain Res. 1986;372(2):301–12. https://doi.org/10.1016/0006-8993(86)91138-8</mixed-citation><mixed-citation xml:lang="en">Jensen TS, Yaksh TL. Comparison of the antinociceptive action of Mu and delta opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique. Brain Res. 1986;372(2):301–12. https://doi.org/10.1016/0006-8993(86)91138-8</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Bannon AW, Malmberg AB. Models of nociception: Hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci. 2007;Chapter 8:Unit 8.9. https://doi.org/10.1002/0471142301.ns0809s41</mixed-citation><mixed-citation xml:lang="en">Bannon AW, Malmberg AB. Models of nociception: Hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci. 2007;Chapter 8:Unit 8.9. https://doi.org/10.1002/0471142301.ns0809s41</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou Q, Bao Y, Zhang X, et al. Optimal interval for hot water immersion tail-flick test in rats. Acta Neuropsychiatr. 2014;26(4):218–22. https://doi.org/10.1017/neu.2013.57</mixed-citation><mixed-citation xml:lang="en">Zhou Q, Bao Y, Zhang X, et al. Optimal interval for hot water immersion tail-flick test in rats. Acta Neuropsychiatr. 2014;26(4):218–22. https://doi.org/10.1017/neu.2013.57</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Dogrul A, Uzbay TI. Topical clonidine antinociception. J Pain. 2004;111(3):385–91. https://doi.org/10.1016/j.pain.2004.07.020</mixed-citation><mixed-citation xml:lang="en">Dogrul A, Uzbay TI. Topical clonidine antinociception. J Pain. 2004;111(3):385–91. https://doi.org/10.1016/j.pain.2004.07.020</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Yezierski RP, Vierck CJ. Should the hot-plate test be reincarnated? J Pain. 2011;12(8):936–7. https://doi.org/10.1016/j.jpain.2011.05.003</mixed-citation><mixed-citation xml:lang="en">Yezierski RP, Vierck CJ. Should the hot-plate test be reincarnated? J Pain. 2011;12(8):936–7. https://doi.org/10.1016/j.jpain.2011.05.003</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Gunn A, Bobeck EN, Weber C, Morgan MM. The influence of non-nociceptive factors on hot-plate latency in rats. J Pain. 2011;12(2):222–7. https://doi.org/10.1016/j.jpain.2010.06.011</mixed-citation><mixed-citation xml:lang="en">Gunn A, Bobeck EN, Weber C, Morgan MM. The influence of non-nociceptive factors on hot-plate latency in rats. J Pain. 2011;12(2):222–7. https://doi.org/10.1016/j.jpain.2010.06.011</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Espejo EF, Mir D. Differential effects of weekly and daily exposure to the hot plate on the rat’s behavior. Physiol Behav. 1994;55(6):1157–62. https://doi.org/10.1016/0031-9384(94)90404-9</mixed-citation><mixed-citation xml:lang="en">Espejo EF, Mir D. Differential effects of weekly and daily exposure to the hot plate on the rat’s behavior. Physiol Behav. 1994;55(6):1157–62. https://doi.org/10.1016/0031-9384(94)90404-9</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Yalcin I, Charlet A, Freund-Mercier MJ, et al. Differentiating thermal allodynia and hyperalgesia using dynamic hot and cold plate in rodents. J Pain. 2009;10(7):767–73. https://doi.org/10.1016/j.jpain.2009.01.325</mixed-citation><mixed-citation xml:lang="en">Yalcin I, Charlet A, Freund-Mercier MJ, et al. Differentiating thermal allodynia and hyperalgesia using dynamic hot and cold plate in rodents. J Pain. 2009;10(7):767–73. https://doi.org/10.1016/j.jpain.2009.01.325</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Yeomans DC, Pirec V, Proudfit HK. Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: Behavioral evidence. Pain. 1996;68(1):133–40. https://doi.org/10.1016/S0304-3959(96)03176-4</mixed-citation><mixed-citation xml:lang="en">Yeomans DC, Pirec V, Proudfit HK. Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: Behavioral evidence. Pain. 1996;68(1):133–40. https://doi.org/10.1016/S0304-3959(96)03176-4</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Hargreaves K, Dubner R, Brown F, et al. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32(1):77–88. https://doi.org/10.1016/0304-3959(88)90026-7</mixed-citation><mixed-citation xml:lang="en">Hargreaves K, Dubner R, Brown F, et al. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32(1):77–88. https://doi.org/10.1016/0304-3959(88)90026-7</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Balayssac D, Ling B, Ferrier J, et al. Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models. Behav Pharmacol. 2014;25(2):99–111. https://doi.org/10.1097/FBP.0000000000000026</mixed-citation><mixed-citation xml:lang="en">Balayssac D, Ling B, Ferrier J, et al. Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models. Behav Pharmacol. 2014;25(2):99–111. https://doi.org/10.1097/FBP.0000000000000026</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Salte K, Lea G, Franek M, Vaculin S. Baclofen reversed thermal place preference in rats with chronic constriction injury. Physiol Res. 2016;65(2):349–55. https://doi.org/10.33549/physiolres.933008</mixed-citation><mixed-citation xml:lang="en">Salte K, Lea G, Franek M, Vaculin S. Baclofen reversed thermal place preference in rats with chronic constriction injury. Physiol Res. 2016;65(2):349–55. https://doi.org/10.33549/physiolres.933008</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Bourgeois JR, Feustel PJ, Kopec AM. Sex differences in choice-based thermal nociceptive tests in adult rats. Behav Brain Res. 2022;429:113919. https://doi.org/10.1016/j.bbr.2022.113919</mixed-citation><mixed-citation xml:lang="en">Bourgeois JR, Feustel PJ, Kopec AM. Sex differences in choice-based thermal nociceptive tests in adult rats. Behav Brain Res. 2022;429:113919. https://doi.org/10.1016/j.bbr.2022.113919</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Smolinsky AN, Bergner CL, LaPorte JL, Kalueff AV. Analysis of grooming behavior and its utility in studying animal stress, anxiety, and depression. In: Gould TD, ed. Mood and anxiety related phenotypes in mice. Totowa NJ: Humana Press; 2009. https://doi.org/10.1007/978-1-60761-303-9_2</mixed-citation><mixed-citation xml:lang="en">Smolinsky AN, Bergner CL, LaPorte JL, Kalueff AV. Analysis of grooming behavior and its utility in studying animal stress, anxiety, and depression. In: Gould TD, ed. Mood and anxiety related phenotypes in mice. Totowa NJ: Humana Press; 2009. https://doi.org/10.1007/978-1-60761-303-9_2</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Domínguez-Oliva A, Mota-Rojas D, Hernández-Avalos I, et al. The neurobiology of pain and facial movements in rodents: Clinical applications and current research. Front Vet Sci. 2022;9:1016720. https://doi.org/10.3389/fvets.2022.1016720</mixed-citation><mixed-citation xml:lang="en">Domínguez-Oliva A, Mota-Rojas D, Hernández-Avalos I, et al. The neurobiology of pain and facial movements in rodents: Clinical applications and current research. Front Vet Sci. 2022;9:1016720. https://doi.org/10.3389/fvets.2022.1016720</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Tuttle AH, Molinaro MJ, Jethwa JF, et al. A deep neural network to assess spontaneous pain from mouse facial expressions. Mol Pain. 2018;14:1744806918763658. https://doi.org/10.1177/1744806918763658</mixed-citation><mixed-citation xml:lang="en">Tuttle AH, Molinaro MJ, Jethwa JF, et al. A deep neural network to assess spontaneous pain from mouse facial expressions. Mol Pain. 2018;14:1744806918763658. https://doi.org/10.1177/1744806918763658</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Burgdorf JS, Ghoreishi-Haack N, Cearley CN, et al. Rat ultrasonic vocalizations as a measure of the emotional component of chronic pain. Neuroreport. 2019;30(13):863–6. https://doi.org/10.1097/WNR.0000000000001282</mixed-citation><mixed-citation xml:lang="en">Burgdorf JS, Ghoreishi-Haack N, Cearley CN, et al. Rat ultrasonic vocalizations as a measure of the emotional component of chronic pain. Neuroreport. 2019;30(13):863–6. https://doi.org/10.1097/WNR.0000000000001282</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Han JS, Bird GC, Li W, et al. Computerized analysis of audible and ultrasonic vocalizations of rats as a standardized measure of pain-related behavior. J Neurosci Methods. 2005;141(2):261–9. https://doi.org/10.1016/j.jneumeth.2004.07.005</mixed-citation><mixed-citation xml:lang="en">Han JS, Bird GC, Li W, et al. Computerized analysis of audible and ultrasonic vocalizations of rats as a standardized measure of pain-related behavior. J Neurosci Methods. 2005;141(2):261–9. https://doi.org/10.1016/j.jneumeth.2004.07.005</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Wallace VCJ, Norbury TA, Rice ASC. Ultrasound vocalisation by rodents does not correlate with behavioural measures of persistent pain. Eur J Pain. 2005;9(4):445–52. https://doi.org/10.1016/j.ejpain.2004.10.006</mixed-citation><mixed-citation xml:lang="en">Wallace VCJ, Norbury TA, Rice ASC. Ultrasound vocalisation by rodents does not correlate with behavioural measures of persistent pain. Eur J Pain. 2005;9(4):445–52. https://doi.org/10.1016/j.ejpain.2004.10.006</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Lau W, Dykstra C, Thevarkunnel S, Silenieks LB, de Lannoy IAM, Lee DKH. A back translation of pregabaline and carbamazepine against evoked and non-evoked endpoints in the rat spared nerve injury model of neuropatic pain. Neuropharmacology. 2013;73:204–15. https://doi.org/10.1016/j.neuropharm.2013.05.023</mixed-citation><mixed-citation xml:lang="en">Lau W, Dykstra C, Thevarkunnel S, Silenieks LB, de Lannoy IAM, Lee DKH. A back translation of pregabaline and carbamazepine against evoked and non-evoked endpoints in the rat spared nerve injury model of neuropatic pain. Neuropharmacology. 2013;73:204–15. https://doi.org/10.1016/j.neuropharm.2013.05.023</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Jirkof P, Cesarovic N, Rettich A, et al. Burrowing behavior as an indicator of post-laparotomy pain in mice. Front Behav Neurosci. 2010;4:165. https://doi.org/10.3389/fnbeh.2010.00165</mixed-citation><mixed-citation xml:lang="en">Jirkof P, Cesarovic N, Rettich A, et al. Burrowing behavior as an indicator of post-laparotomy pain in mice. Front Behav Neurosci. 2010;4:165. https://doi.org/10.3389/fnbeh.2010.00165</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru">Muralidharan A, Kuo A, Jacob M, et al. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain. Front Behav Neurosci. 2016;10:88. https://doi.org/10.3389/fnbeh.2016.00088</mixed-citation><mixed-citation xml:lang="en">Muralidharan A, Kuo A, Jacob M, et al. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain. Front Behav Neurosci. 2016;10:88. https://doi.org/10.3389/fnbeh.2016.00088</mixed-citation></citation-alternatives></ref><ref id="cit75"><label>75</label><citation-alternatives><mixed-citation xml:lang="ru">van Loo PL, Everse LA, Bernsen MR, et al. Analgesics in mice used in cancer research: Reduction of discomfort? Lab Anim. 1997;31(4):318–25. https://doi.org/10.1258/002367797780596211</mixed-citation><mixed-citation xml:lang="en">van Loo PL, Everse LA, Bernsen MR, et al. Analgesics in mice used in cancer research: Reduction of discomfort? Lab Anim. 1997;31(4):318–25. https://doi.org/10.1258/002367797780596211</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>
