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Механизмы развития хронической боли. Подходы к профилактике и лечению
Механизмы развития хронической боли. Подходы к профилактике и лечению
Кукушкин М.Л. Механизмы развития хронической боли. Подходы к профилактике и лечению. Consilium Medicum. 2017; 19 (2): 110–117.
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Аннотация
В работе представлены данные о роли нейробиологических, психологических и социальных факторов в патогенезе хронической боли. Хроническая боль рассматривается не как симптом повреждения тканей, а как самостоятельная болезнь, возникающая вследствие дисфункции систем, осуществляющих регуляцию болевой чувствительности. Сложная патофизиологическая основа хронического болевого синдрома требует комплексного подхода при его лечении с использованием индивидуализированных программ в рамках специализированных противоболевых центров.
Ключевые слова: хроническая боль, периферическая и центральная сенситизация, нейропластичность, профилактика, лечение.
Ключевые слова: хроническая боль, периферическая и центральная сенситизация, нейропластичность, профилактика, лечение.
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Presents data on the role of neurobiological, psychological and social factors in the pathogenesis of chronic pain. Chronic pain is considered not as a symptom of tissue damage, and as an independent disease arising from dysfunction of systems involved in the regulation of pain sensitivity. The complex pathophysiological basis of chronic pain syndrome requires a comprehensive approach in its treatment with the use of individualized programs of specialized pain centers.
Key words: chronic pain, peripheral and central sensitization, neuroplasticity, prevention of pain, treatment of pain.
Key words: chronic pain, peripheral and central sensitization, neuroplasticity, prevention of pain, treatment of pain.
Полный текст
Список литературы
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9. Buskila D, Sarzi-Puttini P, Ablin JN. The genetics of fibromyalgia syndrome. Pharmacogenomic 2007; 8: 67–74.
10. Ceccarelli G et al. Flupirtine: the first Italian experience. Postgrad Med J 1987; 63 (Suppl. 3): 105–8.
11. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms /prepared by International Association for the Study of Pain, Task Force on Taxonomy; editors H.Merskey, N.Bogduk. 2nd ed. Seattle: IASP Press, 1994.
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13. Devulder J. Flupirtine in pain management: pharmacological properties and clinical use. CNS Drugs 2010; 24 (10): 867–81.
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15. Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–73.
16. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386 (9995): 743–800.
17. Harish S et al. Flupirtine: Clinical pharmacology. J Anaesthesiol Clin Pharmacol 2012; 28 (2): 172–7.
18. Inutsuka A, Yamashita A, Chowdhur S et al. The integrative role of orexin/hypocretin neurons in nociceptive perception and analgesic regulation. Scientific Reports 2016; 6: 29480. DOI: 10.1038/srep29480
19. Jetzer AK, Morel A, Magnin M, Jeanmonod D. Cross-modal plasticity in the human thalamus: evidence from intraoperative macrostimulations. Neuroscience 2009; 164: 1867–75.
20. Klinger F, Bajric M, Salzer I et al. Subunit-containing GABAa receptors are preferred targets for the centrally acting analgesic flupirtine. Br J Pharmacol 2015; 172: 4946–58.
21. Lacroix-Fralish ML, Mogil JS. Progress in genetic studies of pain and analgesia. Annu Rev Pharmacol Toxicol 2009; 49: 97–121.
22. Li C, Ni J, Wang Z et al. Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial. Curr Med Res Opin 2008; 24 (12): 3523–30.
23. Mastronardi P et al. Analgesic activity of flupirtine maleate: a controlled double-blind study with diclofenac sodium in orthopaedics. J Int Med Res 1988; 16 (5): 338–48.
24. Ringe JD et al. Analgesic efficacy of flupirtine in primary care of patients with osteoporosis related pain. A multivariate analysis. Arzneimittelforschung 2003; 53 (7): 496–502.
25. Seifert F, Maihöfner C. Functional and structural imaging of pain-induced neuroplasticity. Curr Opin Anaesthesiol 2011; 24: 515–23.
26. Siegmund W et al. Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1. Br J Clin Pharmacol 2015; 79 (3): 501–13. DOI: 10.1111/bcp.12522
27. Thapa D et al. Effect of preoperative flupirtine on postoperative morphine sparing in patients undergoing total abdominal hysterectomy. Saudi J Anaesth 2016; 10 (1): 58–63.
28. Uberall MA, Essner U, Müller-Schwefe GH. 2-week efficacy and tolerability of flupirtine MR and diclofenac in patients with acute low/back pain – results of a post-hoc subgroup analysis of patient-level data from four non-interventional studies. MMW Fortschr Med 2013; 155 (Suppl. 4): 115–23.
29. Uberall MA, Mueller-Schwefe GH, Terhaag B. Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study. Curr Med Res Opin 2012; 28 (10): 1617–34.
30. Wall and Melzack’s Textbook of Pain. 5th Edition. S.B.McMahon, M.Koltzenburg (Eds). Elsevier Churchill Livingstone, 2005.
31. Welsch P, Sommer C, Schiltenwolf M, Häuser W. [Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration]. Schmerz 2015; 29 (1): 85–95. DOI: 10.1007/s00482-014-1436-0
32. Yamamoto T, Nozaki-Taguchi N, Chiba T. Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol 2002; 137: 170–6.
2. Kukushkin M.L., Khitrov N.K. Obshchaia patologiia boli. M.: Meditsina, 2004. [in Russian]
3. Osipov A.V., Kukushkin M.L. Vliianie stressa na razvitie deafferentatsionnogo bolevogo sindroma u krys posle pererezki sedalishchnogo nerva. Biul. eksperimental'noi biologii i meditsiny. 1993; 115 (5): 471–3. [in Russian]
4. Pshennikova M.G., Smirnova V.S., Grafova V.N. i dr. Ustoichivost' k razvitiiu nevropaticheskogo bolevogo sindroma u krys linii avgust i populiatsii vistar, obladaiushchikh raznoi vrozhdennoi ustoichivost'iu k stressovomu vozdeistviiu. Bol'. 2008; 2: 13–6. [in Russian]
5. Bol' (prakticheskoe rukovodstvo dlia vrachei). Pod red. N.N.Iakhno, M.L.Kukushkina. M.: Izd-vo RAMN, 2011. [in Russian]
6. Iakhno N.N., Kukushkin M.L. Khronicheskaia bol': mediko-biologicheskie i sotsial'no-ekonomicheskie aspekty. Vestn. RAMN. 2012; 9: 54–8. [in Russian]
7. Breivik H, Collett B, Ventafridda V et al. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain 2006; 10: 287–333.
8. Buskila D. Genetics of chronic pain states. Best Pract Res Clin Rheumatol 2007; 21: 535–47.
9. Buskila D, Sarzi-Puttini P, Ablin JN. The genetics of fibromyalgia syndrome. Pharmacogenomic 2007; 8: 67–74.
10. Ceccarelli G et al. Flupirtine: the first Italian experience. Postgrad Med J 1987; 63 (Suppl. 3): 105–8.
11. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms /prepared by International Association for the Study of Pain, Task Force on Taxonomy; editors H.Merskey, N.Bogduk. 2nd ed. Seattle: IASP Press, 1994.
12. Diatchenko L, Slade GD, Nackley AG et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 2005; 14 (1): 135–43.
13. Devulder J. Flupirtine in pain management: pharmacological properties and clinical use. CNS Drugs 2010; 24 (10): 867–81.
14. Edwards RR. Genetic predictors of acute and chronic pain. Curr Rheumatol Rep 2006; 8: 411–7.
15. Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–73.
16. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386 (9995): 743–800.
17. Harish S et al. Flupirtine: Clinical pharmacology. J Anaesthesiol Clin Pharmacol 2012; 28 (2): 172–7.
18. Inutsuka A, Yamashita A, Chowdhur S et al. The integrative role of orexin/hypocretin neurons in nociceptive perception and analgesic regulation. Scientific Reports 2016; 6: 29480. DOI: 10.1038/srep29480
19. Jetzer AK, Morel A, Magnin M, Jeanmonod D. Cross-modal plasticity in the human thalamus: evidence from intraoperative macrostimulations. Neuroscience 2009; 164: 1867–75.
20. Klinger F, Bajric M, Salzer I et al. Subunit-containing GABAa receptors are preferred targets for the centrally acting analgesic flupirtine. Br J Pharmacol 2015; 172: 4946–58.
21. Lacroix-Fralish ML, Mogil JS. Progress in genetic studies of pain and analgesia. Annu Rev Pharmacol Toxicol 2009; 49: 97–121.
22. Li C, Ni J, Wang Z et al. Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial. Curr Med Res Opin 2008; 24 (12): 3523–30.
23. Mastronardi P et al. Analgesic activity of flupirtine maleate: a controlled double-blind study with diclofenac sodium in orthopaedics. J Int Med Res 1988; 16 (5): 338–48.
24. Ringe JD et al. Analgesic efficacy of flupirtine in primary care of patients with osteoporosis related pain. A multivariate analysis. Arzneimittelforschung 2003; 53 (7): 496–502.
25. Seifert F, Maihöfner C. Functional and structural imaging of pain-induced neuroplasticity. Curr Opin Anaesthesiol 2011; 24: 515–23.
26. Siegmund W et al. Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1. Br J Clin Pharmacol 2015; 79 (3): 501–13. DOI: 10.1111/bcp.12522
27. Thapa D et al. Effect of preoperative flupirtine on postoperative morphine sparing in patients undergoing total abdominal hysterectomy. Saudi J Anaesth 2016; 10 (1): 58–63.
28. Uberall MA, Essner U, Müller-Schwefe GH. 2-week efficacy and tolerability of flupirtine MR and diclofenac in patients with acute low/back pain – results of a post-hoc subgroup analysis of patient-level data from four non-interventional studies. MMW Fortschr Med 2013; 155 (Suppl. 4): 115–23.
29. Uberall MA, Mueller-Schwefe GH, Terhaag B. Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study. Curr Med Res Opin 2012; 28 (10): 1617–34.
30. Wall and Melzack’s Textbook of Pain. 5th Edition. S.B.McMahon, M.Koltzenburg (Eds). Elsevier Churchill Livingstone, 2005.
31. Welsch P, Sommer C, Schiltenwolf M, Häuser W. [Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration]. Schmerz 2015; 29 (1): 85–95. DOI: 10.1007/s00482-014-1436-0
32. Yamamoto T, Nozaki-Taguchi N, Chiba T. Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol 2002; 137: 170–6.
2. Кукушкин М.Л., Хитров Н.К. Общая патология боли. М.: Медицина, 2004. / Kukushkin M.L., Khitrov N.K. Obshchaia patologiia boli. M.: Meditsina, 2004. [in Russian]
3. Осипов А.В., Кукушкин М.Л. Влияние стресса на развитие деафферентационного болевого синдрома у крыс после перерезки седалищного нерва. Бюл. экспериментальной биологии и медицины. 1993; 115 (5): 471–3. / Osipov A.V., Kukushkin M.L. Vliianie stressa na razvitie deafferentatsionnogo bolevogo sindroma u krys posle pererezki sedalishchnogo nerva. Biul. eksperimental'noi biologii i meditsiny. 1993; 115 (5): 471–3. [in Russian]
4. Пшенникова М.Г., Смирнова В.С., Графова В.Н. и др. Устойчивость к развитию невропатического болевого синдрома у крыс линии август и популяции вистар, обладающих разной врожденной устойчивостью к стрессовому воздействию. Боль. 2008; 2: 13–6. / Pshennikova M.G., Smirnova V.S., Grafova V.N. i dr. Ustoichivost' k razvitiiu nevropaticheskogo bolevogo sindroma u krys linii avgust i populiatsii vistar, obladaiushchikh raznoi vrozhdennoi ustoichivost'iu k stressovomu vozdeistviiu. Bol'. 2008; 2: 13–6. [in Russian]
5. Боль (практическое руководство для врачей). Под ред. Н.Н.Яхно, М.Л.Кукушкина. М.: Изд-во РАМН, 2011. / Bol' (prakticheskoe rukovodstvo dlia vrachei). Pod red. N.N.Iakhno, M.L.Kukushkina. M.: Izd-vo RAMN, 2011. [in Russian]
6. Яхно Н.Н., Кукушкин М.Л. Хроническая боль: медико-биологические и социально-экономические аспекты. Вестн. РАМН. 2012; 9: 54–8. / Iakhno N.N., Kukushkin M.L. Khronicheskaia bol': mediko-biologicheskie i sotsial'no-ekonomicheskie aspekty. Vestn. RAMN. 2012; 9: 54–8. [in Russian]
7. Breivik H, Collett B, Ventafridda V et al. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain 2006; 10: 287–333.
8. Buskila D. Genetics of chronic pain states. Best Pract Res Clin Rheumatol 2007; 21: 535–47.
9. Buskila D, Sarzi-Puttini P, Ablin JN. The genetics of fibromyalgia syndrome. Pharmacogenomic 2007; 8: 67–74.
10. Ceccarelli G et al. Flupirtine: the first Italian experience. Postgrad Med J 1987; 63 (Suppl. 3): 105–8.
11. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms /prepared by International Association for the Study of Pain, Task Force on Taxonomy; editors H.Merskey, N.Bogduk. 2nd ed. Seattle: IASP Press, 1994.
12. Diatchenko L, Slade GD, Nackley AG et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 2005; 14 (1): 135–43.
13. Devulder J. Flupirtine in pain management: pharmacological properties and clinical use. CNS Drugs 2010; 24 (10): 867–81.
14. Edwards RR. Genetic predictors of acute and chronic pain. Curr Rheumatol Rep 2006; 8: 411–7.
15. Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–73.
16. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386 (9995): 743–800.
17. Harish S et al. Flupirtine: Clinical pharmacology. J Anaesthesiol Clin Pharmacol 2012; 28 (2): 172–7.
18. Inutsuka A, Yamashita A, Chowdhur S et al. The integrative role of orexin/hypocretin neurons in nociceptive perception and analgesic regulation. Scientific Reports 2016; 6: 29480. DOI: 10.1038/srep29480
19. Jetzer AK, Morel A, Magnin M, Jeanmonod D. Cross-modal plasticity in the human thalamus: evidence from intraoperative macrostimulations. Neuroscience 2009; 164: 1867–75.
20. Klinger F, Bajric M, Salzer I et al. Subunit-containing GABAa receptors are preferred targets for the centrally acting analgesic flupirtine. Br J Pharmacol 2015; 172: 4946–58.
21. Lacroix-Fralish ML, Mogil JS. Progress in genetic studies of pain and analgesia. Annu Rev Pharmacol Toxicol 2009; 49: 97–121.
22. Li C, Ni J, Wang Z et al. Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial. Curr Med Res Opin 2008; 24 (12): 3523–30.
23. Mastronardi P et al. Analgesic activity of flupirtine maleate: a controlled double-blind study with diclofenac sodium in orthopaedics. J Int Med Res 1988; 16 (5): 338–48.
24. Ringe JD et al. Analgesic efficacy of flupirtine in primary care of patients with osteoporosis related pain. A multivariate analysis. Arzneimittelforschung 2003; 53 (7): 496–502.
25. Seifert F, Maihöfner C. Functional and structural imaging of pain-induced neuroplasticity. Curr Opin Anaesthesiol 2011; 24: 515–23.
26. Siegmund W et al. Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1. Br J Clin Pharmacol 2015; 79 (3): 501–13. DOI: 10.1111/bcp.12522
27. Thapa D et al. Effect of preoperative flupirtine on postoperative morphine sparing in patients undergoing total abdominal hysterectomy. Saudi J Anaesth 2016; 10 (1): 58–63.
28. Uberall MA, Essner U, Müller-Schwefe GH. 2-week efficacy and tolerability of flupirtine MR and diclofenac in patients with acute low/back pain – results of a post-hoc subgroup analysis of patient-level data from four non-interventional studies. MMW Fortschr Med 2013; 155 (Suppl. 4): 115–23.
29. Uberall MA, Mueller-Schwefe GH, Terhaag B. Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study. Curr Med Res Opin 2012; 28 (10): 1617–34.
30. Wall and Melzack’s Textbook of Pain. 5th Edition. S.B.McMahon, M.Koltzenburg (Eds). Elsevier Churchill Livingstone, 2005.
31. Welsch P, Sommer C, Schiltenwolf M, Häuser W. [Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration]. Schmerz 2015; 29 (1): 85–95. DOI: 10.1007/s00482-014-1436-0
32. Yamamoto T, Nozaki-Taguchi N, Chiba T. Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol 2002; 137: 170–6.
________________________________________________
2. Kukushkin M.L., Khitrov N.K. Obshchaia patologiia boli. M.: Meditsina, 2004. [in Russian]
3. Osipov A.V., Kukushkin M.L. Vliianie stressa na razvitie deafferentatsionnogo bolevogo sindroma u krys posle pererezki sedalishchnogo nerva. Biul. eksperimental'noi biologii i meditsiny. 1993; 115 (5): 471–3. [in Russian]
4. Pshennikova M.G., Smirnova V.S., Grafova V.N. i dr. Ustoichivost' k razvitiiu nevropaticheskogo bolevogo sindroma u krys linii avgust i populiatsii vistar, obladaiushchikh raznoi vrozhdennoi ustoichivost'iu k stressovomu vozdeistviiu. Bol'. 2008; 2: 13–6. [in Russian]
5. Bol' (prakticheskoe rukovodstvo dlia vrachei). Pod red. N.N.Iakhno, M.L.Kukushkina. M.: Izd-vo RAMN, 2011. [in Russian]
6. Iakhno N.N., Kukushkin M.L. Khronicheskaia bol': mediko-biologicheskie i sotsial'no-ekonomicheskie aspekty. Vestn. RAMN. 2012; 9: 54–8. [in Russian]
7. Breivik H, Collett B, Ventafridda V et al. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain 2006; 10: 287–333.
8. Buskila D. Genetics of chronic pain states. Best Pract Res Clin Rheumatol 2007; 21: 535–47.
9. Buskila D, Sarzi-Puttini P, Ablin JN. The genetics of fibromyalgia syndrome. Pharmacogenomic 2007; 8: 67–74.
10. Ceccarelli G et al. Flupirtine: the first Italian experience. Postgrad Med J 1987; 63 (Suppl. 3): 105–8.
11. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms /prepared by International Association for the Study of Pain, Task Force on Taxonomy; editors H.Merskey, N.Bogduk. 2nd ed. Seattle: IASP Press, 1994.
12. Diatchenko L, Slade GD, Nackley AG et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 2005; 14 (1): 135–43.
13. Devulder J. Flupirtine in pain management: pharmacological properties and clinical use. CNS Drugs 2010; 24 (10): 867–81.
14. Edwards RR. Genetic predictors of acute and chronic pain. Curr Rheumatol Rep 2006; 8: 411–7.
15. Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–73.
16. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386 (9995): 743–800.
17. Harish S et al. Flupirtine: Clinical pharmacology. J Anaesthesiol Clin Pharmacol 2012; 28 (2): 172–7.
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Авторы
М.Л.Кукушкин
ФГБНУ «Научно-исследовательский институт общей патологии и патофизиологии». 125315, Россия, Москва, ул. Балтийская, д. 8;
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2
mkuk57@gmail.com
ФГБНУ «Научно-исследовательский институт общей патологии и патофизиологии». 125315, Россия, Москва, ул. Балтийская, д. 8;
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2
mkuk57@gmail.com
________________________________________________
M.L.Kukushkin
Research Institute of General Pathology and Pathophysiology. 125315, Russian Federation, Moscow, ul. Baltiiskaia, d. 8;
I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2
mkuk57@gmail.com
Research Institute of General Pathology and Pathophysiology. 125315, Russian Federation, Moscow, ul. Baltiiskaia, d. 8;
I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2
mkuk57@gmail.com
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