mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2020-1-93-100mrj-999Research ArticleОБЗОРЫREVIEWSМолекулярные аспекты управления ревматической больюRheumatic pain management: molecular aspectsЧетинаЕ. В.ChetinaE. V.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

etchetina@mail.ruШараповаЕ. П.SharapovaE. P.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation20202103202014193100Copyright © Четина Е.В., Шарапова Е.П., 20202020Четина Е.В., Шарапова Е.П.Chetina E.V., Sharapova E.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/999

Ревматические заболевания (РЗ), в том числе остеоартрит и ревматоидный артрит, – это неинфекционные медленно прогрессирующие неизлечимые воспалительные заболевания, приводящие к длительной инвалидности вследствие поражения опорно-двигательного аппарата. Боль является доминирующим симптомом на любой стадии этих заболеваний, непосредственно связана с функционированием суставов и определяет качество жизни больных. При этом, несмотря на значительные успехи в исследовании роли воспаления и регуляции аутоиммунных процессов, патогенетические механизмы развития и сохранения боли при РЗ малоизученны. В развитии ревматической боли участвуют ноцицептивные механизмы, обусловленные воспалением и/или нарушением структуры сустава. Кроме того, ревматическая боль также связана с нарушениями при передаче сигналов нервной системой и психологическими проблемами больных.

На современном этапе лечение боли включает нефармакологические методы, а также использование некоторых фармакологических средств, в частности опиоидов и наркотических средств. Однако, несмотря на значительные успехи в создании препаратов, купирующих боль, в настоящее время у значительной части больных РЗ боль сохраняется и после терапии. При создании новых препаратов для лечения боли необходимо учитывать молекулярные механизмы формирования боли при РЗ. В данном обзоре рассмотрены особенности ее проявлений, молекулярные маркеры и механизмы боли на разных стадиях заболевания у больных двумя наиболее распространенными РЗ – ревматоидным артритом и остеоартритом. 

Rheumatic diseases (RDs), including osteoarthritis and rheumatoid arthritis, are non-infectious slowly progressive incurable inflammatory diseases that lead to prolonged disability due to damage to the musculoskeletal system. Pain is a dominant symptom at any stage of these diseases, is directly related to joint functioning, and determines the quality of life in patients. Moreover, despite the significant successes of studying the role of inflammation and regulation of autoimmune processes, the pathogenetic mechanisms for the development and maintenance of pain in RDs are little investigated. The nociceptive mechanisms due to inflammation and/or joint structural impairment are involved in the development of rheumatic pain. In addition, the latter is also associated with impaired signaling in the nervous system and with psychological problems in patients.

At the present stage, pain treatment includes non-pharmacological interventions, as well as the use of certain pharmacological agents, in particular opioids and narcotic drugs. However, despite significant successes in the design of drugs that relieve pain, at present, a significant proportion of patients with RDs still experience pain after therapy. When designing novel drugs for the treatment of pain, it is necessary to take into account the molecular mechanisms of its development in RDs. This review considers the features of the manifestations of pain, its molecular markers and mechanisms at different stages of the disease in patients with the two most common RDs, such as rheumatoid arthritis and osteoarthritis. 

больмолекулярные маркерыпостоперационная больревматоидный артритостеоартритpainmolecular markerspostoperative painrheumatoid arthritisosteoarthritisReferencesTchetina EV, Semyonova LA. Genetic mechanisms of cartilage degradation in the development and osteoarthritis. In: Protein Purification and Analysis III – Methods and applications; edited by iConcept Press; ISBN 978-1-922227-65-2; iConcept Press Ltd.Tchetina EV, Semyonova LA. Genetic mechanisms of cartilage degradation in the development and osteoarthritis. In: Protein Purification and Analysis III – Methods and applications; edited by iConcept Press; ISBN 978-1-922227-65-2; iConcept Press Ltd.Buckwalter JA, Saltzman C, Brown T. The impact of osteoarthritis: implications for research. Clin Orthop Relat Res. 2004;427(Suppl): S6-15. doi: 10.1097/01.blo.0000143938.30681.9dBuckwalter JA, Saltzman C, Brown T. The impact of osteoarthritis: implications for research. Clin Orthop Relat Res. 2004;427(Suppl): S6-15. doi: 10.1097/01.blo.0000143938.30681.9dDean DD, Azzo W, Martel-Pelletier J, et al. Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest. 1989;84(2): 678-85. doi: 10.1172/JCI114215Dean DD, Azzo W, Martel-Pelletier J, et al. Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest. 1989;84(2): 678-85. doi: 10.1172/JCI114215Muller B. Cytokine imbalance in nonimmunological chronic disease. Cytokine. 2002;18(6):334-9. doi: 10.1006/cyto.2002.0882Muller B. Cytokine imbalance in nonimmunological chronic disease. Cytokine. 2002;18(6):334-9. doi: 10.1006/cyto.2002.0882Aigner T, Rose J, Martin J, Buckwalter J. Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation Res. 2004;7(2):134-45. doi: 10.1089/1549168041552964Aigner T, Rose J, Martin J, Buckwalter J. Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation Res. 2004;7(2):134-45. doi: 10.1089/1549168041552964Lorenzo P, Bayliss MT, Heinegard D. Altered patterns and synthesis of extracellular matrix macromolecules in early osteoarthritis. Matrix Biol. 2004;23(6):381-91. doi: 10.1016/j.matbio.2004.07.007Lorenzo P, Bayliss MT, Heinegard D. Altered patterns and synthesis of extracellular matrix macromolecules in early osteoarthritis. Matrix Biol. 2004;23(6):381-91. doi: 10.1016/j.matbio.2004.07.007Sharif M, Whitehouse A, Sharman P, et al. Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase 3. Arthritis Rheum. 2004;50(2):507-15. doi: 10.1002/art.20020Sharif M, Whitehouse A, Sharman P, et al. Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase 3. Arthritis Rheum. 2004;50(2):507-15. doi: 10.1002/art.20020Clauw DJ, Witter J. Pain and rheumatology: thinking outside the joint. Arthritis Rheum. 2009;60(2):321-4. doi: 10.1002/art.24326Clauw DJ, Witter J. Pain and rheumatology: thinking outside the joint. Arthritis Rheum. 2009;60(2):321-4. doi: 10.1002/art.24326Stoppiello LA, Mapp PI, Wilson D, et al. Structural associations of symptomatic knee osteoarthritis. Arthritis Rheum. 2014;66(11): 3018-27. doi: 10.1002/art.38778Stoppiello LA, Mapp PI, Wilson D, et al. Structural associations of symptomatic knee osteoarthritis. Arthritis Rheum. 2014;66(11): 3018-27. doi: 10.1002/art.38778Poole AR, Guilak F, Abramson SB. Etiopathogenesis of osteoarthritis. In: Moskowitz RW, Altman RD, Hochberg MC, et al, eds. Osteoarthritis: Diagnosis and Medical/ Surgical Management. 4th ed. Lippincott, PA: Williams &Wilkins; 2007. P. 27-49.Poole AR, Guilak F, Abramson SB. Etiopathogenesis of osteoarthritis. In: Moskowitz RW, Altman RD, Hochberg MC, et al, eds. Osteoarthritis: Diagnosis and Medical/ Surgical Management. 4th ed. Lippincott, PA: Williams &Wilkins; 2007. P. 27-49.Sofat N, Ejindu V, Kiely P. What makes osteoarthritis painful? The evidence for local and central pain processing. Rheumatology (Oxford). 2011;50(12):2157-65. doi: 10.1093/rheumatology/ker283Sofat N, Ejindu V, Kiely P. What makes osteoarthritis painful? The evidence for local and central pain processing. Rheumatology (Oxford). 2011;50(12):2157-65. doi: 10.1093/rheumatology/ker283Lee AS, Ellman MB, Yan D, et al. A current review of molecular mechanisms regarding osteoarthritis and pain. Gene. 2013; 527(2):440-7. doi: 10.1016/j.gene. 2013.05.069 13. Saito T. Neurogenic inflammation in osteoarthritis of the knee. Mod Rheumatol. 2003;13(4):301-4. doi: 10.3109/s10165-003-0253-6Lee AS, Ellman MB, Yan D, et al. A current review of molecular mechanisms regarding osteoarthritis and pain. Gene. 2013; 527(2):440-7. doi: 10.1016/j.gene. 2013.05.069 13. Saito T. Neurogenic inflammation in osteoarthritis of the knee. Mod Rheumatol. 2003;13(4):301-4. doi: 10.3109/s10165-003-0253-6Orita S, Ishikawa T, Miyagi M, et al. Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain. BMC Musculoskelet Disord. 2011;12:134. doi: 10.1186/1471-2474-12-134Orita S, Ishikawa T, Miyagi M, et al. Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain. BMC Musculoskelet Disord. 2011;12:134. doi: 10.1186/1471-2474-12-134Moreton BJ, Tew V, das Nair R, et al. Pain phenotype in patients with knee osteoarthritis: classification and measurement properties of painDETECT and self-report Leeds assessment of neuropathic symptoms and signs scale in a cross-sectional study. Arthritis Care Res (Hoboken). 2015;67(4): 519-28. doi: 10.1002/acr.22431Moreton BJ, Tew V, das Nair R, et al. Pain phenotype in patients with knee osteoarthritis: classification and measurement properties of painDETECT and self-report Leeds assessment of neuropathic symptoms and signs scale in a cross-sectional study. Arthritis Care Res (Hoboken). 2015;67(4): 519-28. doi: 10.1002/acr.22431Ordeberg G. Characterization of joint pain in human OA. Novartis Found Symp. 2004;260:105-15; discussion 115-21, 277-9.Ordeberg G. Characterization of joint pain in human OA. Novartis Found Symp. 2004;260:105-15; discussion 115-21, 277-9.Gossec L, Paternotte S, Aanerud GJ, et al. Finalization and validation of the rheumatoid arthritis impact of disease score, a patientderived composite measure of impact of rheumatoid arthritis: a EULAR initiative. Ann Rheum Dis. 2011;70(6): 935-42. doi: 10.1136/ard.2010.142901Gossec L, Paternotte S, Aanerud GJ, et al. Finalization and validation of the rheumatoid arthritis impact of disease score, a patientderived composite measure of impact of rheumatoid arthritis: a EULAR initiative. Ann Rheum Dis. 2011;70(6): 935-42. doi: 10.1136/ard.2010.142901Nijs J, Kosek E, van Oosterwijck J, Meeus M. Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? Pain Physician. 2012;15(3):205-13.Nijs J, Kosek E, van Oosterwijck J, Meeus M. Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? Pain Physician. 2012;15(3):205-13.Daien CI, Hua C, Combe B, Landewe R. Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis. RMD Open. 2017;3(1):e000404. doi: 10.1136/rmdopen2016-000404Daien CI, Hua C, Combe B, Landewe R. Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis. RMD Open. 2017;3(1):e000404. doi: 10.1136/rmdopen2016-000404Ossipov MH. The perception and endogenous modulation of pain. Scientifica (Cairo). 2012;2012:561761. doi: 10.6064/2012/561761Ossipov MH. The perception and endogenous modulation of pain. Scientifica (Cairo). 2012;2012:561761. doi: 10.6064/2012/561761Fitzcharles MA, Shir Y. Management of chronic pain in the rheumatic diseases with insights for the clinician. Ther Adv Musculoskelet Dis. 2011;3(4):179-90. doi: 10.1177/1759720X11408999Fitzcharles MA, Shir Y. Management of chronic pain in the rheumatic diseases with insights for the clinician. Ther Adv Musculoskelet Dis. 2011;3(4):179-90. doi: 10.1177/1759720X11408999Kidd BL, Urban LA. Mechanisms of inflammatory pain. Br J Anaesth. 2001;87(1): 3-11. doi: 10.1093/bja/87.1.3Kidd BL, Urban LA. Mechanisms of inflammatory pain. Br J Anaesth. 2001;87(1): 3-11. doi: 10.1093/bja/87.1.3Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70(18):1630-5. doi: 10.1212/01.wnl.0000282763.29778.59Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70(18):1630-5. doi: 10.1212/01.wnl.0000282763.29778.59Walsh DA, Mapp PI, Kelly S. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation. Br J Clin Pharmacol. 2015;80(5):965-78. doi: 10.1111/bcp.12669Walsh DA, Mapp PI, Kelly S. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation. Br J Clin Pharmacol. 2015;80(5):965-78. doi: 10.1111/bcp.12669Reichling DB, Green PG, Levine JD. The fundamental unit of pain is the cell. Pain. 2013;154(1):S2-9. doi: 10.1016/j.pain.2013.05.037Reichling DB, Green PG, Levine JD. The fundamental unit of pain is the cell. Pain. 2013;154(1):S2-9. doi: 10.1016/j.pain.2013.05.037Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52(1):77-92. doi: 10.1016/j.neuron.2006.09.021Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52(1):77-92. doi: 10.1016/j.neuron.2006.09.021Akinci A, Al Shaker M, Chang MH, et al. Predictive factors and clinical biomarkers for treatment in patients with chronic pain caused by osteoarthritis with a central sensitisation component. Int J Clin Pract. 2016;70(1):31-44. doi: 10.1111/ijcp.12749Akinci A, Al Shaker M, Chang MH, et al. Predictive factors and clinical biomarkers for treatment in patients with chronic pain caused by osteoarthritis with a central sensitisation component. Int J Clin Pract. 2016;70(1):31-44. doi: 10.1111/ijcp.12749Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009; 10(8):895-926. doi: 10.1016/j.jpain.2009.06.012Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009; 10(8):895-926. doi: 10.1016/j.jpain.2009.06.012Nijs J, van Houdenhove B, Oostendorp RA. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Man Ther. 2010;15(2):135-41. doi: 10.1016/j.math.2009.12.001Nijs J, van Houdenhove B, Oostendorp RA. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Man Ther. 2010;15(2):135-41. doi: 10.1016/j.math.2009.12.001Omoigui S. The biochemical origin of pain – proposing a new law of pain: the origin of all pain is inflammation and the inflammatory response. Part 1 of 3-a unifying law of pain. Med Hypotheses. 2007;69(1): 70-82. doi: 10.1016/j.mehy.2006.11.028Omoigui S. The biochemical origin of pain – proposing a new law of pain: the origin of all pain is inflammation and the inflammatory response. Part 1 of 3-a unifying law of pain. Med Hypotheses. 2007;69(1): 70-82. doi: 10.1016/j.mehy.2006.11.028Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med. 2010;16(11):1267-76. doi: 10.1038/nm.2234Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med. 2010;16(11):1267-76. doi: 10.1038/nm.2234Edwards RR, Wasan AD, Bingham CO 3rd, et al. Enhanced reactivity to pain in patients with rheumatoid arthritis. Arthritis Res Ther. 2009;11(3):R61. doi: 10.1186/ar2684Edwards RR, Wasan AD, Bingham CO 3rd, et al. Enhanced reactivity to pain in patients with rheumatoid arthritis. Arthritis Res Ther. 2009;11(3):R61. doi: 10.1186/ar2684Jakobsson U, Hallberg IR. Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthritis: a literature review. J Clin Nurs. 2002;11(4):430-43. doi: 10.1046/j.1365-2702.2002.00624.xJakobsson U, Hallberg IR. Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthritis: a literature review. J Clin Nurs. 2002;11(4):430-43. doi: 10.1046/j.1365-2702.2002.00624.xDavis MC, Zautra AJ, Younger J, et al. Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthritis: implications for fatigue. Brain Behav Immun. 2008;22(1):24-32. doi: 10.1016/j.bbi. 2007.06.013Davis MC, Zautra AJ, Younger J, et al. Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthritis: implications for fatigue. Brain Behav Immun. 2008;22(1):24-32. doi: 10.1016/j.bbi. 2007.06.013Lee YC, Frits ML, Iannaccone CK, et al. Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, and psychosocial factors. Arthritis Rheum. 2014;66(8):2006-14. doi: 10.1002/art.38682Lee YC, Frits ML, Iannaccone CK, et al. Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, and psychosocial factors. Arthritis Rheum. 2014;66(8):2006-14. doi: 10.1002/art.38682Lee YC, Chibnik LB, Lu B, et al. The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2009;11(5):R160. doi: 10.1186/ar2842Lee YC, Chibnik LB, Lu B, et al. The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2009;11(5):R160. doi: 10.1186/ar2842Ranzolin A, Brenol JC, Bredemeier M, et al. Association of concomitant fibromyalgia with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis. Arthritis Rheum. 2009;61(6):794-800. doi: 10.1002/art.24430Ranzolin A, Brenol JC, Bredemeier M, et al. Association of concomitant fibromyalgia with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis. Arthritis Rheum. 2009;61(6):794-800. doi: 10.1002/art.24430Geenen R, van Middendorp H, Bijlsma JW. The impact of stressors on health status and hypothalamic-pituitary-adrenal axis and autonomic nervous system responsiveness in rheumatoid arthritis. Ann N Y Acad Sci. 2006; 1069:77-97. doi: 10.1196/annals.1351.007Geenen R, van Middendorp H, Bijlsma JW. The impact of stressors on health status and hypothalamic-pituitary-adrenal axis and autonomic nervous system responsiveness in rheumatoid arthritis. Ann N Y Acad Sci. 2006; 1069:77-97. doi: 10.1196/annals.1351.007Lee YC, Lu B, Edwards RR, et al. The role of sleep problems in central pain processing in rheumatoid arthritis. Arthritis Rheum. 2013;65(1):59-68. doi: 10.1002/art.37733Lee YC, Lu B, Edwards RR, et al. The role of sleep problems in central pain processing in rheumatoid arthritis. Arthritis Rheum. 2013;65(1):59-68. doi: 10.1002/art.37733Stack RJ, van Tuyl LH, Sloots M, et al. Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development. Rheumatology (Oxford). 2014;53(9):1646-53. doi: 10.1093/rheumatology/keu159Stack RJ, van Tuyl LH, Sloots M, et al. Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development. Rheumatology (Oxford). 2014;53(9):1646-53. doi: 10.1093/rheumatology/keu159Altawil R, Saevarsdottir S, Wedren S, et al. Remaining pain in early rheumatoid arthritis patients treated with methotrexate. Arthritis Care Res (Hoboken). 2016;68(8):1061-8. doi: 10.1002/acr.22790Altawil R, Saevarsdottir S, Wedren S, et al. Remaining pain in early rheumatoid arthritis patients treated with methotrexate. Arthritis Care Res (Hoboken). 2016;68(8):1061-8. doi: 10.1002/acr.22790Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Res Ther. 2011;13(2): 211. doi: 10.1186/ar3306Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Res Ther. 2011;13(2): 211. doi: 10.1186/ar3306Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3):S2-15. doi: 10.1016/j.pain.2010.09.030Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3):S2-15. doi: 10.1016/j.pain.2010.09.030Di Franco M, Guzzo MP, Spinelli FR, et al. Pain and systemic lupus erythematosus. Reumatismo. 2014;66(1):33-8. doi: 10.4081/reumatismo.2014.762Di Franco M, Guzzo MP, Spinelli FR, et al. Pain and systemic lupus erythematosus. Reumatismo. 2014;66(1):33-8. doi: 10.4081/reumatismo.2014.762Malfait AM, Schnitzer TJ. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol. 2013;9(11):654-64. doi: 10.1038/nrrheum.2013.138Malfait AM, Schnitzer TJ. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol. 2013;9(11):654-64. doi: 10.1038/nrrheum.2013.138Zois CD, Katsanos KH, Kosmidou M, Tsianos EV. Neurologic manifestations in inflammatory bowel diseases: current knowledge and novel insights. J Crohns Colitis. 2010;4(2):115-24. doi: 10.1016/j.crohns.2009.10.005Zois CD, Katsanos KH, Kosmidou M, Tsianos EV. Neurologic manifestations in inflammatory bowel diseases: current knowledge and novel insights. J Crohns Colitis. 2010;4(2):115-24. doi: 10.1016/j.crohns.2009.10.005Yunus MB. The prevalence of fibromyalgia in other chronic pain conditions. Pain Res Treat. 2012;2012:584573. doi: 10.1155/2012/584573Yunus MB. The prevalence of fibromyalgia in other chronic pain conditions. Pain Res Treat. 2012;2012:584573. doi: 10.1155/2012/584573Abdelhamid RE, Sluka KA. ASICs mediate pain and inflammation in musculoskeletal diseases. Physiology (Bethesda). 2015;30(6): 449-59. doi: 10.1152/physiol.00030.2015Abdelhamid RE, Sluka KA. ASICs mediate pain and inflammation in musculoskeletal diseases. Physiology (Bethesda). 2015;30(6): 449-59. doi: 10.1152/physiol.00030.2015Westlund KN, Kochukov MY, Lu Y, McNearney TA. Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior. Mol Pain. 2010;6(1):46. doi: 10.1186/1744-8069-6-46Westlund KN, Kochukov MY, Lu Y, McNearney TA. Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior. Mol Pain. 2010;6(1):46. doi: 10.1186/1744-8069-6-46Yamaga M, Tsuji K, Miyatake K, et al. Osteopontin level in synovial fluid is associated with the severity of joint pain and cartilage degradation after anterior cruciate ligament rupture. PLoS One. 2012;7(11):e49014. doi: 10.1371/journal.pone.0049014Yamaga M, Tsuji K, Miyatake K, et al. Osteopontin level in synovial fluid is associated with the severity of joint pain and cartilage degradation after anterior cruciate ligament rupture. PLoS One. 2012;7(11):e49014. doi: 10.1371/journal.pone.0049014Walsh DA, McWilliams DF, Turley MJ, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology (Oxford). 2010;49(10):1852-61. doi: 10.1093/rheumatology/keq188Walsh DA, McWilliams DF, Turley MJ, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology (Oxford). 2010;49(10):1852-61. doi: 10.1093/rheumatology/keq188Barthel C, Yeremenko N, Jacobs R, et al. Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis. Arthritis Res Ther. 2009;11(3):R82. doi: 10.1186/ar2716Barthel C, Yeremenko N, Jacobs R, et al. Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis. Arthritis Res Ther. 2009;11(3):R82. doi: 10.1186/ar2716O’Rourke KP, O’Donoghue G, Adams C, et al. High levels of Lymphotoxin-Beta (LT-Beta) gene expression in rheumatoid arthritis synovium: clinical and cytokine correlations. Rheumatol Int. 2008;28(10):979-86. doi: 10.1007/s00296-008-0574-zO’Rourke KP, O’Donoghue G, Adams C, et al. High levels of Lymphotoxin-Beta (LT-Beta) gene expression in rheumatoid arthritis synovium: clinical and cytokine correlations. Rheumatol Int. 2008;28(10):979-86. doi: 10.1007/s00296-008-0574-zRichardson D, Pearson RG, Kurian N, et al. Characterization of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008;10(2):R43. doi: 10.1186/ar2401Richardson D, Pearson RG, Kurian N, et al. Characterization of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008;10(2):R43. doi: 10.1186/ar2401Mousa SA, Straub RH, Schä fer M, Stein C. Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):871-9. doi: 10.1136/ard.2006.067066Mousa SA, Straub RH, Schä fer M, Stein C. Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):871-9. doi: 10.1136/ard.2006.067066Louati K, Berenbaum F. Fatigue in chronic inflammation – a link to pain pathways. Arthritis Res Ther. 2015;17:254. doi: 10.1186/s13075-015-0784-1Louati K, Berenbaum F. Fatigue in chronic inflammation – a link to pain pathways. Arthritis Res Ther. 2015;17:254. doi: 10.1186/s13075-015-0784-1Clark AK, Staniland AA, Malcangio M. Fractalkine/CX3CR1 signalling in chronic pain and inflammation. Curr Pharm Biotechnol. 2011;12:1707-14. doi: 10.2174/138920111798357465Clark AK, Staniland AA, Malcangio M. Fractalkine/CX3CR1 signalling in chronic pain and inflammation. Curr Pharm Biotechnol. 2011;12:1707-14. doi: 10.2174/138920111798357465Chen YM, Chen HH, Lan JL, Chen DY. Improvement of cognition, a potential benefit of anti-TNF therapy in elderly patients with rheumatoid arthritis. Joint Bone Spine. 2010; 77(4):366-7. doi: 10.1016/j.jbspin.2010.01.017Chen YM, Chen HH, Lan JL, Chen DY. Improvement of cognition, a potential benefit of anti-TNF therapy in elderly patients with rheumatoid arthritis. Joint Bone Spine. 2010; 77(4):366-7. doi: 10.1016/j.jbspin.2010.01.017Clark IA, Vissel B. Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents. J Neuroinflammation. 2016;13(1):236. doi: 10.1186/s12974-016-0708-2Clark IA, Vissel B. Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents. J Neuroinflammation. 2016;13(1):236. doi: 10.1186/s12974-016-0708-2Hess A, Axmann R, Rech J, et al. Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A. 2011;108(9):3731-6. doi: 10.1073/pnas.1011774108Hess A, Axmann R, Rech J, et al. Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A. 2011;108(9):3731-6. doi: 10.1073/pnas.1011774108Kosek E, Altawil R, Kadetoff D, et al. Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain – interleukin-8 in fibromyalgia and interleukin-1β in rheumatoid arthritis. J Neuroimmunol. 2015;280:49-55. doi: 10.1016/j.jneuroim.2015.02.002Kosek E, Altawil R, Kadetoff D, et al. Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain – interleukin-8 in fibromyalgia and interleukin-1β in rheumatoid arthritis. J Neuroimmunol. 2015;280:49-55. doi: 10.1016/j.jneuroim.2015.02.002Lisowska B, Maslinski W, Maldyk P, et al. The role of cytokines in inflammatory response after total knee arthroplasty in patients with rheumatoid arthritis. Rheumatol Int. 2008; 28(7):667-71. doi: 10.1007/s00296-007-0508-1Lisowska B, Maslinski W, Maldyk P, et al. The role of cytokines in inflammatory response after total knee arthroplasty in patients with rheumatoid arthritis. Rheumatol Int. 2008; 28(7):667-71. doi: 10.1007/s00296-007-0508-1Attur MI, Belitskaya-Levy C, Krasnokutsky S, et al. Increased interleukin1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011; 63(7):1908-17. doi: 10.1002/art.30360Attur MI, Belitskaya-Levy C, Krasnokutsky S, et al. Increased interleukin1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011; 63(7):1908-17. doi: 10.1002/art.30360Prochazkova M, Zanvit P, Dolezal T, et al. Increased gene expression and production of spinal cyclooxygenase 1 and 2 during experimental osteoarthritis pain. Physiol Res. 2009; 58(3):419-25.Prochazkova M, Zanvit P, Dolezal T, et al. Increased gene expression and production of spinal cyclooxygenase 1 and 2 during experimental osteoarthritis pain. Physiol Res. 2009; 58(3):419-25.Vardeh D, Wang D, Costigan M, et al. COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice. J Clin Invest. 2009;119(2):287-94. doi: 10.1172/JCI37098Vardeh D, Wang D, Costigan M, et al. COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice. J Clin Invest. 2009;119(2):287-94. doi: 10.1172/JCI37098Leichsenring A, Bä cker I, Wendt W, et al. Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model. BMC Neurosci. 2008;9:80. doi: 10.1186/1471-2202-9-80Leichsenring A, Bä cker I, Wendt W, et al. Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model. BMC Neurosci. 2008;9:80. doi: 10.1186/1471-2202-9-80Kawasaki Y, Xu ZZ, Wang X, et al. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med. 2008;14(3): 331-6. doi: 10.1038/nm1723Kawasaki Y, Xu ZZ, Wang X, et al. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med. 2008;14(3): 331-6. doi: 10.1038/nm1723McDougall JJ, Schuelert N, Bowyer J. Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea pig model of spontaneous osteoarthritis. Osteoarthritis Cartilage. 2010;18(10):1355-7. doi: 10.1016/ j.joca.2010.07.014McDougall JJ, Schuelert N, Bowyer J. Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea pig model of spontaneous osteoarthritis. Osteoarthritis Cartilage. 2010;18(10):1355-7. doi: 10.1016/ j.joca.2010.07.014Ohtori S, Takahashi K, Moriya H, Myers RR. TNF-alpha and TNF-alpha receptor type 1 upregulation in glia and neurons after peripheral nerve injury: studies in murine DRG and spinal cord. Spine (Phila Pa 1976). 2004;29(10):1082-8. doi: 10.1097/00007632-200405150-00006 7Ohtori S, Takahashi K, Moriya H, Myers RR. TNF-alpha and TNF-alpha receptor type 1 upregulation in glia and neurons after peripheral nerve injury: studies in murine DRG and spinal cord. Spine (Phila Pa 1976). 2004;29(10):1082-8. doi: 10.1097/00007632-200405150-00006 7Moon SJ, Woo YJ, Jeong JH, et al. Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes. Osteoarthritis Cartilage. 2012;20(11): 1426-38. doi: 10.1016/j.joca.2012.08.002Moon SJ, Woo YJ, Jeong JH, et al. Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes. Osteoarthritis Cartilage. 2012;20(11): 1426-38. doi: 10.1016/j.joca.2012.08.002Lee J, Hong YS, Jeong JH, et al. Coenzyme Q10 ameliorates pain and cartilage degradation in a rat model of osteoarthritis by regulating nitric oxide and inflammatory cytokines. PLoS One. 2013;8(7):e69362. doi: 10.1371/journal.pone.0069362Lee J, Hong YS, Jeong JH, et al. Coenzyme Q10 ameliorates pain and cartilage degradation in a rat model of osteoarthritis by regulating nitric oxide and inflammatory cytokines. PLoS One. 2013;8(7):e69362. doi: 10.1371/journal.pone.0069362Ji RR, Xu ZZ, Wang X, Lo EH. Matrix metalloprotease regulation of neuropathic pain. Trends Pharmacol Sci. 2009;30(7): 336-40. doi: 10.1016/j.tips.2009.04.002Ji RR, Xu ZZ, Wang X, Lo EH. Matrix metalloprotease regulation of neuropathic pain. Trends Pharmacol Sci. 2009;30(7): 336-40. doi: 10.1016/j.tips.2009.04.002Tejima E, Guo S, Murata Y, et al. Neuroprotective effects of overexpressing tissue inhibitor of metalloproteinase TIMP-1. J Neurotrauma. 2009;26(11):1935-41. doi: 10.1089/neu.2009-0959Tejima E, Guo S, Murata Y, et al. Neuroprotective effects of overexpressing tissue inhibitor of metalloproteinase TIMP-1. J Neurotrauma. 2009;26(11):1935-41. doi: 10.1089/neu.2009-0959Franses RE, McWilliams DF, Mapp PI, Walsh DA. Osteochondral angiogenesis and increased protease inhibitor expression in OA. Osteoarthritis Cartilage. 2010;18(4):563-71. doi: 10.1016/j.joca.2009.11.015Franses RE, McWilliams DF, Mapp PI, Walsh DA. Osteochondral angiogenesis and increased protease inhibitor expression in OA. Osteoarthritis Cartilage. 2010;18(4):563-71. doi: 10.1016/j.joca.2009.11.015Lyu D, Yu W, Tang N, et al. The mTOR signaling pathway regulates pain-related synaptic plasticity in rat entorhinal-hippocampal pathways. Mol Pain. 2013;9:64. doi: 10.1186/1744-8069-9-64Lyu D, Yu W, Tang N, et al. The mTOR signaling pathway regulates pain-related synaptic plasticity in rat entorhinal-hippocampal pathways. Mol Pain. 2013;9:64. doi: 10.1186/1744-8069-9-64Jiang F, Hua LM, Jiao YL, et al. Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator. Neurosci Bull. 2014;30(1):21-32. doi: 10.1007/s12264-013-1377-0Jiang F, Hua LM, Jiao YL, et al. Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator. Neurosci Bull. 2014;30(1):21-32. doi: 10.1007/s12264-013-1377-0Melemedjian OK, Khoutorsky A, Sorge RE, et al. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain. 2013;154(7):1080-91. doi: 10.1016/j.pain.2013.03.021Melemedjian OK, Khoutorsky A, Sorge RE, et al. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain. 2013;154(7):1080-91. doi: 10.1016/j.pain.2013.03.021Geranton SM, Jimenez-Diaz L, Torsney C, et al. A rapamycin-sensitive signaling pathway is essential for the full expression of persistent pain states. J Neurosci. 2009;29(47):15017-27. doi: 10.1523/JNEUROSCI.3451-09.2009Geranton SM, Jimenez-Diaz L, Torsney C, et al. A rapamycin-sensitive signaling pathway is essential for the full expression of persistent pain states. J Neurosci. 2009;29(47):15017-27. doi: 10.1523/JNEUROSCI.3451-09.2009Price TJ, Dussor G. AMPK: An emerging target for modification of injury-induced pain plasticity. Neurosci Lett. 2013;557(Pt A):9-18. doi: 10.1016/j.neulet.2013.06.060Price TJ, Dussor G. AMPK: An emerging target for modification of injury-induced pain plasticity. Neurosci Lett. 2013;557(Pt A):9-18. doi: 10.1016/j.neulet.2013.06.060Blaney Davidson EN, van Caam AP, Vitters EL, et al. TGF-β is a potent inducer of Nerve Growth Factor in articular cartilage via the ALK5-Smad2/3 pathway. Potential role in OA related pain? Osteoarthritis Cartilage. 2015; 23(3):478-86. doi: 10.1016/j.joca.2014.12.005Blaney Davidson EN, van Caam AP, Vitters EL, et al. TGF-β is a potent inducer of Nerve Growth Factor in articular cartilage via the ALK5-Smad2/3 pathway. Potential role in OA related pain? Osteoarthritis Cartilage. 2015; 23(3):478-86. doi: 10.1016/j.joca.2014.12.005Lantero A, Tramullas M, Diaz A, Hurle MA. Transforming growth factor-β in normal nociceptive processing and pathological pain models. Mol Neurobiol. 2012;45(1):76-86. doi: 10.1007/s12035-011-8221-1Lantero A, Tramullas M, Diaz A, Hurle MA. Transforming growth factor-β in normal nociceptive processing and pathological pain models. Mol Neurobiol. 2012;45(1):76-86. doi: 10.1007/s12035-011-8221-1Echeverry S, Shi XQ, Haw A, et al. Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects. Mol Pain. 2009;5:16. doi: 10.1186/1744-8069-5-16Echeverry S, Shi XQ, Haw A, et al. Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects. Mol Pain. 2009;5:16. doi: 10.1186/1744-8069-5-16Christiansen BA, Bhatti S, Goudarzi R, Emami S. Management of Osteoarthritis with Avocado/Soybean Unsaponifiables. Cartilage. 2015;6(1):30-44. doi: 10.1177/1947603514554992Christiansen BA, Bhatti S, Goudarzi R, Emami S. Management of Osteoarthritis with Avocado/Soybean Unsaponifiables. Cartilage. 2015;6(1):30-44. doi: 10.1177/1947603514554992Tramullas M, Lantero A, Diaz A, et al. BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) reveals the involvement of the transforming growth factor-beta family in pain modulation. J Neurosci. 2010;30(4):1502-01. doi: 10.1523/JNEUROSCI.2584-09.2010Tramullas M, Lantero A, Diaz A, et al. BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) reveals the involvement of the transforming growth factor-beta family in pain modulation. J Neurosci. 2010;30(4):1502-01. doi: 10.1523/JNEUROSCI.2584-09.2010Mapp PI, Walsh DA. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol. 2012; 8(7):390-8. doi: 10.1038/nrrheum.2012.80Mapp PI, Walsh DA. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol. 2012; 8(7):390-8. doi: 10.1038/nrrheum.2012.80Brown RA, Weiss JB. Neovascularisation and its role in the osteoarthritic process. Ann Rheum Dis. 1988;47(11):881-5. doi: 10.1136/ard.47.11.881Brown RA, Weiss JB. Neovascularisation and its role in the osteoarthritic process. Ann Rheum Dis. 1988;47(11):881-5. doi: 10.1136/ard.47.11.881Bonnet CS, Walsh DA. Osteoarthritis, angiogenesis and inflammation. Rheumatology (Oxford). 2005;44(1):7-16. doi: 10.1093/ rheumatology/keh344Bonnet CS, Walsh DA. Osteoarthritis, angiogenesis and inflammation. Rheumatology (Oxford). 2005;44(1):7-16. doi: 10.1093/ rheumatology/keh344Ashraf S, Wibberley H, Mapp PI, et al. Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis. Ann Rheum Dis. 2011; 70(3):523-9. doi: 10.1136/ard.2010.137844Ashraf S, Wibberley H, Mapp PI, et al. Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis. Ann Rheum Dis. 2011; 70(3):523-9. doi: 10.1136/ard.2010.137844Walker GD, Fischer M, Gannon J, et al. Expression of type-X collagen in osteoarthritis. J Orthop Res. 1995;13(1):4-12. doi: 10.1002/jor.1100130104Walker GD, Fischer M, Gannon J, et al. Expression of type-X collagen in osteoarthritis. J Orthop Res. 1995;13(1):4-12. doi: 10.1002/jor.1100130104Ballara SC, Miotla JM, Paleolog EM. New vessels, new approaches: angiogenesis as a therapeutic target in musculoskeletal disorders. Int J Exp Pathol. 1999;80(5):235-50. doi: 10.1046/j.1365-2613.1999.00129.xBallara SC, Miotla JM, Paleolog EM. New vessels, new approaches: angiogenesis as a therapeutic target in musculoskeletal disorders. Int J Exp Pathol. 1999;80(5):235-50. doi: 10.1046/j.1365-2613.1999.00129.xKolostova K, Taltynov O, Pinterova D, et al. Tissue repair driven by two different mechanisms of growth factor plasmids VEGF and NGF in mice auricular cartilage: regeneration mediated by administering growth factor plasmids. Eur Arch Otorhinolaryngol. 2012;269(7):1763-70. doi: 10.1007/s00405-011-1821-6Kolostova K, Taltynov O, Pinterova D, et al. Tissue repair driven by two different mechanisms of growth factor plasmids VEGF and NGF in mice auricular cartilage: regeneration mediated by administering growth factor plasmids. Eur Arch Otorhinolaryngol. 2012;269(7):1763-70. doi: 10.1007/s00405-011-1821-6Tchetina EV, Poole AR, Zaitseva EM, et al. Differences in mTOR (mammalian target of rapamycin) gene expression in the peripheral blood and articular cartilages of osteoarthritic patients and disease activity. Arthritis. 2013;2013:461486. doi: 10.1155/2013/461486Tchetina EV, Poole AR, Zaitseva EM, et al. Differences in mTOR (mammalian target of rapamycin) gene expression in the peripheral blood and articular cartilages of osteoarthritic patients and disease activity. Arthritis. 2013;2013:461486. doi: 10.1155/2013/461486Четина ЕВ, Братыгина ЕА, Зайцева ЕМ и др. Прогнозирование течения остеоартроза по экспрессии гена mTOR (mammalian target of rapamycin). Научно-практическая ревматология. 2012;50(1):27-32. doi: 10.14412/1995-4484-2012-500 [Chetina EV, Bratygina EA, Zaitseva EM, et al. Prediction of the course of osteoarthrosis from mTOR (mammalian target of rapamycin) gene expression. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2012;50(1):27-32. doi: 10.14412/1995-4484-2012-500 (In Russ.)].Четина ЕВ, Братыгина ЕА, Зайцева ЕМ и др. Прогнозирование течения остеоартроза по экспрессии гена mTOR (mammalian target of rapamycin). Научно-практическая ревматология. 2012;50(1):27-32. doi: 10.14412/1995-4484-2012-500 [Chetina EV, Bratygina EA, Zaitseva EM, et al. Prediction of the course of osteoarthrosis from mTOR (mammalian target of rapamycin) gene expression. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2012;50(1):27-32. doi: 10.14412/1995-4484-2012-500 (In Russ.)].Четина ЕВ, Маркова ГА, Таскина ЕА и др. Молекулярные механизмы регуляции боли у больных остеоартрозом. Научно-практическая ревматология. 2016; 54(4):424-31. doi: 10.14412/1995-4484-2016-424-431 [Chetina EV, Markova GA, Taskina EA, et al. Molecular mechanisms for pain regulation in patients with osteoarthritis. NauchnoPrakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(4):424-31. doi: 10.14412/1995-4484-2016-424-431 (In Russ.)].Четина ЕВ, Маркова ГА, Таскина ЕА и др. Молекулярные механизмы регуляции боли у больных остеоартрозом. Научно-практическая ревматология. 2016; 54(4):424-31. doi: 10.14412/1995-4484-2016-424-431 [Chetina EV, Markova GA, Taskina EA, et al. Molecular mechanisms for pain regulation in patients with osteoarthritis. NauchnoPrakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(4):424-31. doi: 10.14412/1995-4484-2016-424-431 (In Russ.)].Wolfe F, Michaud K. Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize RA patients with fibromyalgia. J Rheumatol. 2004;31(4):695-700.Wolfe F, Michaud K. Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize RA patients with fibromyalgia. J Rheumatol. 2004;31(4):695-700.Andersson ML, Svensson B, Bergman S. Chronic widespread pain in patients with rheumatoid arthritis and the relation between pain and disease activity measures over the first 5 years. J Rheumatol. 2013;40(12): 1977-85. doi: 10.3899/jrheum.130493Andersson ML, Svensson B, Bergman S. Chronic widespread pain in patients with rheumatoid arthritis and the relation between pain and disease activity measures over the first 5 years. J Rheumatol. 2013;40(12): 1977-85. doi: 10.3899/jrheum.130493Rifbjerg-Madsen S, Christensen AW, Boesen M, et al. Can the painDETECT Questionnaire score and MRI help predict treatment outcome in rheumatoid arthritis: protocol for the Frederiksberg hospital's Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study. BMJ Open. 2014;4(11):e006058. doi: 10.1136/bmjopen-2014-006058Rifbjerg-Madsen S, Christensen AW, Boesen M, et al. Can the painDETECT Questionnaire score and MRI help predict treatment outcome in rheumatoid arthritis: protocol for the Frederiksberg hospital's Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study. BMJ Open. 2014;4(11):e006058. doi: 10.1136/bmjopen-2014-006058Tchetina EV, Pivanova AN, Markova GA, et al. Rituximab down-regulates gene expression associated with cell proliferation, survival, and proteolysis in the peripheral blood from rheumatoid arthritis patients: a link between high baseline autophagy-related ULK1 expression and improved pain control. Arthritis. 2016;2016:4963950. doi: 10.1155/2016/4963950Tchetina EV, Pivanova AN, Markova GA, et al. Rituximab down-regulates gene expression associated with cell proliferation, survival, and proteolysis in the peripheral blood from rheumatoid arthritis patients: a link between high baseline autophagy-related ULK1 expression and improved pain control. Arthritis. 2016;2016:4963950. doi: 10.1155/2016/4963950Orhan CE, Onal A, Ulker S. Antihyperalgesic and antiallodynic effect of sirolimus in neuropathic pain and the role of cytokines in this effect. Neurosci Lett. 2010;481(1):17-20. doi: 10.1016/j.neulet.2010.06.039Orhan CE, Onal A, Ulker S. Antihyperalgesic and antiallodynic effect of sirolimus in neuropathic pain and the role of cytokines in this effect. Neurosci Lett. 2010;481(1):17-20. doi: 10.1016/j.neulet.2010.06.039Yan H, Zhou HF, Hu Y, Pham CT. Suppression of experimental arthritis through AMP-activated protein kinase activation and autophagy modulation. J Rheum Dis Treat. 2015;1(1):5. doi: 10.23937/2469-5726/1510005Yan H, Zhou HF, Hu Y, Pham CT. Suppression of experimental arthritis through AMP-activated protein kinase activation and autophagy modulation. J Rheum Dis Treat. 2015;1(1):5. doi: 10.23937/2469-5726/1510005Kurtz S, Ong K, Lau E, et al. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007; 89(4):780-5. doi: 10.2106/JBJS.F.00222Kurtz S, Ong K, Lau E, et al. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007; 89(4):780-5. doi: 10.2106/JBJS.F.00222Lim AYN, Doherty M. What of guidelines for osteoarthritis? Rheum Dis. 2011; 14:136-44. doi: 10.1111/j.1756-185X.2011.01609.xLim AYN, Doherty M. What of guidelines for osteoarthritis? Rheum Dis. 2011; 14:136-44. doi: 10.1111/j.1756-185X.2011.01609.xHilton ME, Gioe T, Noorbaloochi S, Singh JA. Increasing comorbidity is associated with worsening physical function and pain after primary total knee arthroplasty. BMC Musculoskelet Disord. 2016;17(1):421. doi: 10.1186/s12891-016-1261-yHilton ME, Gioe T, Noorbaloochi S, Singh JA. Increasing comorbidity is associated with worsening physical function and pain after primary total knee arthroplasty. BMC Musculoskelet Disord. 2016;17(1):421. doi: 10.1186/s12891-016-1261-yLiu SS, Buvanendran A, Rathmell JP, et al. Predictors for moderate to severe acute postoperative pain after total hip and knee replacement. Int Orthop. 2012;36(11):2261-7. doi: 10.1007/s00264-012-1623-5Liu SS, Buvanendran A, Rathmell JP, et al. Predictors for moderate to severe acute postoperative pain after total hip and knee replacement. Int Orthop. 2012;36(11):2261-7. doi: 10.1007/s00264-012-1623-5Judge A, Arden NK, Cooper C, et al. Predictors of outcomes of total knee replacement surgery. Rheumatology (Oxford). 2012;51: 1804-13. doi: 10.1093/rheumatology/kes075Judge A, Arden NK, Cooper C, et al. Predictors of outcomes of total knee replacement surgery. Rheumatology (Oxford). 2012;51: 1804-13. doi: 10.1093/rheumatology/kes075Wylde V, Dixon S, Blom AW. The role of preoperative self-efficacy in predicting outcome after total knee replacement. Musculoskeletal Care. 2012;10(2):110-8. doi: 10.1002/msc.1008Wylde V, Dixon S, Blom AW. The role of preoperative self-efficacy in predicting outcome after total knee replacement. Musculoskeletal Care. 2012;10(2):110-8. doi: 10.1002/msc.1008Petersen KK, Arendt-Nielsen L, Simonsen O, et al. Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement. Pain. 2015;156(1):55-61. doi: 10.1016/j.pain.0000000000000022Petersen KK, Arendt-Nielsen L, Simonsen O, et al. Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement. Pain. 2015;156(1):55-61. doi: 10.1016/j.pain.0000000000000022Granot M, Lowenstein L, Yarnitsky D, et al. Postcesarean section pain prediction by preoperative experimental pain assessment. Anesthesiology. 2003;98:1422-6. doi: 10.1097/00000542-200306000-00018Granot M, Lowenstein L, Yarnitsky D, et al. Postcesarean section pain prediction by preoperative experimental pain assessment. Anesthesiology. 2003;98:1422-6. doi: 10.1097/00000542-200306000-00018Edwards RR, Mensing G, Cahalan C, et al. Alteration in pain modulation in women with persistent pain after lumpectomy: influence of catastrophizing. J Pain Symptom Manage. 2013;46:30-42. doi: 10.1016/j.jpainsymman.2012.06.016Edwards RR, Mensing G, Cahalan C, et al. Alteration in pain modulation in women with persistent pain after lumpectomy: influence of catastrophizing. J Pain Symptom Manage. 2013;46:30-42. doi: 10.1016/j.jpainsymman.2012.06.016Yarnitsky D, Crispel Y, Eisenberg E, et al. Prediction of chronic post-operative pain: preoperative DNIC testing identifies patients at risk. Pain. 2008;138:22-8. doi: 10.1016/j.pain.2007.10.033Yarnitsky D, Crispel Y, Eisenberg E, et al. Prediction of chronic post-operative pain: preoperative DNIC testing identifies patients at risk. Pain. 2008;138:22-8. doi: 10.1016/j.pain.2007.10.033Ji RR, Xu ZZ, Gao YJ. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014;13(7):533-48. doi: 10.1038/nrd4334Ji RR, Xu ZZ, Gao YJ. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014;13(7):533-48. doi: 10.1038/nrd4334Pearle A, Scanzello C, George S, et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthr Cartilage. 2007;15:516-23. doi: 10.1016/j.joca.2006.10.010Pearle A, Scanzello C, George S, et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthr Cartilage. 2007;15:516-23. doi: 10.1016/j.joca.2006.10.010Gandhi R, Santone D, Takahashi M, et al. Inflammatory predictors of ongoing pain 2 years following knee replacement surgery. Knee. 2013;20(5):316-8. doi: 10.1016/j.knee.2012.10.015Gandhi R, Santone D, Takahashi M, et al. Inflammatory predictors of ongoing pain 2 years following knee replacement surgery. Knee. 2013;20(5):316-8. doi: 10.1016/j.knee.2012.10.015Clark AK, Yip PK, Grist J, et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci U S A. 2007;104(25):10655-60. doi: 10.1073/pnas.0610811104Clark AK, Yip PK, Grist J, et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci U S A. 2007;104(25):10655-60. doi: 10.1073/pnas.0610811104Clark AK, Yip PK, Malcangio M. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci. 2009;29(21):6945-54. doi: 10.1523/ JNEUROSCI.0828-09.2009Clark AK, Yip PK, Malcangio M. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci. 2009;29(21):6945-54. doi: 10.1523/ JNEUROSCI.0828-09.2009Berta T, Park CK, Xu ZZ, et al. Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-alpha secretion. J Clin Invest. 2014;124(3):1173-86. doi: 10.1172/JCI72230Berta T, Park CK, Xu ZZ, et al. Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-alpha secretion. J Clin Invest. 2014;124(3):1173-86. doi: 10.1172/JCI72230Gardner J, Borgmann K, Deshpande MS, et al. Potential mechanisms for astrocyteTIMP-1 downregulation in chronic inflammatory diseases. J Neurosci Res. 2006;83(7): 1281-92. doi: 10.1002/jnr.20823Gardner J, Borgmann K, Deshpande MS, et al. Potential mechanisms for astrocyteTIMP-1 downregulation in chronic inflammatory diseases. J Neurosci Res. 2006;83(7): 1281-92. doi: 10.1002/jnr.20823Tchetina EV, Makarov SA, Kuzin AN. Coordinated expression of the genes associated with cell growth (mTOR), collagen degradation (cathepsin K), and lipid metabolism (fatty acid synthase) in the peripheral blood and articular cartilage of the end-stage osteoarthritic patients. Ann Rheum Dis. 2013;72(3):694. doi: 10.1136/annrheumdis2013-eular.2051Tchetina EV, Makarov SA, Kuzin AN. Coordinated expression of the genes associated with cell growth (mTOR), collagen degradation (cathepsin K), and lipid metabolism (fatty acid synthase) in the peripheral blood and articular cartilage of the end-stage osteoarthritic patients. Ann Rheum Dis. 2013;72(3):694. doi: 10.1136/annrheumdis2013-eular.2051Tchetina EV, Glemba KE, Markova GA, Makarov SA. Identification of postoperative pain biomarkers using gene expression analyses in the peripheral blood of osteoarthritic patients prior to joint replacement. Ann Rheum Dis. 2019;78(2):A520. doi: 10.1136/annrheumdis-2019-eular.5313Tchetina EV, Glemba KE, Markova GA, Makarov SA. Identification of postoperative pain biomarkers using gene expression analyses in the peripheral blood of osteoarthritic patients prior to joint replacement. Ann Rheum Dis. 2019;78(2):A520. doi: 10.1136/annrheumdis-2019-eular.5313

The authors declare that there are no conflicts of interest present.