Фармакотерапия хронической боли в спине: есть ли перспективы?

Лечение хронической боли в спине (ХБС) – сложная терапевтическая задача. Гетерогенность патологии, различные фенотипы боли, наличие коморбидных заболеваний и индивидуальная чувствительность к лекарственным препаратам требуют использования широкого спектра обезболивающих средств с разным механизмом действия. 
В настоящем обзоре кратко рассмотрена доказательная база основных фармакологических групп, которые применяются для лечения ХБС в реальной клинической практике или проходят клинические испытания: нестероидные противовоспалительные препараты (НПВП), глюкокортикоиды, ингибиторы фактора некроза опухоли (ФНО) α, ингибиторы фактора роста нервов, опиоиды, антидепрессанты и миорелаксанты, а также антибиотикотерапия. Показано, что в настоящее время даже в перспективе не существует лекарств, применение которых способно полностью решить проблему ХБС. Лечение целесообразно начинать с НПВП. Хотя их эффективность при ХБС относительно невысока, тем не менее использование НПВП позволяет добиться определенного уменьшения боли и создать условия для успешного применения других классов препаратов и немедикаментозных методов. Рассмотрены достоинства нимесулида, который может считаться препаратом первой линии среди НПВП по соотношению эффективности, относительной безопасности и доступности.

1. Knezevic NN, Mandalia S, Raasch J, et al. Treatment of chronic low back pain – new approaches on the horizon. J Pain Res. 2017 May 10;10:1111-1123. doi: 10.2147/JPR.S132769. eCollection 2017.

2. Wong AY, Karppinen J, Samartzis D. Low back pain in older adults: risk factors, management options and future directions. Scoliosis Spinal Disord. 2017 Apr 18;12:14. doi: 10.1186/s13013-017-0121-3. eCollection 2017.

3. Last AR, Hulberta K. Chronic Low Back Pain: Evaluation and Management. Am Fam Physician. 2009;79(12):1067-74.

4. Allegri M, Montella S, Salici F, et al. Mechanisms of low back pain: a guide for diagnosis and therapy. Version 2. F1000Res. 2016 Jun 28 [revised 2016 Oct 11];5. pii: F1000 Faculty Rev-1530. eCollection 2016.

5. Shmagel A, Foley R, Ibrahim H. Epidemiology of Chronic Low Back Pain in US Adults: Data From the 2009-2010 National Health and Nutrition Examination Survey. Arthritis Care Res (Hoboken). 2016 Nov;68(11):1688-94. doi: 10.1002/acr.22890.

6. Deyo R, Mirza S, Turner J, Martin B. Overtreating chronic back pain: time to back off? J Am Board Fam Med. 2009;22(1):62-8.

7. White AP, Arnold PM, Norvell DC, et al. Pharmacologic management of chronic low back pain: synthesis of the evidence. Spine (Phila Pa 1976). 2011 Oct 1;36(21 Suppl):S131-43. doi: 10.1097/BRS.0b013e31822f178f.

8. Chou R, Deyo R, Friedly J, et al. Systemic Pharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2017 Apr 4;166(7):480-492. doi: 10.7326/M16-2458. Epub 2017 Feb 14.

9. Podichetty VK. The aging spine: the role of inflammatory mediators in intervertebral disc degeneration. Cell Mol Biol (Noisy-le-grand). 2007 May 30;53(5):4-18.

10. Peng BG. Pathophysiology, diagnosis, and treatment of discogenic low back pain. World J Orthop. 2013 Apr 18;4(2):42-52. doi: 10.5312/wjo.v4.i2.42. Print 2013 Apr 18.

11. Molinos M, Almeida CR, Caldeira J, et al. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface. 2015 Mar 6;12(104):20141191. doi: 10.1098/rsif.2014.1191.

12. Suri P, Hunter DJ, Rainville J, Guermazi A, Katz JN. Presence and extent of severe facet joint osteoarthritis are associated with back pain in older adults. Osteoarthritis Cartilage. 2013 Sep;21(9):1199-206. doi: 10.1016/j.joca.2013.05.013.

13. Gellhorn AC, Katz JN, Suri P. Osteoarthritis of the spine: the facet joints. Nat Rev Rheumatol. 2013 Apr;9(4):216-24. doi: 10.1038/nrrheum.2012.199. Epub 2012 Nov 13.

14. Modic MT, Steinberg PM, Ross JS, et al. Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology. 1988 Jan;166(1 Pt 1): 193-9.

15. Brinjikji W, Diehn FE, Jarvik JG, et al. MRI Findings of Disc Degeneration are More Prevalent in Adults with Low Back Pain than in Asymptomatic Controls: A Systematic Review and Meta-Analysis. AJNR Am J Neuroradiol. 2015 Dec;36(12):2394-9. doi: 10.3174/ajnr.A4498. Epub 2015 Sep 10.

16. Koes BW, van Tulder M, Lin CW, et al. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J. 2010 Dec;19(12):2075-94. doi: 10.1007/s00586-010-1502-y. Epub 2010 Jul 3.

17. Roelofs PD, Deyo RA, Koes BW, et al. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000396. doi: 10.1002/14651858.CD000396.pub3.

18. Enthoven WTM, Roelofs PD, Koes BW. NSAIDs for Chronic Low Back Pain. JAMA. 2017 Jun 13;317(22):2327-2328. doi: 10.1001/jama.2017.4571.

19. Moore RA, Smugar SS, Wang H, et al. Numbers-needed-to-treat analyses – do timing, dropouts, and outcome matter? Pooled analysis of two randomized, placebo-controlled chronic low back pain trials. Pain. 2010 Dec;151(3):592-7. doi: 10.1016/j.pain.2010.07.013.

20. Kivitz AJ, Gimbel JS, Bramson C, et al. Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain. Pain. 2013 Jul;154(7):1009-21. doi: 10.1016/j.pain.2013.03.006. Epub 2013 Mar 14.

21. Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367. [Epub ahead of print]

22. Scarpignato C, Lanas A, Blandizzi C, et al. Safe prescribing of non-steroidal antiinflammatory drugs in patients with osteoarthritis – an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Med. 2015 Mar 19;13:55. doi: 10.1186/s12916-015-0285-8.

23. McCarberg BH. NSAIDs in the older patient: balancing benefits and harms. Pain Med. 2013 Dec;14 Suppl 1:S43-4. doi: 10.1111/pme.12253

24. Kress HG, Baltov A, Basinski A, et al. Acute pain: a multifaceted challenge – the role of nimesulide. Curr Med Res Opin. 2016;32(1):23-36.

25. Кресс Х, Каратеев АЕ, Кукушкин МЛ. Эффективный контроль боли: научно обоснованные терапевтические подходы. Русский медицинский журнал. 2016;(12): 757-64. [Kress Kh, Karateev AE, Kukushkin ML. Effective pain control: evidence-based therapeutic approaches. Russkii meditsinskii zhurnal. 2016;(12): 757-64. (In Russ.)].

26. Pohjolainen T, Jekunen A, Autio L, Vuorela H. Treatment of acute low back pain with the COX-2-selective anti-inflammatory drug nimesulide: results of a randomized, double-blind comparative trial versus ibuprofen. Spine (Phila Pa 1976). 2000 Jun 15; 25(12):1579-85.

27. Konstantinovic L, Kahjun Z, Milovanovic A, et al. Acute low back pain with radiculopathy: a double – blind, randomized, placebo-controlled study. Photomed Laser Surg. 2010 Aug;28(4):553-60. doi: 10.1089/pho.2009.2576.

28. Mattia C, Ciarcia S, Muhindo A, Coluzzi F. Nimesulide: 25 years later. Minerva Med. 2010 Aug;101(4):285-93.

29. Castellsague J, Pisa F, Rosolen V, et al. Risk of upper gastrointestinal complications in a cohort of users of nimesulide and other nonsteroidal anti-inflammatory drugs in Friuli Venezia Giulia, Italy. Pharmacoepidemiol Drug Saf. 2013 Apr;22(4):365-75.

30. Каратеев АЕ. Российский опыт применения нимесулида: обзор клинических испытаний. Consilium medicum. 2011;13(9):89-95. [Karateev AE. The Russian experience of use of nimesulide: an overview of clinical trials. Consilium medicum. 2011; 13(9):89-95. (In Russ.)].

31. Donati M, Conforti A, Lenti MC, et al. Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug-induced liver injury case-control study in Italy. Br J Clin Pharmacol. 2016 Jul;82(1):238-48. doi: 10.1111/bcp.12938. Epub 2016 Apr 27.

32. Каратеев АЕ, Журавлева МВ. Анализ спонтанных сообщений российских врачей о неблагоприятных реакциях, возникших на фоне приема нимесулида: гепатотоксические осложнения очень редки. Эффективная фармакотерапия. 2015;(8): 4-12. [Karateev AE, Zhuravleva MV. Analysis of spontaneous messages from Russian doctors about the adverse reactions that occurred in patients receiving nimesulide: hepatotoxic complications are very rare. Effektivnaya farmakoterapiya. 2015;(8):4-12. (In Russ.)].

33. Haimovic IC, Beresford HR. Dexamethasone is not superior to placebo for treating lumbosacral radicular pain. Neurology. 1986 Dec;36(12):1593-4.

34. Porsman O, Friis H. Prolapsed lumbar disc treated with intramuscularly administered dexamethasonephosphate. A prospectively planned, double-blind, controlled clinical trial in 52 patients. Scand J Rheumatol. 1979;8(3):142-4.

35. Finckh A, Zufferey P, Schurch MA, et al. Short-term efficacy of intravenous pulse glucocorticoids in acute discogenic sciatica. A randomized controlled trial. Spine (Phila Pa 1976). 2006 Feb 15;31(4):377-81.

36. Friedman BW, Esses D, Solorzano C, et al. A randomized placebo-controlled trial of single-dose IM corticosteroid for radicular low back pain. Spine (Phila Pa 1976). 2008 Aug 15;33(18):E624-9. doi: 10.1097/BRS.0b013e3181822711.

37. Ng L, Chaudhary N, Sell P. The efficacy of corticosteroids in periradicular infiltration for chronic radicular pain: a randomized, double-blind, controlled trial. Spine (Phila Pa 1976). 2005 Apr 15;30(8):857-62.

38. Tafazal S, Ng L, Chaudhary N, Sell P. Corticosteroids in peri-radicular infiltration for radicular pain: a randomised double blind controlled trial. One year results and subgroup analysis. Eur Spine J. 2009 Aug;18(8): 1220-5. doi: 10.1007/s00586-009-1000-2. Epub 2009 Apr 22.

39. Каратеев АЕ. Эпидуральные блокады с использованием глюкокортикоидов: как насчет принципов доказательной медицины? Современная ревматология. 2016;10(3):87–94. [Karateev AE. Epidural blockades using glucocorticoids: As to how the principles of evidence-based medicine? Sovremennaya revmatologiya = Modern Rheumatology Journal. 2016;10(3):87–94. (In Russ.)]. doi: 10.14412/1996-7012-2016-3-87-94

40. Chou R, Hashimoto R, Friedly J, et al. Pain Management Injection Therapies for Low Back Pain [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Mar.

41. Pinto RZ, Maher CG, Ferreira ML, et al. Epidural corticosteroid injections in the management of sciatica: a systematic review and meta-analysis. Ann Intern Med. 2012 Dec 18;157(12):865-77.

42. Staal JB, de Bie RA, de Vet HC, et al. Injection therapy for subacute and chronic low back pain: an updated Cochrane review. Spine (Phila Pa 1976). 2009 Jan 1;34(1):49-59

43. Ter Meulena B, Weinsteina H, Ostelob R, Koehlerd P. The Epidural Treatment of Sciatica: Its Origin and Evolution. Eur Neurol. 2016;75(1-2):58-64. doi: 10.1159/000443729. Epub 2016 Jan 28.

44. Pountos I, Panteli M, Walters G, et al. Safety of Epidural Corticosteroid Injections. Drugs R D. 2016 Mar;16(1):19-34. doi: 10.1007/s40268-015-0119-3.

45. Tobinick E, Davoodifar S. Efficacy of etanercept delivered by perispinal administration for chronic back and/or neck disc-related pain: a study of clinical observations in 143 patients. Curr Med Res Opin. 2004 Jul;20(7): 1075-85.

46. Cohen SP, Wenzell D, Hurley RW, et al. A double-blind, placebo-controlled, doseresponse pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain or lumbosacral radiculopathy. Anesthesiology. 2007 Jul;107(1):99-105.

47. Okoro T, Tafazal SI, Longworth S, Sell PJ. Tumor necrosis alpha-blocking agent (etanercept): a triple blind randomized controlled trial of its use in treatment of sciatica. J Spinal Disord Tech. 2010 Feb;23(1):74-7. doi: 10.1097/BSD.0b013e31819afdc4.

48. Pimentel D, El Abd O, Benyamin R, et al. Anti-tumor necrosis factor antagonists in the treatment of low back pain and radiculopathy: a systematic review and meta-analysis. Pain Physician. 2014 Jan-Feb;17(1):E27-44.

49. Chang DS, Hsu E, Hottinger DG, Cohen SP. Anti-nerve growth factor in pain management: current evidence. J Pain Res. 2016 Jun 8;9:373-83. doi: 10.2147/JPR.S89061. eCollection 2016.

50. Kan SL, Li Y, Ning GZ, et al. Tanezumab for patients with osteoarthritis of the knee: A meta-analysis. PLoS One. 2016 Jun 13;11(6): e0157105. doi: 10.1371/journal.pone.0157105. eCollection 2016.

51. Leite VF, Buehler AM, El Abd O, et al. Anti-nerve growth factor in the treatment of low back pain and radiculopathy: A systematic review and a meta-analysis. Pain Physician. 2014 Jan-Feb;17(1):E45-60.

52. Coluzzi F, Fornasari D, Pergolizzi J, Romualdi P. From acute to chronic pain: tapentadol in the progressive stages of this disease entity. Eur Rev Med Pharmacol Sci. 2017 Apr;21(7):1672-83.

53. Miotto K, Cho AK, Khalil MA, et al. Trends in Tramadol: Pharmacology, Metabolism, and Misuse. Anesth Analg. 2017 Jan;124(1):44-51.

54. Abdel Shaheed C, Maher CG, Williams KA, et al. Efficacy, Tolerability, and Dose- Dependent Effects of Opioid Analgesics for Low Back Pain: A Systematic Review and Meta- analysis. JAMA Intern Med. 2016 Jul 1;176(7):958-68. doi: 10.1001/jamainternmed.2016.1251.

55. Petzke F, Welsch P, Klose P, et al. Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration. Schmerz. 2015 Feb;29(1):60-72. doi: 10.1007/s00482014-1449-8.

56. O'Donnell J, Ekman E, Spalding W, et al. The effectiveness of a weak opioid medication versus a cyclo-oxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug in treating flare-up of chronic low-back pain: results from two randomized, double-blind, 6- week studies. J Int Med Res. 2009 Nov-Dec; 37(6):1789-802.

57. Kremer M, Salvat E, Muller A, et al. Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights. Neuroscience. 2016 Dec 3;338:183-206. doi: 10.1016/j.neuroscience.2016.06.057.Epub 2016 Jul 9.

58. Williamson OD, Sagman D, Bruins RH, et al. Antidepressants in the treatment for chronic low back pain: questioning the validity of meta-analyses. Pain Pract. 2014 Feb;14(2): E33-41. doi: 10.1111/papr.12119. Epub 2013 Oct 17.

59. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014 Jan 3;(1):CD007115. doi: 10.1002/14651858.CD007115.pub3.

60. Brown JP, Boulay LJ. Clinical experience with duloxetine in the management of chronic musculoskeletal pain. A focus on osteoarthritis of the knee. Ther Adv Musculoskelet Dis. 2013 Dec;5(6):291-304. doi: 10.1177/1759720X13508508.

61. Enomoto H, Fujikoshi S, Funai J, et al. Assessment of direct analgesic effect of duloxetine for chronic low back pain: post hoc path analysis of double-blind, placebo- controlled studies. J Pain Res. 2017 Jun 1;10:1357-1368. doi: 10.2147/JPR.S133396. eCollection 2017.

62. Alev L, Fujikoshi S, Yoshikawa A, et al. Duloxetine 60 mg for chronic low back pain: post hoc responder analysis of double-blind, placebo-controlled trials. J Pain Res. 2017 Jul 24;10:1723-1731. doi: 10.2147/JPR.S138297. eCollection 2017.

63. Beebe F, Barkin R, Barkin S. A clinical and pharmacologic review of skeletal muscle relaxants for musculoskeletal conditions. Am J Ther. 2005 Mar-Apr;12(2):151-71.

64. Van Tulder M, Touray T, Furlan A, et al. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003;(2): CD004252.

65. Abdel Shaheed C, Maher CG, Williams KA, McLachlan AJ. Efficacy and tolerability of muscle relaxants for low back pain: Systematic review and meta-analysis. Eur J Pain. 2017 Feb;21(2):228-237. doi: 10.1002/ejp.907. Epub 2016 Jun 22.

66. Friedman BW, Dym AA, Davitt M, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015 Oct 20;314(15): 1572-80. doi: 10.1001/jama.2015.13043.

67. Albert HB, Kjaer P, Jensen TS, et al. Modic changes, possible causes and relation to low back pain. Med Hypotheses. 2008;70(2):361-8. Epub 2007 Jul 10.

68. Stirling A, Worthington T, Rafiq M, et al. Association between sciatica and Propionibacterium acnes. Lancet. 2001 Jun 23;357(9273):2024-5.

69. Ganko R, Rao PJ, Phan K, Mobbs RJ. Can bacterial infection by low virulent organisms be a plausible cause for symptomatic disc degeneration? A systematic review. Spine (Phila Pa 1976). 2015 May 15;40(10):E587-92. doi:10.1097/BRS.0000000000000832.

70. Albert HB, Sorensen JS, Christensen BS, Manniche C. Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double- blind randomized clinical controlled trial of efficacy. Eur Spine J. 2013 Apr;22(4): 697-707. doi: 10.1007/s00586-013-2675-y. Epub 2013 Feb 13.

71. McCartney M. Antibiotics for back pain: hope or hype? BMJ. 2013 May 14;346:f3122. doi: 10.1136/bmj.f3122

72. Chen Z, Cao P, Zhou Z, et al. Overview: the role of Propionibacterium acnes in nonpyogenic intervertebral discs. Int Orthop. 2016 Jun;40(6):1291-8. doi: 10.1007/s00264- 016-3115-5. Epub 2016 Jan 28.

73. Crockett MT, Kelly BS, van Baarsel S, Kavanagh EC. Modic Type 1 Vertebral Endplate Changes: Injury, Inflammation, or Infection? AJR Am J Roentgenol. 2017 Jul;209(1):167-170. doi: 10.2214/AJR.16.17403. Epub 2017 Apr 12.