Chronic pain syndrome management in the elderly: Features, barriers, prospects

The trends of population aging, “rejuvenation” of chronic diseases and their accumulation in the population contribute to the increase in the significance of the problem of pain syndrome, the spread of chronic forms of pain, as well as pain relief issues. Features of therapy of elderly patients with chronic pain syndrome are associated not only with various mechanisms of pain occurrence and regression of physical and functional capabilities of the body associated with the natural aging process, but also with cognitive, emotional status. The most significant barriers in this regard are: low level of compliance and treatment discipline, social isolation, accompanied by the risk of developing mental disorders. To ensure an integrated approach to pain therapy, there is a wide spread of medical prescriptions for non-drug therapy and rehabilitation methods, including physiotherapy and therapeutic physical culture, massage sessions, manual therapy, balneotherapy and therapeutic taping, as well as various forms of psychotherapy that help to better control the symptoms of concomitant diseases and achieve the desired level of compliance. The key component of chronic pain relief is drug therapy. Conventional pharmacological methods of treating noniceptive pain include nonsteroidal anti-inflammatory drugs, analgesic and antipyretic; anticonvulsants and antidepressants are used to treat neuropathic pain. For the optimal choice of a drug for adequate pain relief of the patient, it is necessary to take into account the individual characteristics of the patient (comorbidities and polypharmacy) and use the STOPP/START criteria when prescribing analgesics. The key barrier in the treatment of chronic pain syndrome in the elderly is a significant number of side effects when using existing groups of analgesics. The most significant of them are: hepatotoxicity (paracetamol); the risk of developing aplastic anemia and agranulocytosis (metamizole drugs); gastropathy, hemorrhagic phenomena, increased blood pressure, acute kidney injury (nonsteroidal anti-inflammatory drugs); depression of the respiratory center, risk of addiction and overdose (opioid analgesics). The existing spectrum of adverse events, as well as the growing need for pain relief in older patients and the accumulation of chronic diseases in the population, actualizes the search for more effective and safe alternatives to new drug developments for the scientific medical community.

1. Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161(9):1976–1982. https://doi.org/10.1097/j.pain.0000000000001939.

2. Ovechkin AM. Clinical pathophysiology and anatomy of acute pain. Regional Anesthesia and Acute Pain Management. 2012;6(1):32–40. (In Russ.) Available at: https://elibrary.ru/rpkkur.

3. Legeza VI, Tsygan VN, Drachyov IS, Kudryashov VS, Kondakov AYu. Chronic pain – pathophysiology, clinical characteristics, principles of treatment (current state of the problem). Clinical Pathophysiology. 2023;29(2):20–32. (In Russ.) Available at: https://elibrary.ru/dhtewh.

4. Nicholas M, Vlaeyen JWS, Rief W, Barke A, Aziz Q, Benoliel R et al. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain. 2019;160(1):28–37. https://doi.org/10.1097/j.pain.0000000000001390.

5. Bofanova NS, Masaeva RR, Verbitskaya OS, Koldova TG, Yadrentseva UV. Chronic pain in the 11th revision of the International Classification of Diseases. Russian Journal of Pain. 2021;19(1):36–39. (In Russ.) https://doi.org/10.17116/pain20211901136.

6. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–1858. https://doi.org/10.1016/S0140-6736(18)32279-7.

7. Zimmer Z, Fraser K, Grol-Prokopczyk H, Zajacova A. A global study of pain prevalence across 52 countries: examining the role of country-level contextual factors. Pain. 2022;163(9):1740–1750. https://doi.org/10.1097/j.pain.0000000000002557.

8. Fayaz A, Croft P, Langford RM, Donaldson LJ, Jones GT. Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies. BMJ Open. 2016;6(6):e010364. https://doi.org/10.1136/bmjopen2015-010364.

9. Croft P, Blyth FM, Van der Windt D. The global occurrence of chronic pain: An introduction. In: Chronic Pain Epidemiology. New York: Oxford University Press; 2010. https://doi.org/10.1093/acprof:oso/9780199235766.003.0002.

10. Mäntyselkä PT, Turunen JH, Ahonen RS, Kumpusalo EA. Chronic pain and poor self-rated health. JAMA. 2003;290(18):2435–2442. https://doi.org/10.1001/jama.290.18.2435.

11. Cedraschi C, Ludwig C, Allaz AF, Herrmann FR, Luthy C. Pain and healthrelated quality of life (HRQoL): a national observational study in communitydwelling older adults. Eur Geriatr Med. 2018;9(6):881–889. https://doi.org/10.1007/s41999-018-0114-7.

12. Patel KV, Guralnik JM, Dansie EJ, Turk DC. Prevalence and impact of pain among older adults in the United States: findings from the 2011 National Health and Aging Trends Study. Pain. 2013;154(12):2649–2657. https://doi.org/10.1016/j.pain.2013.07.029.

13. Domenichiello AF, Ramsden CE. The silent epidemic of chronic pain in older adults. Prog Neuropsychopharmacol Biol Psychiatry. 2019;93:284–290. https://doi.org/10.1016/j.pnpbp.2019.04.006.

14. Vorobyeva NM, Manevich TM, Tkacheva ON, Kotovskaya YuV, Selezneva EV, Ovcharova LM. Prevalence and features of chronic pain syndrome in persons over 65 years old: Russian epidemiological study EVKALIPT. Russian Journal of Geriatric Medicine. 2021;(4):425–434. (In Russ.) https://doi.org/10.37586/2686-8636-4-2021-425-434.

15. Churyukanov MV, Davydov OS, Kukushkin ML, Yakhno NN. Prevalence of chronic pain in adult population of the Russian Federation: an allRussian epidemiological study. Russian Journal of Pain. 2025;23(2):54–62. (In Russ.) https://doi.org/10.17116/pain20252302154.

16. Mittendorfer-Rutz E, Dorner TE. Socio-economic factors associated with the 1-year prevalence of severe pain and pain-related sickness absence in the Austrian population. Wien Klin Wochenschr. 2018;130(1-2):4–13. https://doi.org/10.1007/s00508-017-1222-y.

17. Stewart WF, Ricci JA, Chee E, Morganstein D, Lipton R. Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003;290(18):2443–2454. https://doi.org/10.1001/jama.290.18.2443.

18. Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021;397(10289):2082–2097. https://doi.org/10.1016/S0140-6736(21)00393-7.

19. Яхно НН (ред.). Боль. М.: МЕДпресс-информ; 2022. 416 с.

20. Kukushkin ML. Chronic pain: mechanisms of development. Doctor.Ru. 2010;(4):23–28. (In Russ.) Available at: https://elibrary.ru/mtzbjx.

21. Danilov AB. Mixed-type pain. Pathophysiological mechanisms – implications for clinical practice. Approaches to diagnostics and treatment of mixed types of pain syndromes. RMJ. 2014;22(32):10–14. (In Russ.) Available at: https://www.rmj.ru/articles/bolevoy_sindrom/Boly_smeshannogo_tipa_Patofiziologicheskie_mehanizmy__znachenie_dlya_klinicheskoy_praktiki_Podhody_k_diagnostike_i_lecheniyu_smeshannyh_tipov_bolevyh_sindromov/.

22. Whitlock EL, Diaz-Ramirez LG, Glymour MM, Boscardin WJ, Covinsky KE, Smith AK. Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders. JAMA Intern Med. 2017;177(8):1146–1153. https://doi.org/10.1001/jamainternmed.2017.1622.

23. Rouch I, Edjolo A, Laurent B, Dartigues JF, Amieva H. Chronic pain and long-term dementia risk in older adults: Results from a 24-year longitudinal study. Int J Geriatr Psychiatry. 2022;37(5):1–10. https://doi.org/10.1002/gps.5713.

24. Jungquist CR, O’Brien C, Matteson-Rusby S, Smith MT, Pigeon WR, Xia Y et al. The efficacy of cognitive-behavioral therapy for insomnia in patients with chronic pain. Sleep Med. 2010;11(3):302–309. https://doi.org/10.1016/j.sleep.2009.05.018.

25. McCracken LM, Iverson GL. Disrupted sleep patterns and daily functioning in patients with chronic pain. Pain Res Manag. 2002;7(2):75–79. https://doi.org/10.1155/2002/579425.

26. Palermo TM, Law E, Churchill SS, Walker A. Longitudinal course and impact of insomnia symptoms in adolescents with and without chronic pain. J Pain. 2012;13(11):1099–1106. https://doi.org/10.1016/j.jpain.2012.08.003.

27. Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;(4):CD011279. https://doi.org/10.1002/14651858.CD011279.pub3.

28. Wyns A, Hendrix J, Lahousse A, De Bruyne E, Nijs J, Godderis L, Polli A. The Biology of Stress Intolerance in Patients with Chronic Pain-State of the Art and Future Directions. J Clin Med. 2023;12(6):2245. https://doi.org/10.3390/jcm12062245.

29. Kurushina OV, Shkarin VV, Ivasheva VV, Barulin AE. Problems of studying the epidemiology of chronic pain in the Russian Federation. Russian Journal of Pain. 2022;20(3):31–35. (In Russ.) https://doi.org/10.17116/pain20222003131.

30. Smith D, Wilkie R, Uthman O, Jordan JL, McBeth J. Chronic pain and mortality: a systematic review. PLoS ONE. 2014;9(6):e99048. https://doi.org/10.1371/journal.pone.0099048.

31. Naumov AV, Khovasova NO, Polyanskaya AR, Tokareva LG, Tkacheva ON. Chronic pain in elderly and senile patients: clinical recommendations and difficulties in real practice. RMJ. Medical Review. 2023;7(10):680–686. (In Russ.) Available at: https://www.rmj.ru/articles/nevrologiya/Hronicheskaya_boly_u_pacientov_poghilogo_i_starcheskogo_vozrasta_klinicheskie_rekomendacii_i_sloghnosti_realynoy_praktiki/.

32. Ekusheva EV, Komazov AA. Chronic pain in elderly patients. Medical Alphabet. 2021;(3):43–47. (In Russ.) https://doi.org/10.33667/2078-5631-2021-3-43-47.

33. Kaye AD, Baluch A, Scott JT. Pain management in the elderly population: a review. Ochsner J. 2010;10(3):179–187. Available at: https://pubmed.ncbi.nlm.nih.gov/21603375/.

34. Thorlund JB, Simic M, Pihl K, Berthelsen DB, Day R, Koes B, Juhl CB. Similar Effects of Exercise Therapy, Nonsteroidal Anti-inflammatory Drugs, and Opioids for Knee Osteoarthritis Pain: A Systematic Review with Network Meta-analysis. J Orthop Sports Phys Ther. 2022;52(4):207–216. https://doi.org/10.2519/jospt.2022.10490.

35. Bergeron-Vézina K, Corriveau H, Martel M, Harvey MP, Léonard G. Highand low-frequency transcutaneous electrical nerve stimulation does not reduce experimental pain in elderly individuals. Pain. 2015;156(10):2093–2099. https://doi.org/10.1097/j.pain.0000000000000276.

36. Babatunde OO, Jordan JL, Van der Windt DA, Hill JC, Foster NE, Protheroe J. Effective treatment options for musculoskeletal pain in primary care: A systematic overview of current evidence. PLoS ONE. 2017;12(6):e0178621. https://doi.org/10.1371/journal.pone.0178621.

37. Leung DKY, Fong APC, Wong FHC, Liu T, Wong GHY, Lum TYS. Nonpharmacological Interventions for Chronic Pain in Older Adults: A Systematic Review and Meta-Analysis. Gerontologist. 2024;64(6):gnae010. https://doi.org/10.1093/geront/gnae010.

38. Kotovskaya YuV. Safety issues of pain management in geriatric patients. Lechebnoe Delo. 2022;(2):56–61. (In Russ.) https://doi.org/10.24412/2071-5315-2022-12807.

39. Fried TR, Tinetti ME, Iannone L, O’Leary JR, Towle V, Van Ness PH. Health outcome prioritization as a tool for decision making among older persons with multiple chronic conditions. Arch Intern Med. 2011;171(20):1854–1856. https://doi.org/10.1001/archinternmed.2011.424.

40. Herndon CM, Hutchison RW, Berdine HJ, Stacy ZA, Chen JT, Farnsworth DD et al. Management of chronic nonmalignant pain with nonsteroidal antiinflammatory drugs. Joint opinion statement of the Ambulatory Care, Cardiology, and Pain and Palliative Care Practice and Research Networks of the American College of Clinical Pharmacy. Pharmacotherapy. 2008;28(6):788–805. https://doi.org/10.1592/phco.28.6.788.

41. Pasynkova ОО, Krasilnikov AV, Klyushkin IV, Pasynkov DV. Pharmacological treatment of chronic pain in geriatric patients (a review). Bulletin of Contemporary Clinical Medicine. 2019;12(5):81–92. (In Russ.) https://doi.org/10.20969/VSKM.2019.12(5).81-92.

42. Paikova AS, Alexandrov MV, Ushakova SE. Pharmacotherapy options for early and late elderly patients with a risk of falling syndrome. Nervous Diseases. 2019;(2):32–39. (In Russ.) https://doi.org/10.24411/2226-0757-2019-12102.

43. Tkacheva ON, Naumov AV, Kotovskaya YuV, Runikhina NK, Milto AS, Alexanyan LA et al. Chronic pain in older and senile patients. Clinical guidelines. Russian Journal of Geriatric Medicine. 2021;(3):275–320. (In Russ.) https://doi.org/10.37586/2686-8636-3-2021-275-312.

44. O’Mahony D, Cherubini A, Guiteras AR, Denkinger M, Beuscart JB, Onder G et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 3. Eur Geriatr Med. 2023;14(4):625–632. https://doi.org/10.1007/s41999-023-00777-y.

45. Osipova NA, Abuzarova GR, Petrova VV. Principles of the use of analgesics for acute and chronic pain (clinical recommendations). Ambulance Doctor. 2019;(7):54–68. (In Russ.) Available at: https://panor.ru/articles/printsipyprimeneniya-analgeticheskikh-sredstv-pri-ostroy-i-khronicheskoy-boliklinicheskie-rekomendatsii/838.html#.

46. Aweid O, Haider Z, Saed A, Kalairajah Y. Treatment modalities for hip and knee osteoarthritis: A systematic review of safety. J Orthop Surg. 2018;26(3):2309499018808669. https://doi.org/10.1177/2309499018808669.

47. Maher C, Underwood M, Buchbinder R. Non-specific low back pain. Lancet. 2017;389(10070):736–747. https://doi.org/10.1016/S0140-6736(16)30970-9.

48. Zaina F, Côté P, Cancelliere C, Di Felice F, Donzelli S, Rauch A et al. A Systematic Review of Clinical Practice Guidelines for Persons With Nonspecific Low Back Pain With and Without Radiculopathy: Identification of Best Evidence for Rehabilitation to Develop the WHO’s Package of Interventions for Rehabilitation. Arch Phys Med Rehabil. 2023;104(11):1913–1927. https://doi.org/10.1016/j.apmr.2023.02.022.

49. Parfenov VA, Ivanova MA. General practitioners’ management of patients with back pain. Meditsinskiy Sovet. 2018;(1):112–117. (In Russ.) https://doi.org/10.21518/2079-701X-2018-1-112-117.

50. Parfenov VA, Yakhno NN, Davydov OS, Kukushkin ML, Churyukanov MV, Golovacheva VA et al. Chronic nonspecific (musculoskeletal) low back pain. Guidelines of the Russian Society for the Study of Pain (RSSP). Neurology, Neuropsychiatry, Psychosomatics. 2019;11(2S):7–16. (In Russ.) https://doi.org/10.14412/2074-2711-2019-2S-7-16.

51. Golovacheva VA, Golovacheva AA, Golubev VL. Practical guidelines for the treatment of chronic nonspecific low back pain and comorbid chronic insomnia: clinical observation. Meditsinskiy Sovet. 2021;(10):164–170. (In Russ.) https://doi.org/10.21518/2079-701X-2021-10-164-170.

52. Hamid S, Yakoob J, Jafri W, Islam S, Abid S, Islam M. Frequency of NSAID induced peptic ulcer disease. J Pak Med Assoc. 2006;56(5):218–222. Available at: https://pubmed.ncbi.nlm.nih.gov/16767948.

53. Chatterjee S, Dureja GP, Kadhe G, Mane A, Phansalkar AA, Sawant S, Kapatkar V. Cross-Sectional Study for Prevalence of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal, Cardiac and Renal Complications in India: Interim Report. Gastroenterology Res. 2015;8(3-4):216–221. https://doi.org/10.14740/gr658w.

54. Salvo F, Antoniazzi S, Duong M, Molimard M, Bazin F, Fourrier-Réglat A et al. Cardiovascular events associated with the long-term use of NSAIDs: a review of randomized controlled trials and observational studies. Expert Opin Drug Saf. 2014;13(5):573–585. https://doi.org/10.1517/14740338.2014.907792.

55. Ziya Şener Y, Okşul M. Effects of NSAIDs on kidney functions and cardiovascular system. J Clin Hypertens. 2020;22(2):302. https://doi.org/10.1111/jch.13769.

56. Prado NMBL, Messias GC, Santos Junior GO, Nunes VS, Schinonni MI, Paraná R. Prospective monitoring of drug use: drug-induced liver injury in a primary healthcare center. Arq Gastroenterol. 2019;56(4):390–393. https://doi.org/10.1590/S0004-2803.201900000-73.

57. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(4):276–286. https://doi.org/10.7326/M14-2559.

58. Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. 2006;174(11):1589–1594. https://doi.org/10.1503/cmaj.051528.

59. Björnsson ES. Liver injury associated with the analgetic drug metamizole. Br J Clin Pharmacol. 2020;86(7):1248–1250. https://doi.org/10.1111/bcp.14294.

60. Sebode M, Reike-Kunze M, Weidemann S, Zenouzi R, Hartl J, Peiseler M et al. Metamizole: An underrated agent causing severe idiosyncratic druginduced liver injury. Br J Clin Pharmacol. 2020;86(7):1406–1415. https://doi.org/10.1111/bcp.14254.

61. Weber S, Erhardt F, Allgeier J, Saka D, Donga N, Neumann J et al. Drug-Induced Liver Injury Caused by Metamizole: Identification of a Characteristic Injury Pattern. Liver Int. 2025;45(3):e70012. https://doi.org/10.1111/liv.70012.

62. Gaertner J, Stamer UM, Remi C, Voltz R, Bausewein C, Sabatowski R et al. Metamizole/dipyrone for the relief of cancer pain: A systematic review and evidence-based recommendations for clinical practice. Palliat Med. 2017;31(1):26–34. https://doi.org/10.1177/0269216316655746.

63. Pazan F, Weiss C, Wehling M. The FORTA (Fit fOR The Aged) List 2018: Third version of a validated clinical tool for improved drug treatment in older people. Drugs Aging. 2019;36(5):481–484. https://doi.org/10.1007/s40266-019-00669-6.

64. Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial. JAMA. 2017;318(17):1661–1667. https://doi.org/10.1001/jama.2017.16190.

65. Dubgorin AA, Erugina MV, Sazanova GYu, Kagramanyan IN. Assessing the quality of life in patients requiring palliative care at the outpatient stage. Saratov Journal of Medical Scientific Research. 2024;20(4):474–478. (In Russ.) https://doi.org/10.15275/ssmj474.

66. Twycross R, Lickiss N. Pain control and the World Health Organization analgesic ladder. JAMA. 1996;275(11):835–836. https://doi.org/10.1001/jama.275.11.835b.

67. Абузарова ГР, Невзорова ДВ. Обезболивание в паллиативной помощи. М.: Благотворительный фонд помощи хосписам «Вера»; 2018. 60 с. Режим доступа: https://elibrary.ru/xqlqmh.

68. Fallon M, Giusti R, Aielli F, Hoskin P, Rolke R, Sharma M et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(Suppl. 4):iv166–iv191. https://doi.org/10.1093/annonc/mdy152.

69. Yri OE, J A Laird B. Cancer pain – all change please? Clin Med. 2025;25(4):100341. https://doi.org/10.1016/j.clinme.2025.100341.

70. Larkin PJ, Cherny NI, La Carpia D, Guglielmo M, Ostgathe C, Scotté F, Ripamonti CI. Diagnosis, assessment and management of constipation in advanced cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(Suppl. 4):iv111–iv125. https://doi.org/10.1093/annonc/mdy148.

71. Alles SRA, Smith PA. Etiology and Pharmacology of Neuropathic Pain. Pharmacol Rev. 2018;70(2):315–347. https://doi.org/10.1124/pr.117.014399.

72. Russo M, Graham B, Santarelli DM. Gabapentin-Friend or foe? Pain Pract. 2023;23(1):63–69. https://doi.org/10.1111/papr.13165.

73. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173. https://doi.org/10.1016/S1474-4422(14)70251-0.

74. Narayan SW, Naganathan V, Vizza L, Underwood M, Ivers R, McLachlan AJ et al. Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis. Br J Clin Pharmacol. 2024;90(12):3097–3118. https://doi.org/10.1111/bcp.16234.

75. McCoun J, Winkle P, Solanki D, Urban J, Bertoch T, Oswald J et al. Suzetrigine, a Non-Opioid NaV1.8 Inhibitor With Broad Applicability for Moderate-toSevere Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain. J Pain Res. 2025;18:1569–1576. https://doi.org/10.2147/JPR.S509144.

76. Hu S, Lyu D, Gao J. Suzetrigine: The first Nav1.8 inhibitor approved for the treatment of moderate to severe acute pain. Drug Discov Ther. 2025;19(1):80–82. https://doi.org/10.5582/ddt.2025.01010.

77. Osteen JD, Immani S, Tapley TL, Indersmitten T, Hurst NW, Healey T et al. Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective NaV1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain. Pain Ther. 2025;14(2):655–674. https://doi.org/10.1007/s40122-024-00697-0.

78. Zenkova EA, Vdovina GP, Danilova VK, Burlutskaya AA. Toxicity of new compound g-104 – a derivative of isoquinoline and aminohexanoic acid. Russian Journal of Biopharmaceuticals. 2016;8(5):38–43. (In Russ.) Available at: https://submit.biopharmj.ru/ojs238/index.php/biopharmj/article/view/368.

79. Zenkova EA, Vdovina GP, Burlutskaya AA, Danilova VK. Assessment of new nonnarcotic isoquinoline derivative analgesic, compound g-104, for presence of concomitant and unwanted effects typical for analgesics. Perm Medical Journal. 2016;33(1):79–84. (In Russ.) Available at: https://elibrary.ru/voaltt.