Skip to main content
SpringerLink
Log in

Pharmacological Treatment of Pain in Osteoarthritis: A Descriptive Review

  • Osteoarthritis (M Goldring, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Osteoarthritis (OA) is the most common form of arthritis that is characterized by loss of articular cartilage and new formation of bone. Pain and functional disability are common features that lead to disability and poor quality of life. This review discusses the current state of knowledge concerning the treatment of pain in OA, with a focus on pharmacological treatments. This includes the use of non-steroidal anti-inflammatory drugs, acetaminophen, and other disease-modifying agents.

Recent Findings

An updated review of the role of anti-nerve growth factor monoclonal antibodies and other novel agents in the treatment of OA is also presented. In addition, a discussion of current research on biological agents such as small molecules targeting ion channels and G protein-coupled receptors is included. These new pharmacological interventions expand the frontier for treatment of patients with OA.

Summary

The purpose of the review is to provide clinicians with information about the effectiveness of different pharmacological modalities in order to enable them to make the best choices for the treatment of their patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med [Internet]. 2000;133:635–46. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11033593.

  2. Felson DT, Neogi T. Osteoarthritis: is it a disease of cartilage or of bone? Arthritis Rheum. 2004;50:341–4.

    Article  Google Scholar 

  3. Man GS, Mologhianu G. Osteoarthritis pathogenesis—a complex process that involves the entire joint. J Med Life [Internet]. Carol Davila - University Press; 2014;7:37–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24653755.

  4. Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis [Internet]. 2013;5:77–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23641259.

  5. Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman BN, Aliabadi P, et al. The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum [Internet]. 1995;38:1500–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7575700.

  6. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet (Lond, Engl). 2016;388:1545–602.

    Article  Google Scholar 

  7. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58:26–35.

    Article  Google Scholar 

  8. Cisternas MG, Murphy L, Sacks JJ, Solomon DH, Pasta DJ, Helmick CG. Alternative methods for defining osteoarthritis and the impact on estimating prevalence in a US population-based survey. Arthritis Care Res (Hoboken). 2016;68:574–80.

    Article  Google Scholar 

  9. Torio CM, Moore BJ. National inpatient hospital costs: the most expensive conditions by payer, 2013: statistical brief #204. Healthc. Cost Util. Proj. Stat. Briefs. Agency for Healthcare Research and Quality (US); 2006.

  10. • Fu K, Robbins SR, McDougall JJ. Osteoarthritis: the genesis of pain. Rheumatology. 2018;57:iv43–50. This study provides updated information about the mechanism, types, and mediators of pain in OA.

    Article  Google Scholar 

  11. Lluch E, Torres R, Nijs J, Van Oosterwijck J. Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review. Eur J Pain. 2014;18:1367–75.

    Article  CAS  Google Scholar 

  12. McKelvey L, Shorten GD, O’Keeffe GW. Nerve growth factor-mediated regulation of pain signalling and proposed new intervention strategies in clinical pain management. J Neurochem. 2013;124:276–89.

    Article  CAS  Google Scholar 

  13. • Cohen E, Lee YC. A mechanism-based approach to the management of osteoarthritis pain. Curr Osteoporos Rep. 2015;13:399–406. This study provides a clear understanding of the development of pain in OA as well as its management based on the mechanism of the origin of the pain.

    Article  Google Scholar 

  14. Graven-Nielsen T, Wodehouse T, Langford RM, Arendt-Nielsen L, Kidd BL. Normalization of widespread hyperesthesia and facilitated spatial summation of deep-tissue pain in knee osteoarthritis patients after knee replacement. Arthritis Rheum. 2012;64:2907–16.

    Article  CAS  Google Scholar 

  15. Kulkarni B, Bentley DE, Elliott R, Julyan PJ, Boger E, Watson A, et al. Arthritic pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum. 2007;56:1345–54.

    Article  CAS  Google Scholar 

  16. Bhatia D, Bejarano T, Novo M. Current interventions in the management of knee osteoarthritis. J Pharm Bioallied Sci. 2013;5:30–8.

    Article  Google Scholar 

  17. • Geenen R, Overman CL, Christensen R, Åsenlöf P, Capela S, Huisinga KL, et al. EULAR recommendations for the health professional’s approach to pain management in inflammatory arthritis and osteoarthritis. Ann Rheum Dis. 2018;77:797–807. EULAR narrates evidence and expert opinion in order to provide recommendations concerning the management of pain in OA.

    PubMed  Google Scholar 

  18. Anandacoomarasamy A, Caterson I, Sambrook P, Fransen M, March L. The impact of obesity on the musculoskeletal system. Int J Obes. 2008;32:211–22.

    Article  CAS  Google Scholar 

  19. Bennell KL, Hinman RS. A review of the clinical evidence for exercise in osteoarthritis of the hip and knee. J Sci Med Sport. 2011;14:4–9.

    Article  Google Scholar 

  20. Messier SP, Mihalko SL, Legault C, Miller GD, Nicklas BJ, DeVita P, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis. JAMA. 2013;310:1263–73.

    Article  CAS  Google Scholar 

  21. Bliddal H, Leeds AR, Christensen R. Osteoarthritis, obesity and weight loss: evidence, hypotheses and horizons—a scoping review. Obes Rev. 2014;15:578–86.

    Article  CAS  Google Scholar 

  22. Majeed MH, Ali AA, Sudak DM. Mindfulness-based interventions for chronic pain: evidence and applications. Asian J Psychiatr. 2018;32:79–83.

    Article  Google Scholar 

  23. Majeed MH, Sudak DM. Cognitive behavioral therapy for chronic pain-one therapeutic approach for the opioid epidemic. J Psychiatr Pract. 2017;23:409–14.

    PubMed  Google Scholar 

  24. Majeed MH, Ali AA, Sudak DM. Psychotherapeutic interventions for chronic pain: evidence, rationale, and advantages. Int J Psychiatry Med. 2018. https://doi.org/10.1177/009121741879144.

  25. Bjordal JM, Ljunggren AE, Klovning A, Slørdal L. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. BMJ. 2004;329:1317.

    Article  CAS  Google Scholar 

  26. Derry S, Moore RA, Rabbie R. Topical NSAIDs for chronic musculoskeletal pain in adults. In: Derry S, editor. Cochrane database syst rev. Chichester: Wiley; 2012. p. CD007400.

    Google Scholar 

  27. da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet (Lond, Engl). 2017;390:e21–33.

    Article  Google Scholar 

  28. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis. Osteoarthr Cartil [Internet]. 2010;18:476–99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20170770.

  29. Abou-Raya S, Abou-Raya A, Helmii M. Duloxetine for the management of pain in older adults with knee osteoarthritis: randomised placebo-controlled trial. Age Ageing. 2012;41:646–52.

    Article  Google Scholar 

  30. Frakes EP, Risser RC, Ball TD, Hochberg MC, Wohlreich MM. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011;27:2361–72.

    Article  CAS  Google Scholar 

  31. Citrome L, Weiss–Citrome A. A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Postgrad Med. 2012;124:83–93.

    Article  Google Scholar 

  32. Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328:991.

    Article  CAS  Google Scholar 

  33. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971;231:232–5.

    Article  CAS  Google Scholar 

  34. Cashman JN. The mechanisms of action of NSAIDs in analgesia. Drugs [Internet]. 1996;52 Suppl 5:13–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8922554.

  35. Chou R, McDonagh MS, Nakamoto E, Griffin J. Analgesics for osteoarthritis. Analg. Osteoarthr. An Updat. 2006 Comp. Eff. Rev. Agency for Healthcare Research and Quality (US); 2011.

  36. Kienzler J-L, Gold M, Nollevaux F. Systemic bioavailability of topical diclofenac sodium gel 1% versus Oral diclofenac sodium in healthy volunteers. J Clin Pharmacol [Internet]. 2010;50:50–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19841157.

  37. Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15(Suppl 3):S3.

    Article  Google Scholar 

  38. Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26:385–91.

    Article  Google Scholar 

  39. Krijthe BP, Heeringa J, Hofman A, Franco OH, Stricker BH. Non-steroidal anti-inflammatory drugs and the risk of atrial fibrillation: a population-based follow-up study. BMJ Open [Internet]. 2014 [cited 2018 Sep 12];4:e004059. Available from: http://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2013-004059.

  40. Jóźwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm [Internet]. 2014;71:11–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24779190.

  41. Towheed T, Maxwell L, Judd M, Catton M, Hochberg MC, Wells GA. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006;CD004257.

  42. Zhang W, Jones A, Doherty M. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis?: a meta-analysis of randomised controlled trials. Ann Rheum Dis. 2004;63:901–7.

    Article  CAS  Google Scholar 

  43. Jaeschke H. Acetaminophen: dose-dependent drug hepatotoxicity and acute liver failure in patients. Dig Dis. 2015;33:464–71.

    Article  Google Scholar 

  44. Guedes V, Castro JP, Brito I. Topical capsaicin for pain in osteoarthritis: a literature review. Reumatol Clin. 2018;14:40–5.

    Article  Google Scholar 

  45. Dowell D, Haegerich TM, Chou R. CDC Guideline for prescribing opioids for chronic pain—United States, 2016. JAMA [Internet]. 2016 [cited 2017 Jan 17];315:1624. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26977696.

  46. Yi P, Pryzbylkowski P. Opioid induced hyperalgesia. Pain Med. 2015;16(Suppl 1):S32–6.

    Article  Google Scholar 

  47. Brat GA, Agniel D, Beam A, Yorkgitis B, Bicket M, Homer M, et al. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study. BMJ [Internet]. 2018 [cited 2018 Sep 11];j5790. Available from: http://www.bmj.com/lookup/doi/10.1136/bmj.j5790.

  48. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. In: Singh JA, editor. Cochrane database syst rev. Chichester: Wiley; 2015. p. CD005614.

    Google Scholar 

  49. Hochberg MC, Martel-Pelletier J, Monfort J, Möller I, Castillo JR, Arden N, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2016;75:37–44.

    Article  Google Scholar 

  50. Arroll B, Goodyear-Smith F. Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ. 2004;328:869.

    Article  CAS  Google Scholar 

  51. Faúndez J, Cotoras P, Irarrázaval S. Are intraarticular steroids effective for knee osteoarthritis? Medwave. 2016;16:e6599.

    Article  Google Scholar 

  52. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41:356–64.

    Article  Google Scholar 

  53. Cole BJ, Karas V, Hussey K, Merkow DB, Pilz K, Fortier LA. Hyaluronic acid versus platelet-rich plasma: a prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med. 2017;45:339–46.

    Article  Google Scholar 

  54. Karsdal MA, Michaelis M, Ladel C, Siebuhr AS, Bihlet AR, Andersen JR, et al. Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future. Osteoarthr Cartil. 2016;24:2013–21.

    Article  CAS  Google Scholar 

  55. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469–75.

    Article  CAS  Google Scholar 

  56. Fransen M, Agaliotis M, Nairn L, Votrubec M, Bridgett L, Su S, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015;74:851–8.

    Article  CAS  Google Scholar 

  57. Hart LE. In knee OA, intraarticular triamcinolone increased cartilage loss and did not differ from saline for knee pain. Ann Intern Med. 2017;167:JC27.

    Article  Google Scholar 

  58. Wang C-T, Lin J, Chang C-J, Lin Y-T, Hou S-M. Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials. J Bone Joint Surg Am. 2004;86–A:538–45.

    Article  Google Scholar 

  59. Rutjes AWS, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee. Ann Intern Med. 2012;157:180–91.

    Article  Google Scholar 

  60. Anitua E, Sánchez M, Nurden AT, Zalduendo MM, de la Fuente M, Azofra J, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology (Oxford). 2007;46:1769–72.

    Article  CAS  Google Scholar 

  61. Schnitzer TJ, Marks JA. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee. Osteoarthr Cartil. 2015;23:S8–17.

    Article  Google Scholar 

  62. Schnitzer TJ, Ekman EF, Spierings ELH, Greenberg HS, Smith MD, Brown MT, et al. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain. Ann Rheum Dis. 2015;74:1202–11.

    Article  CAS  Google Scholar 

  63. Kan S-L, Li Y, Ning G-Z, Yuan Z-F, Chen L-X, Bi M-C, et al. Tanezumab for patients with osteoarthritis of the knee: a meta-analysis. PLoS One. 2016;11:e0157105.

    Article  Google Scholar 

  64. Tiseo PJ, Kivitz AJ, Ervin JE, Ren H, Mellis SJ. Fasinumab (REGN475), an antibody against nerve growth factor for the treatment of pain: results from a double-blind, placebo-controlled exploratory study in osteoarthritis of the knee. Pain. 2014;155:1245–52.

    Article  CAS  Google Scholar 

  65. Cook AD, Pobjoy J, Steidl S, Dürr M, Braine EL, Turner AL, et al. Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development. Arthritis Res Ther. 2012;14:R199.

    Article  CAS  Google Scholar 

  66. Mullard A. Drug developers reboot anti-NGF pain programmes. Nat Rev Drug Discov. 2015;14:297–8.

    Article  CAS  Google Scholar 

  67. Chen J, Li J, Li R, Wang H, Yang J, Xu J, et al. Efficacy and safety of tanezumab on osteoarthritis knee and hip pains: a meta-analysis of randomized controlled trials. Pain Med. 2016;18:pnw262.

    Article  Google Scholar 

  68. Miller RE, Block JA, Malfait A-M. What is new in pain modification in osteoarthritis? Rheumatology. 2018;57:iv99–iv107.

    Article  Google Scholar 

  69. Emery EC, Luiz AP, Wood JN. Na v 1.7 and other voltage-gated sodium channels as drug targets for pain relief. Expert Opin Ther Targets. 2016;20:975–83.

    Article  CAS  Google Scholar 

  70. Ding H, Kiguchi N, Yasuda D, Daga PR, Polgar WE, Lu JJ, et al. A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates. Sci Transl Med. 2018;10:eaar3483.

    Article  Google Scholar 

Download references

Acknowledgments

Authors have no acknowledgements to report.

Funding

This study was performed independently of any financial support.

Author information

Authors and Affiliations

  1. Division of Psychiatry, Natchaug Hospital, 11 A Stott Ave, Norwich, CT, 06360, USA

    Muhammad Hassan Majeed

  2. Division of Psychiatry, Natchaug Hospital, Norwich, CT, USA

    Syed Ali Amir Sherazi

  3. Department of Anesthesiology, The University of Mississippi Medical Center School of Medicine Jackson, Jackson, MS, 39120, USA

    Douglas Bacon

  4. Boston Headache Institute, and Director, Clinical Research at Boston PainCare, 85 First Ave, Waltham, MA, 02451, USA

    Zahid H. Bajwa

Authors
  1. Muhammad Hassan Majeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syed Ali Amir Sherazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Douglas Bacon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zahid H. Bajwa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammad Hassan Majeed.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Prior Abstract Publication/Presentation

None.

Additional information

This article is part of the Topical Collection on Osteoarthritis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Majeed, M.H., Sherazi, S.A.A., Bacon, D. et al. Pharmacological Treatment of Pain in Osteoarthritis: A Descriptive Review. Curr Rheumatol Rep 20, 88 (2018). https://doi.org/10.1007/s11926-018-0794-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-018-0794-5

Keywords

Search

Navigation