Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Overview of the treatment of chronic non-cancer pain

Ellen WK Rosenquist, MD
Section Editor
Mark D Aronson, MD
Deputy Editor
Marianna Crowley, MD


Chronic pain is among the most common reasons for seeking medical attention and is reported by 20 to 50 percent of patients seen in primary care [1,2]. A number of pharmacologic and nonpharmacologic therapies are available for patients with chronic pain. An overview of these treatments is presented here. The evaluation of chronic pain is discussed separately. (See "Evaluation of chronic pain in adults".)

The assessment and management of pain from cancer is discussed separately. (See "Assessment of cancer pain" and "Overview of cancer pain syndromes" and "Cancer pain management: General principles and risk management for patients receiving opioids" and "Cancer pain management with opioids: Optimizing analgesia" and "Cancer pain management: Adjuvant analgesics (coanalgesics)".)


Treatment options for chronic pain generally fall into six major categories: pharmacologic, physical medicine, behavioral medicine, neuromodulation, interventional, and surgical approaches. Optimal patient outcomes often result from multiple approaches utilized in concert, coordinated via a multidisciplinary team [3]. Collaborative care models in primary care can improve pain management and patient outcomes [4,5]. Medication should not be the sole focus of treatment, but should be used when needed, in conjunction with other treatment modalities, to meet treatment goals [6].

Patients with chronic pain require ongoing evaluation, education and reassurance, as well as help in setting reasonable expectations for response. Currently available treatment modalities on average result in only about a 30 percent decrease in pain [7]. But even a partial response of 30 percent can be clinically significant and improve the patient's quality of life [8].


Pharmacologic approaches are the most widely used therapeutic options to ameliorate persistent pain. The major categories of pharmacologic agents for pain management include nonopioid analgesic medications, opioids and adjuvants (used to treat the side effects associated with pain medications or potentiate analgesia):

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Nov 10, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Elliott AM, Smith BH, Penny KI, et al. The epidemiology of chronic pain in the community. Lancet 1999; 354:1248.
  2. Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization Study in Primary Care. JAMA 1998; 280:147.
  3. Kamper SJ, Apeldoorn AT, Chiarotto A, et al. Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and meta-analysis. BMJ 2015; 350:h444.
  4. Dobscha SK, Corson K, Perrin NA, et al. Collaborative care for chronic pain in primary care: a cluster randomized trial. JAMA 2009; 301:1242.
  5. Kroenke K, Krebs EE, Wu J, et al. Telecare collaborative management of chronic pain in primary care: a randomized clinical trial. JAMA 2014; 312:240.
  6. Institute for Clinical Systems Improvement. Health care guideline: Assessment and management of chronic pain. Fourth edition November 2009. http://www.icsi.org/pain__chronic__assessment_and_management_of_14399/pain__chronic__assessment_and_management_of__guideline_.html (Accessed on December 09, 2010).
  7. Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet 2011; 377:2226.
  8. Farrar JT, Young JP Jr, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001; 94:149.
  9. Arnow BA, Hunkeler EM, Blasey CM, et al. Comorbid depression, chronic pain, and disability in primary care. Psychosom Med 2006; 68:262.
  10. World Health Organization. Cancer pain releif. World Health Organization; Geneva, 1990.
  11. Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin Proc 2015; 90:532.
  12. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14:162.
  13. Dworkin RH, O'Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007; 132:237.
  14. McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database Syst Rev 2013; :CD006146.
  15. Freynhagen R, Bennett MI. Diagnosis and management of neuropathic pain. BMJ 2009; 339:b3002.
  16. Attal N, Cruccu G, Haanpää M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol 2006; 13:1153.
  17. Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010; 17:1113.
  18. Moulin DE, Clark AJ, Gilron I, et al. Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag 2007; 12:13.
  19. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011; 76:1758.
  20. O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med 2009; 122:S22.
  21. Zhang W, Doherty M, Leeb BF, et al. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007; 66:377.
  22. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008; 16:137.
  23. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med 2007; 147:478.
  24. Lee C, Straus WL, Balshaw R, et al. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum 2004; 51:746.
  25. Towheed TE, Maxwell L, Judd MG, et al. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006; :CD004257.
  26. Watkins PB, Kaplowitz N, Slattery JT, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 2006; 296:87.
  27. 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.
  28. Fendrick AM, Greenberg BP. A review of the benefits and risks of nonsteroidal anti-inflammatory drugs in the management of mild-to-moderate osteoarthritis. Osteopath Med Prim Care 2009; 3:1.
  29. Von Korff M, Kolodny A, Deyo RA, Chou R. Long-term opioid therapy reconsidered. Ann Intern Med 2011; 155:325.
  30. Smith HS. Potential analgesic mechanisms of acetaminophen. Pain Physician 2009; 12:269.
  31. http://www.fda.gov/drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm (Accessed on May 21, 2014).
  32. Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005; 42:1364.
  33. Jalan R, Williams R, Bernuau J. Paracetamol: are therapeutic doses entirely safe? Lancet 2006; 368:2195.
  34. Temple AR, Lynch JM, Vena J, et al. Aminotransferase activities in healthy subjects receiving three-day dosing of 4, 6, or 8 grams per day of acetaminophen. Clin Toxicol (Phila) 2007; 45:36.
  35. Heard K, Green JL, Bailey JE, et al. A randomized trial to determine the change in alanine aminotransferase during 10 days of paracetamol (acetaminophen) administration in subjects who consume moderate amounts of alcohol. Aliment Pharmacol Ther 2007; 26:283.
  36. García Rodríguez LA, Hernández-Díaz S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 2001; 12:570.
  37. Rahme E, Pettitt D, LeLorier J. Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population. Arthritis Rheum 2002; 46:3046.
  38. http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm239871.htm (Accessed on June 06, 2014).
  39. McCormack K. Non-steroidal anti-inflammatory drugs and spinal nociceptive processing. Pain 1994; 59:9.
  40. Roelofs PD, Deyo RA, Koes BW, et al. Nonsteroidal anti-inflammatory drugs for low back pain: an updated Cochrane review. Spine (Phila Pa 1976) 2008; 33:1766.
  41. National Collaborating Centre for Chronic Conditions (NCCCC). Osteoarthritis: the care and management of osteoarthritis in adults, Royal College of Physicians, London 2008.
  42. American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc 2009; 57:1331.
  43. Altman RD, Dreiser RL, Fisher CL, et al. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. J Rheumatol 2009; 36:1991.
  44. Barthel HR, Haselwood D, Longley S 3rd, et al. Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis. Semin Arthritis Rheum 2009; 39:203.
  45. Simon LS, Grierson LM, Naseer Z, et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009; 143:238.
  46. Jones P, Lamdin R. Oral cyclo-oxygenase 2 inhibitors versus other oral analgesics for acute soft tissue injury: systematic review and meta-analysis. Clin Drug Investig 2010; 30:419.
  47. Antman EM, Bennett JS, Daugherty A, et al. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation 2007; 115:1634.
  48. Cheetham TC, Levy G, Niu F, Bixler F. Gastrointestinal safety of nonsteroidal antiinflammatory drugs and selective cyclooxygenase-2 inhibitors in patients on warfarin. Ann Pharmacother 2009; 43:1765.
  49. Farkouh ME, Greenberg JD, Jeger RV, et al. Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis 2007; 66:764.
  50. Stuart JJ, Pisko EJ. Choline magnesium trisalicylate does not impair platelet aggregation. Pharmatherapeutica 1981; 2:547.
  51. Dobecki DA, Schocket SM, Wallace MS. Update on pharmacotherapy guidelines for the treatment of neuropathic pain. Curr Pain Headache Rep 2006; 10:185.
  52. Finnerup NB, Otto M, Jensen TS, Sindrup SH. An evidence-based algorithm for the treatment of neuropathic pain. MedGenMed 2007; 9:36.
  53. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain 2010; 150:573.
  54. Finnerup NB, Jensen TS. Clinical use of pregabalin in the management of central neuropathic pain. Neuropsychiatr Dis Treat 2007; 3:885.
  55. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2011; :CD007938.
  56. Chou R, Carson S, Chan BK. Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials. J Gen Intern Med 2009; 24:178.
  57. Feng MR, Turluck D, Burleigh J, et al. Brain microdialysis and PK/PD correlation of pregabalin in rats. Eur J Drug Metab Pharmacokinet 2001; 26:123.
  58. Stacey BR, Barrett JA, Whalen E, et al. Pregabalin for postherpetic neuralgia: placebo-controlled trial of fixed and flexible dosing regimens on allodynia and time to onset of pain relief. J Pain 2008; 9:1006.
  59. Moore RA, Straube S, Wiffen PJ, et al. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009; :CD007076.
  60. Silberstein SD, Lipton RB, Dodick DW, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache 2007; 47:170.
  61. Wiffen PJ, Rees J. Lamotrigine for acute and chronic pain. Cochrane Database Syst Rev 2007; :CD006044.
  62. Wiffen PJ, Derry S, Moore RA, Lunn MP. Levetiracetam for neuropathic pain in adults. Cochrane Database Syst Rev 2014; :CD010943.
  63. Gronseth G, Cruccu G, Alksne J, et al. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology 2008; 71:1183.
  64. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database Syst Rev 2011; :CD005451.
  65. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry 2010; 81:1372.
  66. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999; 83:389.
  67. McQuay HJ, Tramèr M, Nye BA, et al. A systematic review of antidepressants in neuropathic pain. Pain 1996; 68:217.
  68. Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol 2005; 96:399.
  69. Collins SL, Moore RA, McQuayHJ, Wiffen P. Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review. J Pain Symptom Manage 2000; 20:449.
  70. Pilowsky I, Hallett EC, Bassett DL, et al. A controlled study of amitriptyline in the treatment of chronic pain. Pain 1982; 14:169.
  71. Jaeschke R, Adachi J, Guyatt G, et al. Clinical usefulness of amitriptyline in fibromyalgia: the results of 23 N-of-1 randomized controlled trials. J Rheumatol 1991; 18:447.
  72. Godfrey RG. A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes. Arch Intern Med 1996; 156:1047.
  73. Finnerup NB, Otto M, McQuay HJ, et al. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005; 118:289.
  74. Aiyer R, Barkin RL, Bhatia A. Treatment of Neuropathic Pain with Venlafaxine: A Systematic Review. Pain Med 2017; 18:1999.
  75. Duloxetine (Cymbalta) for diabetic neuropathic pain. Med Lett Drugs Ther 2005; 47:67.
  76. Duloxetine (cymbalta) for fibromyalgia. Med Lett Drugs Ther 2008; 50:57.
  77. Duloxetine (Cymbalta) for chronic musculoskeletal pain. Med Lett Drugs Ther 2011; 53:33.
  78. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy or chronic pain. Cochrane Database Syst Rev 2009; :CD007115.
  79. Skljarevski V, Zhang S, Desaiah D, et al. Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial. J Pain 2010; 11:1282.
  80. Skljarevski V, Desaiah D, Liu-Seifert H, et al. Efficacy and safety of duloxetine in patients with chronic low back pain. Spine (Phila Pa 1976) 2010; 35:E578.
  81. Skljarevski V, Ossanna M, Liu-Seifert H, et al. A double-blind, randomized trial of duloxetine versus placebo in the management of chronic low back pain. Eur J Neurol 2009; 16:1041.
  82. Smith K, Mattick RP, Bruno R, et al. Factors associated with the development of depression in chronic non-cancer pain patients following the onset of opioid treatment for pain. J Affect Disord 2015; 184:72.
  83. Kroenke K, Bair MJ, Damush TM, et al. Optimized antidepressant therapy and pain self-management in primary care patients with depression and musculoskeletal pain: a randomized controlled trial. JAMA 2009; 301:2099.
  84. Fishbain DA, Cole B, Lewis JE, Gao J. Does pain interfere with antidepressant depression treatment response and remission in patients with depression and pain? An evidence-based structured review. Pain Med 2014; 15:1522.
  85. Derry S, Wiffen PJ, Moore RA, Quinlan J. Topical lidocaine for neuropathic pain in adults. Cochrane Database Syst Rev 2014; :CD010958.
  86. Davies PS, Galer BS. Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs 2004; 64:937.
  87. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev 2007; :CD004846.
  88. Lee SS, Sohn YW, Yoo ES, Kim KH. Neurotoxicity and long lasting analgesia induced by capsaicinoids. J Toxicol Sci 1991; 16 Suppl 1:3.
  89. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004; 328:991.
  90. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev 2010; :CD007402.
  91. Haroutiunian S, Drennan DA, Lipman AG. Topical NSAID therapy for musculoskeletal pain. Pain Med 2010; 11:535.
  92. Towheed TE. Pennsaid therapy for osteoarthritis of the knee: a systematic review and metaanalysis of randomized controlled trials. J Rheumatol 2006; 33:567.
  93. Matthews P, Derry S, Moore RA, McQuay HJ. Topical rubefacients for acute and chronic pain in adults. Cochrane Database Syst Rev 2009; :CD007403.
  94. McCleane G. Topical doxepin hydrochloride reduces neuropathic pain: A randomized, double-blind placebo controlled study. Pain Clin 2000; 12:47.
  95. Xiao L, Mackey S, Hui H, et al. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med 2010; 11:1827.
  96. Yuan RY, Sheu JJ, Yu JM, et al. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology 2009; 72:1473.
  97. Nielsen S, Lintzeris N, Bruno R, et al. Benzodiazepine use among chronic pain patients prescribed opioids: associations with pain, physical and mental health, and health service utilization. Pain Med 2015; 16:356.
  98. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA 2015; 313:2456.
  99. Hill KP. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA 2015; 313:2474.
  100. Andreae MH, Carter GM, Shaparin N, et al. Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. J Pain 2015; 16:1221.
  101. http://www.health.state.mn.us/topics/cannabis/intractable/medicalcannabisreport.pdf.
  102. Nugent SM, Morasco BJ, O'Neil ME, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med 2017; 167:319.
  103. Meng H, Johnston B, Englesakis M, et al. Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis. Anesth Analg 2017; 125:1638.
  104. Ware MA, Wang T, Shapiro S, et al. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain 2015; 16:1233.
  105. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003; 349:1943.
  106. Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. J Pain Symptom Manage 1996; 11:203.
  107. Scascighini L, Toma V, Dober-Spielmann S, Sprott H. Multidisciplinary treatment for chronic pain: a systematic review of interventions and outcomes. Rheumatology (Oxford) 2008; 47:670.
  108. Allegrante JP. The role of adjunctive therapy in the management of chronic nonmalignant pain. Am J Med 1996; 101:33S.
  109. Beck AT. How an anomalous finding led to a new system of psychotherapy. Nat Med 2006; 12:1139.
  110. Okifuji A, Ackerlind S. Behavioral medicine approaches to pain. Med Clin North Am 2007; 91:45.
  111. McBeth J, Prescott G, Scotland G, et al. Cognitive behavior therapy, exercise, or both for treating chronic widespread pain. Arch Intern Med 2012; 172:48.
  112. Nestoriuc Y, Martin A, Rief W, Andrasik F. Biofeedback treatment for headache disorders: a comprehensive efficacy review. Appl Psychophysiol Biofeedback 2008; 33:125.
  113. Stanos SP, McLean J, Rader L. Physical medicine rehabilitation approach to pain. Med Clin North Am 2007; 91:57.
  114. Walsh DM, Basford JR. Transcutaneous electrical nerve stimulation, chapter 47. In: Current Therapy in Pain, Smith HS (Ed), Saunders/Elsevier, Philadelphia, PA 2009. p.541-546.
  115. Nnoaham KE, Kumbang J. Transcutaneous electrical nerve stimulation (TENS) for chronic pain. Cochrane Database Syst Rev 2008; :CD003222.
  116. Cruccu G, Aziz TZ, Garcia-Larrea L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007; 14:952.
  117. Cetas JS, Saedi T, Burchiel KJ. Destructive procedures for the treatment of nonmalignant pain: a structured literature review. J Neurosurg 2008; 109:389.