Previous article
Provision of Quality Contraceptive Services: Updates From National Guidelines
Aug 2025
Next article
Practice Alert: Meningococcal Vaccines

Nonopioid Pharmacologic Management of Chronic Noncancer Pain

Randi Sokol, MD, MPH, MMedEd
Ellie Grossman, MD, MPH
Rebecca Bourgery, PharmD

American Family Physician. 2025;112(2):187-196.

Author disclosure: No relevant financial relationships.

This clinical content conforms to AAFP criteria for CME.

Published online July 15, 2025.

Chronic pain (ie, present for at least 3 months) is highly prevalent, affecting 1 in 5 US adults, and can be debilitating. Treatment includes a comprehensive, patient-centered biopsychosocial approach that identifies pain type, focuses on improving function and quality of life, sets reasonable expectations around pain control, promotes self-management strategies, addresses mental health comorbidities, and includes pharmacotherapy and nonpharmacotherapy options. For osteoarthritis, topical and oral nonsteroidal anti-inflammatory drugs (NSAIDs) provide significant pain relief; limited evidence suggests benefit from serotonin-norepinephrine reuptake inhibitors (SNRIs) and gabapentinoids. For chronic low back pain, no pharmacotherapy offers significant pain or functional benefit; evidence is limited to short-term outcomes. Oral and topical NSAIDs and SNRIs appear to improve pain slightly in the short term. For neuropathic pain, duloxetine, gabapentin, pregabalin, and high-concentration (8%) topical capsaicin provide moderate pain benefit. For fibromyalgia, pregabalin has the best evidence for moderate pain benefit, followed by the SNRIs duloxetine and milnacipran. Opioids should be considered only after other strategies have been tried and after risk-benefit assessment.

RANDI SOKOL, MD, MPH, MMedEd, is an associate professor in the Department of Family Medicine, Cambridge Health Alliance, Malden, Massachusetts.

ELLIE GROSSMAN, MD, MPH, is the medical director for primary care and behavioral health integration at Cambridge Health Alliance, Cambridge, Massachusetts; and instructor in the Department of Internal Medicine, Harvard Medical School, Boston.

REBECCA BOURGERY, PharmD, is a senior clinical pharmacist specialist in the Cambridge Health Alliance, Cambridge, Massachusetts.

Published online July 15, 2025

Address correspondence to Randi Sokol, MD, MPH, MMedEd, at rsokol@challiance.org.

Author disclosure: No relevant financial relationships.

  1. 1.Rikard SM, Strahan AE, Schmit KM, et al. Chronic pain among adults—United States, 2019–2021. MMWR Morb Mortal Wkly Rep. 2023;72(15):379-385.
  2. 2.Murray CJ, Atkinson C, Bhalla K, et al. The state of US health, 1990–2010. JAMA. 2013;310(6):591-608.
  3. 3.Smith D, Wilkie R, Uthman O, et al. Chronic pain and mortality: a systematic review. PLoS One. 2014;9(6):e99048.
  4. 4.McDonagh M, Selph S, Buckley D, et al. Nonopioid Pharmacologic Treatments for Chronic Pain. Comparative Effectiveness Review No. 228. April 2020. Accessed February 12, 2025. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/nonopioid-chronic-pain.pdf
  5. 5.Banerjee S, Argáez C. Multidisciplinary Treatment Programs for Patients With Acute or Subacute Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Canadian Agency for Drugs and Technologies in Health; 2019.
  6. 6.American Academy of Family Physicians. AAFP Chronic Pain Management Toolkit. Accessed February 12, 2025. https://www.aafp.org/family-physician/patient-care/care-resources/pain-management/aafp-chronic-pain-management-toolkit.html
  7. 7.Meints SM, Edwards RR. Evaluating psychosocial contributions to chronic pain outcomes. Prog Neuropsychopharmacol Biol Psychiatry. 2018;87(pt B):168-182.
  8. 8.Gatchel RJ, Peng YB, Peters ML, et al. The biopsychosocial approach to chronic pain. Psychol Bull. 2007;133(4):581-624.
  9. 9.Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth. 1997;78(5):606-617.
  10. 10.Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol. 2020;72(2):220-233.
  11. 11.Roth SH, Shainhouse JZ. Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee. Arch Intern Med. 2004;164(18):2017-2023.
  12. 12.Peniston JH, Gold MS, Wieman MS, et al. Long-term tolerability of topical diclofenac sodium 1% gel for osteoarthritis in seniors and patients with comorbidities. Clin Interv Aging. 2012;7:517-523.
  13. 13.Derry S, Conaghan P, Da Silva JAP, et al. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2016(4):CD007400.
  14. 14.da Costa BR, Pereira TV, Saadat P, et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis. BMJ. 2021;375(2321).
  15. 15.Leaney AA, Lyttle JR, Segan J, et al. Antidepressants for hip and knee osteoarthritis. Cochrane Database Syst Rev. 2022(10):CD012157.
  16. 16.Du Z, Chen H, Cai Y, et al. Pharmacological use of gamma-aminobutyric acid derivatives in osteoarthritis pain management: a systematic review. BMC Rheumatol. 2022;6(1):28.
  17. 17.Leopoldino AO, Machado GC, Ferreira PH, et al. Paracetamol versus placebo for knee and hip osteoarthritis. Cochrane Database Syst Rev. 2019(2):CD013273.
  18. 18.Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005(2):CD002946.
  19. 19.Singh JA, Noorbaloochi S, MacDonald R, et al. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2015(1):CD005614.
  20. 20.Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults—an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017(5):CD008609.
  21. 21.Cashin AG, Wand BM, O’Connell NE, et al. Pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2023(4):CD013815.
  22. 22.Shi C, Ye Z, Shao Z, et al. Multidisciplinary guidelines for the rational use of topical non-steroidal anti-inflammatory drugs for musculoskeletal pain (2022). J Clin Med. 2023;12(4):1544.
  23. 23.Arbus L, Fajadet B, Aubert D, et al. Activity of tetrazepam (Myolastan) in low back pain. Clin Trials J. 1990;27(4):258-267.
  24. 24.Salzmann E, Pforringer W, Paal G, et al. Treatment of chronic low-back syndrome with tetrazepam in a placebo controlled double-blind trial. J Drug Dev. 1992;4(4):219-228.
  25. 25.van Tulder MW, Touray T, Furlan AD, et al. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003(2):CD004252.
  26. 26.Oldfield BJ, Gleeson B, Morford KL, et al. Long-term use of muscle relaxant medications for chronic pain: a systematic review. JAMA Netw Open. 2024;7(9):e2434835.
  27. 27.Ferraro MC, Urquhart DM, Ferreira GE, et al. Antidepressants for low back pain and spine-related leg pain. Cochrane Database Syst Rev. 2025(3):CD001703.
  28. 28.National Institute for Health and Care Excellence (NICE). Low back pain and sciatica in over 16s: assessment and management. NICE guideline NG59. Updated December 11, 2020. Accessed May 2, 2025. https://www.nice.org.uk/guidance/NG59
  29. 29.Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014(1):CD007115.
  30. 30.Gallagher HC, Gallagher RM, Butler M, et al. Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015(8):CD011091.
  31. 31.Aiyer R, Barkin RL, Bhatia A. Treatment of neuropathic pain with venlafaxine: a systematic review. Pain Med. 2017;18(10):1999-2012.
  32. 32.Derry S, Phillips T, Moore RA, et al. Milnacipran for neuropathic pain in adults. Cochrane Database Syst Rev. 2015(7):CD011789.
  33. 33.Moore RA, Derry S, Aldington D, et al. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015(7):CD008242.
  34. 34.Derry S, Wiffen PJ, Aldington D, et al. Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015(1):CD011209.
  35. 35.Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017(6):CD007938.
  36. 36.Derry S, Bell RF, Straube S, et al. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev. 2019(1):CD007076.
  37. 37.Wiffen PJ, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia—an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013(11):CD010567.
  38. 38.Wiffen PJ, Derry S, Moore RA, et al. Levetiracetam for neuropathic pain in adults. Cochrane Database Syst Rev. 2014(7):CD010943.
  39. 39.Derry S, Rice ASC, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017(1):CD007393.
  40. 40.Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2012(9):CD010111.
  41. 41.Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328(7446):991.
  42. 42.Chaparro LE, Wiffen PJ, Moore RA, et al. Combination pharmacotherapy for the treatment of neuropathic pain in adults. Cochrane Database Syst Rev. 2012(7):CD008943.
  43. 43.Derry S, Cording M, Wiffen PJ, et al. Pregabalin for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 2016(9):CD011790.
  44. 44.Welsch P, Üçeyler N, Klose P, et al. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia. Cochrane Database Syst Rev. 2018(2):CD010292.
  45. 45.Moore A, Bidonde J, Fisher E, et al. Effectiveness of pharmacological therapies for fibromyalgia syndrome in adults: an overview of Cochrane Reviews. Rheumatology (Oxford). 2025;64(5):2385-2394.
  46. 46.Cooper TE, Derry S, Wiffen PJ, et al. Gabapentin for fibromyalgia pain in adults. Cochrane Database Syst Rev. 2017(1):CD012188.
  47. 47.Walitt B, Urrútia G, Nishishinya MB, et al. Selective serotonin reuptake inhibitors for fibromyalgia syndrome. Cochrane Database Syst Rev. 2015(6):CD011735.
  48. 48.Carville SF, Arendt-Nielsen L, Bliddal H, et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008;67(4):536-541.
  49. 49.Birkinshaw H, Friedrich CM, Cole P, et al. Antidepressants for pain management in adults with chronic pain: a network meta-analysis. Cochrane Database Syst Rev. 2023(5):CD014682.
  50. 50.Voute M, Morel V, Pickering G. Topical lidocaine for chronic pain treatment. Drug Des Devel Ther. 2021;15:4091-4103.
  51. 51.Dowell D, Ragan KR, Jones CM, et al. CDC clinical practice guideline for prescribing opioids for pain. MMWR Recomm Rep. 2022;71(3):1-95.
  52. 52.Webster L, Gudin J, Raffa RB, et al. Understanding buprenorphine for use in chronic pain: expert opinion. Pain Med. 2020;21(4):714-723.
  53. 53.Sonoda K, Wakabayashi M. Long-term opioid therapy for nonterminal pain. Am Fam Physician. 2025;111(6):508-514.
Previous article
Provision of Quality Contraceptive Services: Updates From National Guidelines
Aug 2025
Next article
Practice Alert: Meningococcal Vaccines

Current issue

May 2026

May 2026

Copyright © 2026 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. See permissions for copyright questions and/or permission requests.