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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.

Chronic pain is a highly prevalent condition that is experienced by 1 in 5 US adults.1 In addition to being the leading cause of disability, chronic pain is associated with reduced life expectancy.2,3 Unlike acute pain, which signals tissue injury that is transient, chronic pain is a complex phenomenon that persists for 3 months or longer, after injured tissue has healed, and is influenced by biologic, psychological, and social factors.4,5

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments
For knee or hand osteoarthritis, consider topical nonsteroidal anti-inflammatory drugs as a first-line treatment because of effectiveness and minimal adverse effects, followed by oral nonsteroidal anti-inflammatory drugs (due to similar effectiveness with more adverse effects) and duloxetine; recommendations for hip osteoarthritis are similar, with a lack of evidence for topical drugs.13–15 ASystematic reviews showing significant reduction in pain scores
For chronic low back pain, preferentially use topical nonsteroidal anti-inflammatory drugs and oral nonsteroidal anti-inflammatory drugs and serotonin norepinephrine reuptake inhibitors.4,22,27 BSystematic reviews showing small to moderate pain benefit over short periods
For chronic low back pain, avoid using antiepileptics, including gabapentinoids, due to no benefit and associated harms.4,28 BExpert opinion and consensus guidelines from mostly small studies
For neuropathic pain, use gabapentin, pregabalin, or duloxetine based on evidence for treatment of postherpetic neuralgia and diabetic neuropathy.29,35–37 ASystematic reviews showing moderate pain benefit
For fibromyalgia pain, consider pregabalin if tolerated at a dose that provides therapeutic benefit or consider duloxetine and milnaciprine.43–45 BSystematic reviews demonstrating moderate pain benefit in variable quality studies
Prescribe serotonin-norepinephrine reuptake inhibitors, such as duloxetine and milnacipran, for the treatment of fibromyalgia, neuropathic pain, and musculoskeletal pain and topical nonsteroidal anti-inflammatory drugs for chronic musculoskeletal pain.22,49 ASystematic reviews showing small pain benefit

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

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.

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