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Am Fam Physician. 2021;104(1):63-72

Related editorial: Management of Acute Pain from Musculoskeletal Injuries: Guidance for Family Physicians

Related practice guideline: Management of Acute Pain from Non–Low Back Musculoskeletal Injuries: Guidelines from AAFP and ACP

Related letter: Should Muscle Relaxants Be Used as Adjuvants in Patients With Acute Low Back Pain?

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Pharmacologic management of acute pain should be tailored for each patient, including a review of treatment expectations and a plan for the time course of prescriptions. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line treatment options for most patients with acute mild to moderate pain. Topical NSAIDs are recommended for non–low back, musculoskeletal injuries. Acetaminophen is well tolerated; however, lower doses should be used in patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder. Nonselective NSAIDs are effective but should be used with caution in patients with a history of gastrointestinal bleeding, cardiovascular disease, or chronic renal disease. Selective cyclooxygenase-2 NSAIDs are a more expensive treatment alternative and are used to avoid the gastrointestinal adverse effects of nonselective NSAIDs. Adjunctive medications may be added as appropriate for specific conditions if the recommended dose and schedule of first-line agents are inadequate (e.g., muscle relaxants may be useful for acute low back pain). For severe or refractory acute pain, treatment can be briefly escalated with the use of medications that work on opioid and monoamine receptors (e.g., tramadol, tapentadol) or with the use of acetaminophen/opioid or NSAID/opioid combinations. The opioid epidemic has increased physician and community awareness of the harms of opioid medications; however, severe acute pain may necessitate short-term use of opioids with attention to minimizing risk, including in patients on medication-assisted therapy for opioid use disorder.

Acute pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Acute pain lasts from a few days up to 12 weeks and is typically prompted by a specific event and caused by direct tissue damage that is likely to resolve. A person's perception of pain is controlled by biophysical factors, including sensory, emotional, cognitive, and social components.1 Pharmacologic management of acute pain should be tailored for each patient, and effective management may prevent the transition to chronic pain.2

Clinical recommendation Evidence rating Comments
Topical nonsteroidal anti-inflammatory drugs are safe and effective for treating acute pain.18,19,20 A Systematic review, consistent randomized controlled trials, evidence-based guidelines
Nonsteroidal anti-inflammatory drugs, acetaminophen, or a combination is an effective initial treatment approach for acute pain syndromes. Medication selection should be based on minimizing risks for the specific patient.13,17,23,25 A Systematic reviews, consistent randomized controlled trials, clinical guidelines
Muscle relaxants are effective adjunctive medications for acute low back pain and neck pain.43,44 B Systematic review, multiple randomized controlled trials
Gabapentinoids and antidepressant medications used to treat chronic neuropathic pain should not be used to treat acute pain.5356 B Meta-analysis (gabapentinoids), systematic review (gabapentinoids and antidepressants), mixed results from high-quality studies (gabapentinoids)
Cannabinoids used to treat chronic neuropathic pain should not be used to treat acute pain.60 C Mixed results from low-quality studies
Opioids should be used for no more than three days, only for severe or refractory acute pain, and only in combination with other medications.12,17,25,63,64 C Expert consensus opinion, clinical guidelines

This article provides a tiered pharmacologic approach for safe and effective management of acute pain in ambulatory and inpatient settings (Table 13). Most data are derived from studies of acute musculoskeletal pain and postoperative pain. Nonpharmacologic management of acute pain, such as nerve blocks,4,5 acupuncture,6 transcutaneous electrical nerve stimulation,7 mindfulness,8 and massage,9 is reviewed elsewhere.

Medication/dosingPain levelBest useRiskCommentsCost*
Orally or rectally: 325 to 1,000 mg every 4 to 6 hours
IV: ≥ 50 kg, 650 mg every 4 hours or 1,000 mg every 6 hours; < 50 kg, 12.5 mg per kg every 4 hours or 15 mg per kg every 6 hours
Maximum: 75 mg per kg per day, not to exceed 4,000 mg per day
Mild to moderateMild osteoarthritis
Generalized headache
Ankle sprain
HepatotoxicityWell tolerated
First-line treatment in patients with renal and hepatic impairment and cardiovascular disease
≤ 2,000 mg per day in patients with advanced hepatic disease and severe alcohol use disorder
May be combined with NSAIDs for postoperative pain
Tablet: $3 ($5)
Suppository: — ($12)
Nonselective NSAIDs
Ibuprofen: 200 to 400 mg every 6 to 8 hours
Maximum: 1,200 mg per day
Mild to moderateMigraine
Low back pain
Renal colic
Postoperative pain
Bronchospasm (aspirin)
Anti-inflammatory effects
Consider adding proton pump inhibitor or switching to a selective COX-2 NSAID to decrease gastrointestinal risk
May have a ceiling analgesic effect
$5 ($10)
Naproxen: 250 mg every 6 to 8 hours or 500 mg every 12 hours
Maximum: 1,000 mg per day
$10 ($200)
Diclofenac: 50 mg every 8 hours
Maximum: 150 mg per day
$10 ($750)
Orally: 10 mg every 4 to 6 hours
IM: 30 to 60 mg as a single dose or 15 to 30 mg every 6 hours
IV: 10 to 15 mg every 6 hours
Maximum: oral 40 mg per day; IM/IV 120 mg per day
Tablets: $20 (—)
Syringes: $15 (NA)
Meloxicam: 7.5 to 15 mg per day
Maximum: 15 mg per day
$10 ($500)
Selective COX-2 NSAIDs
Meloxicam: 7.5 mg per dayMild to moderateMigraine
Low back pain
Renal colic
Postoperative pain
More expensive than nonselective NSAIDs
Celecoxib has a U.S. Food and Drug Administration boxed warning for increased risk of cardiovascular disease
$10 ($300)
Celecoxib (Celebrex): 100 to 200 mg per day$20 ($225)
Acetaminophen plus NSAID combinations
See individual medicationsMild to moderate
May continue use for severe pain
Pain refractory to either agent alone
Postoperative pain
See individual medicationsCombinations have superior effectiveness vs. single agents
Effective for postoperative pain
Combining medications has lower risk of adverse effects than high doses of single agents
See individual medications
Opioid plus acetaminophen or NSAID combinations
Hydrocodone/acetaminophen: 2.5 mg/325 mg to 10 mg/325 mg every 4 to 6 hours
Maximum: 4,000 mg per day of acetaminophen
Persistent moderate to severe painPain refractory to other agents
Postoperative pain
Fracture pain
See individual medicationsSuperior effectiveness compared with single agent
Opioid sparing effect with decreased risk of adverse events
$25 ($150)
Hydrocodone/ibuprofen: 2.5 mg/200 mg to 10 mg/ 200 mg every 6 to 8 hours
Maximum: 1,200 mg per day of ibuprofen
$40 ($50)
Oxycodone/acetaminophen 2.5 mg/325 mg to 10 mg/ 325 mg every 4 to 6 hours
Maximum: 4,000 mg per day of acetaminophen
$25 ($800)
Dual-action opioid medications
Tramadol (Ultram): 25 mg every 4 to 6 hours, titrated to 50 to 100 mg as needed
Maximum: 400 mg per day
Persistent moderate to severe painPain refractory to other agents, with goal of limiting more potent opioidsDizziness, sedation, constipation
Opioid use disorder
Serotonin syndrome
Tramadol decreases the seizure threshold
Adverse effects comparable to full agonists with less pain relief$10 ($110)
Tapentadol (Nucynta): 50 to 100 mg every 4 to 6 hours
Maximum: 600 mg per day
— ($215)
Full agonist opioids
Oxycodone: 5 mg orally every 4 to 6 hours as neededPersistent severe painShort course for severe acute pain
Pain refractory to other medications
Nausea, emesis
Respiratory depression
Opioid use disorder
Limit prescription to 3-day course
Continue other medication classes as tolerated
Higher doses may be required for patients taking chronic opioid therapy or naltrexone (Revia)
$10 ($60)
Morphine: 1 to 4 mg IV every 4 hours titrated up as needed; 10 to 15 mg IV every 4 to 6 hours for severe pain
Maximum: limited by opioid-related adverse effects
Hydromorphone (Dilaudid)
Orally: 2 to 4 mg every 4 to 6 hours
IV: 0.2 to 1 mg every 2 to 3 hours
Maximum: reserve for severe pain; use caution with dosing to prevent oversedation
Tablets: $10 ($125) IV: NA

Racial and ethnic inequities exist in the management of acute pain. Patients from minority groups are more likely to have their pain underestimated and undertreated compared with White patients.10 African American and Hispanic patients are less likely to receive opioid analgesics despite pain severity.10 African Americans experience both a higher number and magnitude of disparities in pain management than any other group.11 Family physicians should apply the goals and principles of acute pain management to all patients to avoid continued harm to these marginalized groups.

A more detailed discussion of pain management in specific populations, including children and pregnant patients, is beyond the scope of this article. Evidence for specific pain syndromes is highlighted in this article when available.

Goals and Principles

The goal of treating acute pain is to decrease suffering, improve function, and minimize adverse effects. Management should include a review of treatment expectations and a plan for the time course of prescriptions. Treatment of acute pain should include addressing the cause of the pain when appropriate, such as immobilizing a fracture or draining an abscess. The World Health Organization's pain relief ladder provides a framework that was developed to address the need for effective management of cancer-related pain and encourage prompt initiation and appropriate escalation of scheduled opioids for pain that is not relieved with nonopioid medications.12 The use of the pain relief ladder in guiding treatment of acute pain has been called into question.13

Because of the increased recognition of the harm caused by the use of opioids, newer guidelines recommend that opioids be reserved for severe or refractory pain.14,15 Regular reassessments of opioid therapy allow for the addition or discontinuation of pharmacologic and nonpharmacologic treatments as indicated, with a goal of tapering off all medications as quickly as possible.

Combinations of medications may provide maximal benefit and decrease dosage requirements of individual agents. An overview of Cochrane reviews showed that ibuprofen, 200 mg, alone has a number needed to treat (NNT) of 3 to achieve a 50% reduction in pain, whereas the same dose of ibuprofen combined with acetaminophen, 500 mg, has an NNT of 1.6. The NNT of acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, is only marginally better at 1.5.16 The rates of adverse events are sometimes lower when using combination treatments and are low for short-term analgesics. An additional overview of Cochrane reviews reported that the relative risk of any adverse event from a single dose of ibuprofen, 200 mg, is 0.9 (95% CI, 0.7 to 1.02). For the combination of ibuprofen, 200 mg, and acetaminophen, 500 mg, the relative risk is 0.7 (95% CI, 0.6 to 0.9).17

Topical Analgesics

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) locally inhibit cyclooxygenase (COX) receptors when absorbed through the skin.18 Topical NSAIDs can be rubbed directly on unbroken skin or applied via a transdermal patch and are effective for acute musculoskeletal strains and sprains.18,19 Topical NSAIDs provide up to 50% pain relief compared with placebo. Diclofenac gel has shown superiority among topical NSAIDs (NNT = 2). The rates of systemic or local adverse events with topical NSAIDs are similar to topical placebo (4.3% and 4.6%, respectively) in the treatment of acute pain.18 Systemic absorption is 1% to 7% across all topical NSAIDs at recommended dosages.18 There is no evidence regarding the rates of adverse cardiovascular events and renal disease when used in the short term. Topical NSAIDs have a low risk of gastrointestinal (GI) bleeding, even with long-term use; however, patients at high risk should be cautious. Guidelines from the American College of Physicians and the American Academy of Family Physicians recommend topical NSAIDs as first-line therapy for acute non–low back, musculoskeletal pain.14

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