What is the best analgesic for Musculoskeletal (MSK) pain?

Best Analgesic for Musculoskeletal Pain

Acetaminophen should be the first-line analgesic for musculoskeletal pain, with NSAIDs reserved for patients who fail acetaminophen or have clear inflammatory components. 1

First-Line Therapy: Acetaminophen

• Start with acetaminophen up to 4,000 mg daily as initial therapy for MSK pain due to its proven effectiveness and superior safety profile compared to NSAIDs 1, 2
• Acetaminophen provides comparable pain relief to NSAIDs in acute musculoskeletal trauma, with no clinically significant difference in pain reduction at rest or with movement 3
• The American Geriatrics Society strongly recommends acetaminophen as initial and ongoing pharmacotherapy for persistent musculoskeletal pain 1
• Do not exceed 4,000 mg per 24 hours, including "hidden sources" from combination products 1

Contraindications to Acetaminophen

• Absolute: Liver failure 1
• Relative: Hepatic insufficiency, chronic alcohol abuse or dependence 1

Second-Line Therapy: NSAIDs

NSAIDs should only be considered when acetaminophen fails and after careful risk stratification. 1

• NSAIDs provide superior pain control and functional outcomes compared to acetaminophen in patients with inflammatory arthritis, but this advantage is less clear in non-inflammatory MSK pain 1
• For knee osteoarthritis specifically, NSAIDs are recommended only in patients unresponsive to acetaminophen, particularly those with effusion 1
• NSAIDs carry 3- to 5-fold increased risk of serious GI complications including bleeding, perforation, and obstruction 1
• NSAID use has surpassed H. pylori as the most common risk factor for bleeding ulcers, found in 53% of cases 1

NSAID Risk Stratification

Absolute contraindications to NSAIDs: 1

• Active peptic ulcer disease
• Chronic kidney disease
• Heart failure

Relative contraindications: 1

• Hypertension
• History of peptic ulcer disease or H. pylori
• Concomitant corticosteroids or SSRIs

GI Protection When NSAIDs Are Necessary

• All patients taking nonselective NSAIDs must use a proton pump inhibitor or misoprostol for gastroprotection 1
• COX-2 selective inhibitors have lower GI risk than traditional NSAIDs but still require gastroprotection if combined with aspirin 1
• Never prescribe more than one NSAID or COX-2 inhibitor simultaneously 1

COX-2 Inhibitors vs Traditional NSAIDs

• COX-2 inhibitors (coxibs) show equal efficacy to traditional NSAIDs for spinal and peripheral joint pain 1
• Coxibs have lower risk of serious GI events than nonselective NSAIDs 1
• Emerging evidence suggests cardiovascular toxicity with both coxibs and traditional NSAIDs, so choice should be based on individual GI and cardiovascular risk profiles 1

Combination Therapy: Not Superior

The combination of ibuprofen and acetaminophen provides no additional benefit over either agent alone for acute musculoskeletal injuries 4

• A randomized trial of 90 ED patients found no significant difference in pain reduction between ibuprofen 800 mg, acetaminophen 1,000 mg, or their combination at 20,40, and 60 minutes 4
• Need for rescue analgesics was similar across all groups 4

Topical NSAIDs: Consider for Localized Pain

• Topical NSAIDs (diclofenac, ketoprofen) have strong evidence for musculoskeletal pain with minimal systemic absorption and high safety 1
• Particularly appropriate for older adults or those at high risk for systemic NSAID complications 1
• Topical formulations provide effective pain relief with fewer side effects than oral NSAIDs 5

Agents to Avoid

Muscle relaxants are not effective for musculoskeletal pain and should not be prescribed: 6

• Their effects are nonspecific and not related to actual muscle relaxation 6
• Associated with increased fall risk, particularly in older adults 6
• Most trials involve acute rather than chronic pain, with limited evidence of benefit 1

Systemic corticosteroids have no role in routine MSK pain management 1

Opioids are not first-line therapy for chronic musculoskeletal pain due to questionable effectiveness, high rates of adverse events (50% of patients), and significant withdrawal rates (25%) 1

Clinical Algorithm

1. Start with acetaminophen up to 4,000 mg daily after confirming no hepatic contraindications 1
2. If inadequate response after appropriate trial, assess for inflammatory component (effusion, warmth, significant morning stiffness) 1
3. If inflammatory features present or acetaminophen fails, perform cardiovascular and GI risk assessment before considering NSAIDs 1
4. If NSAIDs indicated, prescribe lowest effective dose with mandatory PPI gastroprotection 1
5. For localized pain, consider topical NSAIDs as safer alternative to systemic therapy 1