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#159 NSAIDs: Inflamed effects on inflammation?

Do non-steroidal anti-inflammatory drugs (NSAIDs) reduce swelling and inflammation in acute injury?

Randomized Controlled Trials (RCTs) of NSAIDs effect on musculoskeletal injury swelling show highly inconsistent results:  Some slight improvements (2-11%), some slight worsening (8%) and most no effect. It is unlikely NSAIDs have any reliable effect on acute injury swelling but they do improve pain for ~1 in 4 over one week.   

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NSAIDs versus other drugs: 
  • Systematic review, ten soft tissue injury RCTs:1 
    • Mostly found no difference between adequately dosed NSAIDs (like diclofenac 150 mg/day or ibuprofen 1600 mg/day) versus acetaminophen, dihydrocodeine, or acetaminophen-opioid combinations. 
    • One RCT (68 patients, mixed injuries): Naproxen 1100 mg/day statistically reduced swellin~6% versus dextropropoxyphene (Darvon) at three days. 
    • One RCT (86 patients, ankle sprain): Diclofenac 150 mg/day statistically worse swelling ~8% versus acetaminophen at three days.2 
    • Limitations: Groups treated differently,3 inconsistent blinding,1 suboptimal doses sometimes,1 and swelling secondary outcome.1  
NSAID versus placebo: 
  • No systematic review. Eight individual RCTs, statistically significant results in swelling versus placebo. 
    • 66 knee injury patients:4 Diclofenac reduced (undefined) swelling. 
      • No swelling: 71% diclofenac versus 35% placebo. 
    • 364 ankle sprain patients:5 Piroxicam 40 mg made no difference in swelling by volumetric assessment 
      • Piroxicam increased clinically assessed swelling (no swelling: 20% piroxicam versus 48% placebo).  
    • 60 ankle injury patients:6 Nimulside 200 mg/day reduced swelling by volumetric assessment ~11% more than placebo.6 
    • 44 hamstring injury patients:7 Diclofenac 150 mg/day no difference. 
    • 92 ankle injury patients:8 No difference with diclofenac 150 mg/day or piroxicam 20 mg/day. 
    • 68 ankle injury patients:9 Ibuprofen 2400 mg/day no difference. 
    • Two ankle sprain RCTs (60 and 108 patients):10,11 Diclofenac 150 mg/day and piroxicam 20 mg/day reduced swelling by ~25 mL (1.65%) more than placebo at three days.10,11 
  • Swelling should be assessed by volume (example water displacement) but frequently was not.    
  • According to systematic reviews of topical NSAIDs and older RCTs, NSAIDs are effective for pain relief in acute injury.4-6,8,12 
    • Topical NSAID example, 50% reduction in pain for acute musculoskeletal injury: Number Needed to Treat (NNT)=at 6-8 days and =10 at 9-14 days. 

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  • Adrienne J Lindblad BSP ACPR PharmD
  • Constance M Lebrun MDCM MPE CCFP(SEM) Dip. Sports Med

1. Jones P, Dalziel SR, Lamdin R, et al. Cochrane Database Syst Rev. 2015; 7:CD007789.

2. Lyrtzis C, Natsis K, Papadopoulos C, et al. Foot Ankle Int. 2011; 32(6):571-5.

3. Beveridge K. Pharmacotherapeutica. 1985; 4(6):393-8.

4. Van Heerden JJ. S Afr Med J. 1977; 52:396-9.

5. Slatyer MA, Hensley MJ, Lopert R. Am J Sports Med. 1997; 25:544-53.

6. Dreiser RL, Riebenfeld D. Drugs. 1993; 46 (suppl 1):183-6.

7. Reynolds JF, Noakes TD, Schwellnus MP, et al. S Afr Med J. 1995; 85:517-22.

8. Bahamonde LA, Saavedra HC. J Int Med Res. 1990 Mar-Apr; 18(2):104-11.

9. Fredberg U, Hansen PA, Skinhøj A. Am J Sports Med. 1989; 17(4):564-6.

10. Morán M. J Int Med Res. 1991; 19:121-30.

11. Morán M. Curr Med Res Opin. 1990; 12(4):268-74.

12. Allan GM, Turner R. Tools for Practice. Available at: Accessed January 24, 2015.

Authors do not have any conflicts to disclose.