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Cochrane systematic review
Topical NSAIDs provide effective relief of acute musculoskeletal pain compared to placebo, with no increase in risk of adverse effects
  1. Rachelle Buchbinder
  1. Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia
  2. Cabrini Hospital and Monash University, Victoria, Australia
  1. Correspondence to Rachelle Buchbinder
    Suite 41 Cabrini Medical Centre, 183 Wattletree Road, Malvern, Victoria 3144, Australia; rachelle.buchbinder{at}

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Acute musculoskeletal pain due to sprains and strains and sporting injuries are a common occurrence. Usual treatment includes rest, ice, compression and elevation; simple analgesia, oral non-steroidal anti-inflammatory drugs (NSAIDs); and various over-the-counter or prescription topical NSAIDs and rubefacients.


In evaluating the evidence for the efficacy and safety of topical NSAIDs for acute musculoskeletal pain, Massey and colleagues identified randomised double-blind trials in adults (16 years or older) that compared topical NSAIDs, applied at least once daily, with placebo or an active treatment.

Trials were included only if there were at least 10 participants per arm, outcomes were measured close to 7 days and if they provided data for the primary outcome of ‘clinical success’ defined as a 50% reduction in patient-reported pain or equivalent categorical measure. Secondary outcomes were number of patients with adverse events (local and systemic) and number of withdrawals (all causes, due to lack of efficacy and adverse events).

Data sources used to identify relevant trials included MEDLINE, EMBASE, Cochrane CENTRAL, the Oxford Pain Relief Database, reference lists of review articles and included studies, manufacturers' websites and Included trials were assessed for risk of bias and methodological quality. Effects were expressed as RRs, numbers needed to treat (NNT) and pooled percentages were used as absolute measures of benefit or harm. Heterogeneity was examined visually, using L'Abbé plots, and meta-analyses were performed using fixed-effects models.


Forty-seven trials involving 5512 participants and 16 different topical NSAIDs applied as creams, gels, foams or patches were included in the review: 31 compared a topical NSAID to placebo, 12 to another active comparator and 4 included both comparator types. Nine trials were excluded because they did not contain usable dichotomous efficacy data. Most studies included participants with acute sporting injuries (strains, sprains and contusions), but an unspecified number included participants with acute (less than 3 months) tendinitis or low back pain. Most trials did not report their method of sequence generation or treatment allocation concealment and details about blinding were unclear in 40%.

For treatment periods of 6–14 days and based upon 31 trials, there was a greater proportion of participants experiencing treatment success in those who received topical NSAIDs (65%, range 31–100%) compared with placebo (43%, range 8–83%), relative benefit 1.5 (1.4–1.6) and NNT benefit 4.5 (95% 3.9 to 5.3). While χ2 (Q) and I2 statistics suggested substantial statistical heterogeneity, indicating that a random-effects model would have been preferred to pool data, the L'Abbé plot indicated that most studies showed benefit of topical NSAID over placebo. Topical diclofenac, ibuprofen, ketoprofen and piroxicam, but not indomethacin or benzydamine, were statistically superior to placebo.

Local irritations described as mild and transient were the only reported adverse effects, but there were no significant differences between groups in the proportion of participants' experiencing a local adverse event or withdrawing due to adverse events.

Based on three trials including 641 participants, topical piroxicam had superior efficacy to topical indomethacin and significantly fewer local adverse events. There were insufficient data to draw any conclusions about the relative efficacy or safety of topical versus oral NSAID, or different modes of topical NSAID delivery.


Massey and colleagues have verified that topical NSAIDs are an effective and safe short-term treatment for acute musculoskeletal pain due to sprains or strains or acute sporting injuries. The greatest benefit occurs in the first week following injury. Insufficient data are available to draw conclusions about the relative efficacy of topical versus oral NSAIDs, although, unlike oral preparations, topical NSAIDs do not appear to cause systemic adverse effects.

Though some trials were excluded because they did not include a dichotomous outcome, it would have been useful to know whether or not their results were broadly consistent with this review. As well, some unpublished trials may exist, though it is unlikely that their inclusion would appreciably alter the conclusions. The review excluded trials of children less than 16 years of age, whereas older people were underrepresented; however, it is likely that the results are broadly generalisable.

It is arguable whether trials of acute tendinitis and low back pain should have been included in this review, as they likely differ in patho-aetiology and course from sprains and strains and may therefore respond differently to treatment. However, the results of this review are consistent with the findings of another Cochrane review that evaluated topical NSAIDs for lateral elbow pain,1 whereas a Cochrane review of NSAIDs for acute low back pain identified too few studies to be able to draw conclusions about topical NSAIDs.2

This review does not tell us whether topical NSAIDs should be preferred over topical rubefacients, such as the salicylates, which are proposed to relieve acute pain by causing local irritation. However, a recent Cochrane review concluded that rubefacients were unlikely to be beneficial for acute musculoskeletal pain and compared poorly to topical NSAIDs for more chronic pain.3 Therefore, topical NSAIDs are the preferred topical therapy to relieve acute musculoskeletal pain due to sprains and strains and acute sporting injuries.


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  • Competing interests None.