Background for Fast Fact #249     Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed drugs in the treatment of musculoskeletal pain.  In the United States, diclofenac is the only FDA approved topical NSAID and it is available in a few different formulations – an over-the-counter gel (Voltaren), a topical solution (PENNSAID) available by prescription, and a topical patch (Flector) also available by prescription (1).  This Fast Fact reviews the pharmacology, clinical efficacy and adverse effects of topical NSAIDs for the treatment of musculoskeletal pain.

Pharmacology     High plasma concentrations of oral NSAIDs are required to achieve effective tissue concentrations at the site of pain and inflammation. Topical NSAIDs are believed to deliver superficial tissue concentrations with minimal systemic absorption. Plasma concentrations following topical administration of the diclofenac sodium gel, and the diclofenac patch are far lower than levels found following oral administration of diclofenac (0.6%-2.2%, and less than 1%, of oral systemic levels, respectively). Time to peak serum concentration for topical formulations is approximately 10-20 hours (2).

Clinical evidence     NSAIDs are often recommended as first-line treatment for mild-to-moderate musculoskeletal pain mainly because of their good safety profile (3,4).  A Cochrane review of the efficacy of topical NSAIDS in the treatment of acute musculoskeletal pain (sprains, strains, contusions) found that compared to placebo, the number needed to treat (NNT) was between 3.2 to 9 to achieve 50% pain relief over depending upon the formulation and pain syndrome (5). In chronic conditions such as chronic low back pain, there is less evidence to support the efficacy of topical NSAIDs (5,6). There are virtually no data about topical NSAID use in patient populations commonly seen in palliative care settings such as terminal illness or cancer (7,8). A literature review identified a single study which showed no benefit from a topical NSAID cream over placebo in the relief of pain related to pressure ulcers (8).

Adverse effects    Patients taking oral NSAIDs for ≥5 days at least twice annually have a 4.21 relative risk of gastrointestinal events compared to those who do not (7). Conversely, topical NSAIDs have a high margin of safety and have not been associated with acute renal failure or upper GI adverse events. Mild local adverse effects occur at approximately the same rate (6%) in patients treated with topical NSAIDs or topical placebo (5,6).

Cost   Over the counter formulations like the diclofenac gel are affordable and may cost about $65 for a 10-day supply. For comparison, oral ibuprofen may cost about $5 or less for a 10 day supply.  Prescription patches and topical solutions are even more costly and tend to cost more than $100 for a 10-day supply.

Summary     For acute musculoskeletal pain (excluding low back pain), topical NSAIDS are more effective than placebo and are associated with fewer adverse events than oral NSAIDs. In other words, current data suggest topical NSAIDs are appropriate for patients with a flare of single joint arthritis or acute musculoskeletal injury. Given the expense of topical NSAIDS and unclear clinical benefit over prolonged time periods, they are not recommended for chronic musculoskeletal pain.  Their use for cancer-related pain syndromes and other indications is entirely empiric.

References 

1. McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med. 2013; 14(Supp 1):S35-9.
2. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.
3. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain: a Joint Clinical Practice Guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007; 7:478-91.
4. Honvo G, Leclercq V, Geerinck A, et al.  Safety of topical non-steroidal anti-inflammatory drugs in osteoarthritis: outcomes of a systematic review and meta-analysis.  Drugs and Aging 2019; 36;45-64.
5. Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults‐an overview of Cochrane Reviews. Cochrane Database of Systematic Reviews. 2017(5).
6. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain: An updated Cochrane review. Spine.  2008; 33:1766-74.
7. Gotzsche P. NSAIDs. Clinical Evidence. 2009; 6(1108).
8. Magee DJ, Jhanji S, Poulogiannis G, et al. Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence. British journal of anaesthesia. 2019 Aug 1;123(2):e412-23.
9. Prentice WM, Roth LJ, Kelly P. Topical benzydamine cream and the relief of pressure pain. Palliat Med. 2004; 18:520-4.
10. Singh G, Triadafilopoulus G. Epidemiology of NSAID-induced GI complications. J Rheumatol. 1999; 26:18-24.

Authors’ Affiliation:   University of Pittsburgh Medical Center, Pittsburgh, PA.
Version History: Originally published January 2012; Copy-re-edited August 2015; reviewed and updated again in June 2025.
Conflicts of Interest: None to report.