Topical Agents in the Treatment of Rheumatic Pain

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In rheumatic pain there is good evidence that topical nonsteroidal anti-inflammatory drugs are about as effective as oral nonsteroidal anti-inflammatory drugs, but are probably safer and more tolerable because of much less systemic absorption and lower plasma concentrations. The best information is for topical diclofenac. For topical capsaicin, evidence of efficacy is trivial. For topical rubefacients there is no evidence of efficacy.

Section snippets

Definitions

Classifying topical analgesics is helpful, although a number of authorities lump topical agents together. The British National Formulary, for instance, lists and classifies rubefacients and topical NSAIDs together [4]. The Pharmaceutical Journal more helpfully distinguishes three main categories of topical analgesics [5]:

  • 1.

    Rubefacients: traditional formulations based on salicylate and nicotinate esters, capsaicin and capsicum extracts, and derivatives.

  • 2.

    NSAIDs: diclofenac, felbinac, ibuprofen,

Topical rubefacient (salicylate)

Rubefacients are believed to work by counterirritation, to relieve pain in muscles, joints, and tendons and in nonarticular musculoskeletal conditions, rather than as NSAIDs inhibiting cyclooxygenase responsible for prostaglandin biosynthesis and the development of inflammation.

The information on topical rubefacients (all as salicylate) comes from a 2004 systematic review [6]. No further trials for topical rubefacients were found on more recent searches to March 2008. Twelve randomized,

Topical capsaicin

Capsaicin is the active compound present in chili peppers, responsible for making them hot when eaten. It binds to nociceptors in the skin, causing an initial excitation of the neurones and a period of enhanced sensitivity to noxious stimuli, usually perceived as itching, pricking, or burning sensations. This is followed by a refractory period with reduced sensitivity and, after repeated applications, persistent desensitization; the ability of capsaicin to desensitize nociceptors is exploited

Topical nonsteroidal anti-inflammatory drugs

The usefulness of topical NSAIDs has been questioned, and results of systematic reviews can differ. One systematic review [9] updated a previous review [10] by accepting only higher-quality trials (randomized, double blind); omitting salicylates; and adding newer trials. It concluded that topical NSAIDs were effective in rheumatic pain using a 2-week end point. Another review of topical NSAIDs in musculoskeletal pain [11] published in 2004 concluded that there was no evidence of superior

Is there any science behind topical nonsteroidal anti-inflammatory drugs?

For topical NSAIDs there is information on background biology. That information allows one to investigate the evidence about skin penetration, plasma, and tissue levels of NSAIDs after topical application (Fig. 3).

Discussion

The evidence is quite strong that topical NSAIDs are effective for a considerable proportion of patients with rheumatic pain. As Table 1 demonstrates, information from placebo comparisons in high-quality and validity trials with low risk of bias provided a high degree of comfort for the efficacy of topical NSAIDs, and this has been supported by a considerable additional body of data, especially from longer trials. Topical capsaicin is much less effective, and is supported by only a small amount

What's missing?

There are several gaps in knowledge that need to be filled.

  • 1.

    A greater degree of clarity over classifying topical analgesics. Clinical trials that mix up topical NSAIDs and rubefacients as if they were they same [46], with a similar mechanism of action, do not increase knowledge, and merely confuse matters.

  • 2.

    Publication of what seems to be a large number of well-conducted and longer-duration trials that have been completed, but are not yet in the public domain.

  • 3.

    More safety studies, or publication of

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    • Cited by (0)

    RAM and HJM have received lecture and consultancy fees from pharmaceutical companies with interests in analgesic drugs, including topical analgesics. The authors have received research support from charities and government sources at various times, some of which has related to topical analgesics. No author has any direct stock holding in any pharmaceutical company.

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