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Topical analgesics are applied externally to relieve a variety of painful conditions. NSAIDs and rubefacients are the main constituents. Alan Nathan considers the options

What's available

Non-Steroidal Anti- Inflammatory Drugs (NSAIDS)

Compounds available are: benzydamine, diclofenac, felbinac, ibuprofen and salicylic acid

How do they act?

NSAIDs exert their therapeutic action by blocking the enzyme cyclo-oxygenase, thereby preventing the formation of prostaglandins from arachidonic acid, which are produced when tissue is damaged and are major contributors to inflammation and pain. The rationale for the use of topical NSAIDs is that the drug acts directly at the affected site, avoiding the systemic adverse effects and side-effects that can result from oral administration.

This depends on the drug being absorbed sufficiently into local tissue to exert an effect, but without entering the systemic circulation. The skin presents a barrier to absorption and only a small proportion penetrates (4-25 per cent in tests conducted on ibuprofen, depending on the formulation)¹.

What are they licensed for?

Topical NSAIDs are licensed for the treatment of backache, rheumatic and muscular pain, sprains and strains, including sports injuries, and for pain relief in non-serious arthritic conditions.

Cautions

Topical NSAIDs are generally well tolerated; occasional local reactions have been reported, but these resolve on withdrawal of treatment. Products should not be applied to broken skin, lips or near the eyes. Hands should be washed after application. Topical NSAIDs should not be used with occlusive dressings. The systemic side-effects associated with oral NSAIDs are possible with topical agents, although uncommon; the risk is increased with application of large amounts.

Contraindications

Topical NSAIDs (except benzydamine) are contraindicated in patients who are sensitive to aspirin and other NSAIDs. They are not recommended for use by pregnant or breastfeeding women, or by children.

Interactions

Serum levels of NSAIDs after topical administration are low and clinically significant drug interactions are unlikely.

Presentations and dosages

Restricted to use in adults and children over 12 or 14 years (depending on brand), for up to a maximum of 7-14 days (depending on brand). Creams and gels: a 3-10cm ribbon applied in a thin layer and massaged in, up to four times a day. Sprays: 1–2ml (5–10 sprays) three or four times a day.

How effective are they?

Systematic reviews have found topical NSAIDs to be effective over short periods (up to two weeks) for chronic muscular conditions and knee and hand osteoarthritis, and to provide good levels of pain relief ^2,3. Topical NSAIDs were found to be as effective as oral NSAIDs for sprains and strains, with a very low incidence of adverse effects⁴.

Rubefacients

Most proprietary rubefacient preparations are mixtures of several ingredients, including salicylates, nicotinates and counterirritant substances from natural sources, such as turpentine oil, camphor and menthol.

How do they act?

Rubefacients are compounds that produce local vasodilation and create a sensation of warmth, exerting an analgesic effect by masking the perception of pain. Massaging greatly enhances this effect by increasing the penetration of the rubefacient into the skin and by stimulating nerve fibres that feed back messages to the brain, overriding painful stimuli.

The pressure exerted also helps to disperse local tissue pain mediators.

What are they licensed for?

Muscular and rheumatic pain, from various causes.

Contraindications

Salicylates are ingredients in many products. As well as being counter-irritants, they are hydrolysed in the skin to salicylic acid. Products containing salicylates should therefore be avoided by people who are sensitive to aspirin.

Presentations and dosages

Creams and lotions: Generally, a small amount applied with massage two to three times daily. Generally restricted in use to adults and children over 12 or 14 years, although from six years for some products.

Sprays: generally, two or three short sprays up to three times daily. Age restrictions as above.

How effective are they?

A systematic review of rubefacients containing salicylate and nicotinate esters concluded, from the best assessment of limited information, that rubefacients containing salicylates may be efficacious in acute pain and moderately to poorly efficacious in chronic arthritic and rheumatic pain⁵. The conclusions of a more recent Cochrane review were that evidence does not support the use of topical rubefacients containing salicylates for acute injuries, and in chronic conditions their efficacy compares poorly with topical NSAIDs⁶.

Other Preparations

Freeze sprays

These contain pressurised liquids that evaporate at low temperature when sprayed onto the skin, producing a loss of sensation until the nerve endings warm up again. They are most useful for treating the sharp, but short-lived, pain caused by minor knocks and sports injuries.

Menthol

Menthol has local anaesthetic and counterirritant effects. Its analgesic properties are mediated through a selective activation of k-opioid receptors.

It also triggers cold-sensitive TRPM8 receptors in the skin, producing a cooling sensation. Menthol is included in some rubefacient products and freeze sprays, alone as a gel and a patch, and combined with ibuprofen in a gel. It is also available in stick and strip form for application to the forehead for the relief of headaches and migraine.

Heat pads

• Some heat pads contain similar rubefacient ingredients to those in creams, sprays, etc, and have a counter-irritant effect.

• Disposable chemical pads act through an exothermic chemical reaction, usually catalysed oxidation of iron, and provide heat to the area of application for several hours. They are not classified as medicines.

References:

1. Hadgraft J, Whitefield M, Rosher PH. Skin penetration of topical formulations of ibuprofen 5%: an in vitro comparative study. Skin Pharmacol Appl Skin Physiol 2003;16:137–142.
2. Derry S, Moore RA, Rabbie R. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2012 Sep12;9:CD007400.
3. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. BMJ 2004;329:324–329.
4. Mason L, Moore RA, Edwards JE, et al. Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis. BMC Musculoskelet Disord 2004;19;28–35.
5. Mason L, Moore RA, Edwards JE, et al. Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain. BMJ 2004; 328:998–1001.
6. Matthews P, Derry S, Moore RA, McQuay HJ. Topical rubefacients for acute and chronic pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 3. CD007403. Product update