Topical salicylate for acute and chronic pain
Clinical bottom line
In acute conditions in three trials with 182 patients topical salicylate was significantly better than placebo with an NNT of 2.1 (1.7 to 2.8).
In chronic conditions in six trials with 429 patients topical salicylate was significantly better than placebo with an NNT of 5.3 (CI 3.6 to 10.2), but larger, more valid studies were without significant effect.
Local adverse events and withdrawals were generally rare in trials that reported them.
Background
Rubefacients are believed to work by counter-irritation, to relieve pain in the muscles, joints and tendons and in non-articular musculoskeletal conditions, rather than as NSAIDs that inhibit cyclo-oxygenase responsible for prostaglandin biosynthesis and the development of inflammation. Rubefacients are usually used as adjuvants to other therapies, such as oral analgesics, support bandages, rest, ice and compression, and may be particularly useful for patients who cannot tolerate the adverse events associated with some oral analgesics.
Reference
L Mason, RA Moore, S Derry, JE Edwards, HJ McQuay, PJ Wiffen. Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain. BMJ 2004 328: 995-998.
Systematic review
Extensive searches looked for randomised, active or placebo-controlled trials in adult patients experiencing either acute (strains, sprains and sports injuries) or chronic (arthritis, musculoskeletal) pain.
- Date review completed: March 2003
- Number of trials included: 12 trials, three of which had active controls
- Number of patients: 862
- Control groups: placebo or active controls
- Main outcomes: Clinical success, representing approximately a 50% reduction in pain, using a hierarchy of outcomes. Outcomes closest to seven days (but at least three days) were required for acute conditions, and closest to 14 days (but at least seven days) for chronic conditions.
Results
Acute pain
Three placebo controlled trials (one of low validity) had information from 182 patients. The mean percentage of patients with at least 50% pain relief was 67% with topical salicylate and was 18% with placebo. Treatment with rubefacient was significantly better than placebo with and NNT of 2.1 (1.7 to 2.8) for at least 50% pain relief at seven days in acute conditions compared with placebo (Table 1).
Table 1: Topical salicylates in acute and chronic pain
| Acute pain | ||||||
| efficacy (all trials) | 3 | 182 | 60/90 | 17/92 | 3.6 (2.4 to 5.6) | 2.1 (1.7 to 2.8) |
| local AE | 5 | 418 | 4/208 | 4/210 | 1.1 (0.4 to 3.5) | not significant |
| Chronic pain | ||||||
| efficacy (all trials) | 6 | 429† | 125/230 | 80/225 | 1.5 (1.3 to 1.9) | 5.3 (3.6 to 10.2) |
| Validity score 8 or less | 3 | 176 | 55/92 | 22/84 | 2.2 (1.5 to 3.3) | 3.0 (2.1 to 5.0) |
| Validity score 9 or more | 3 | 279 | 70/138 | 58/141 | 1.3 (0.98 to 1.6) | not significant |
Chronic pain
Six placebo controlled trials (three of low validity) had information from 403 patients (Figure 1). The mean percentage of patients with at least 50% pain relief was 54% with topical salicylate and was 36% with placebo. Treatment with rubefacient was significantly better than placebo with an NNT of 5.3 (3.6 to 10) for at least 50% pain relief at 14 days in acute conditions compared with placebo (Table 1).
Figure 1: Trials of topical salicylate in chronic pain (low validity scores blue, high validity scores yellow)
Better trials had less effect. For the three trials of higher validity, there was no difference between topical salicylate and placebo (Table 1).
Adverse events
Adverse event reporting was poor, but few were reported.
Comment
The evidence for efficacy of topical salicylates was poor. There were only two acute pain studies with decent validity scores, and only three in chronic pain. Valid chronic pain studies showed no difference between topical salicylate and placebo, while the acute pain studies could have been overturned if any negative studies emerged.