title: Salicylate-containing rubefacients for acute and chronic musculoskeletal pain in adults.
abstract: BACKGROUND
  Rubefacients containing salicylates cause irritation of the skin and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. This is an update of a review of rubefacients for acute and chronic pain, originally published in 2009, which found limited evidence for efficacy.
  
  
  OBJECTIVE
  To assess the efficacy and safety of topically applied salicylates in acute and chronic musculoskeletal pain in adults.
  
  
  METHODS
  We searched CENTRAL, MEDLINE, and EMBASE, from inception to 22 August 2014, together with the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of included studies and relevant reviews.
  
  
  METHODS
  Randomised, double-blind, placebo- or active-controlled clinical trials of topical rubefacients containing salicylates to treat musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions.
  
  
  METHODS
  Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. We calculated risk ratio (RR) and number needed to treat to benefit or harm (NNT or NNH) with 95% confidence intervals (CI) using a fixed-effect model. We analysed acute and chronic conditions separately.
  
  
  RESULTS
  New searches for this update identified one new study that satisfied our inclusion criteria, although it contributed information only for withdrawals. Six placebo- and one active-controlled studies (560 and 137 participants, respectively) in acute pain, and seven placebo- and three active-controlled studies (489 and 182 participants, respectively) in chronic pain were included in the review. All studies were potentially at risk of bias, and there were substantial differences between studies in terms of the participants (for example the level of baseline pain), the treatments (different salicylates combined with various other potentially active ingredients), and the methods (for example the outcomes reported). Not all of the studies contributed usable information for all of the outcomes sought.For the primary outcome of clinical success at seven days in acute conditions (mostly sprains, strains, and acute low back pain), the RR was 1.9 (95% CI 1.5 to 2.5) and the NNT was 3.2 (2.4 to 4.9) for salicylates compared with placebo, but this result was not robust (very low quality evidence). Using a random-effects model for analysis the RR was 2.7 (1.05 to 7.0). For the same outcome in chronic conditions (mostly osteoarthritis, bursitis, and chronic back pain), the RR was 1.6 (1.2 to 2.0) and the NNT was 6.2 (4.0 to 13) (very low quality evidence). This result was not substantially changed using a random-effects model for analysis. In both categories there were a number of factors might have influenced the results but sensitivity analysis was limited because of the small number of studies and participants.For both acute and chronic painful conditions any evidence of efficacy came from the older, smaller studies, while the larger, more recent studies showed no effect.Adverse events were more common with salicylate than with placebo but most of the events occurred in only two studies. There was no difference when these studies were removed from the analysis (very low quality evidence). Local adverse events (at the application site) were again more common with salicylate but were nearly all in one study (in which salicylate was combined with another irritant). There was no difference when this study was removed (very low quality evidence).There were insufficient data to draw conclusions against active controls.
  
  
  CONCLUSIONS
  The evidence does not support the use of topical rubefacients containing salicylates for acute injuries or chronic conditions. They seem to be relatively well tolerated in the short-term, based on limited data. The amount and quality of the available data mean that uncertainty remains about the effects of salicylate-containing rubefacients.
authors.affiliation: Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.
authors.forename: Sheena
authors.initials: S
authors.lastname: Derry
authors.forename: Paul R L
authors.initials: PR
authors.lastname: Matthews
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Wiffen
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Moore
mesh_terms: D000208:Acute Disease; D000287:Administration, Topical; D000328:Adult; D002908:Chronic Disease; D006801:Humans; D007509:Irritants / Q000008:administration & dosage* / Q000009:adverse effects; D059352:Musculoskeletal Pain / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012459:Salicylates / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007509:Irritants; D012459:Salicylates