Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain
BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.38040.607141.EE (Published 22 April 2004) Cite this as: BMJ 2004;328:995Data supplement
Table A Studies excluded from rubefacient systematic review
Table B Characteristics of included studies
Forrest plots of efficacy analyses
Search strategy for RCTs of rubefacients [as supplied by authors]
#1 randomised control trial (MeSH term)
#2 random* OR blind OR double-blind OR double-masked OR masked OR trial
#3 #1 OR #2
#4 administration, topical (MeSH term)
#5 topical* OR cutaneous OR dermal OR transcutaneous OR transdermal OR percutaneous OR skin OR massage OR embrocation OR gel OR ointment OR aerosol OR cream OR crème OR lotion OR mouse OR foam OR liniment OR spray OR rub OR balm OR salve OR emulsion OR oil OR patch OR plaster
#6 #4 OR #5
#7 athletic injuries (MeSH) OR musculoskeletal diseases (MeSH)
#8 pain* OR analgesi* or strain OR sprain* OR "sports injury" or arthrit* OR rhemat* or osteoarth* OR tend?nitis OR sciatica OR lumbago OR fibrositis
#9 #7 OR #8
#10 irritants (MeSH)
#11 rubefacient OR "counter-irritant" OR "ammonium salicylate" OR "radian B" OR "benzyl nicotinate" OR kausalpunkt OR pykaryl OR rubriment OR "bornyl salicylate" OR camphor OR "choline salicylate" OR "diethylamine salicylate" OR algesal OR algoderm OR algoflex OR artogota OR "Lloyd’s cream" OR physiogesic OR rheumagel OR "transvasin heat spray" OR "diethyl salicylate" OR "ethyl nicotinate" OR mucotherm OR transvasin "PR heat spray" OR "ethyl salicylate" OR "glycol monosalicylate" OR ralgex OR salonpas OR intralgin OR "glycol salicylate" OR "algipan rub" OR meclofenamic OR menthol OR "methyl butetisalicylate" OR doloderm OR "methyl gentisate" OR "methyl nicotinate" OR "nella red oil" OR wintergreen OR "sweet birch oil" OR "methyl salicylate" OR aezodent OR argesic OR aspellin OR balmosa OR "bengue’s balsam" OR "chymol emollient balm" OR " deep heat" OR dencorub OR dermacreme OR dubam OR eftab OR exocaine OR germolene OR "gone balm" OR gordogesic OR linsal OR salonpas OR intralgin OR mentholatum OR monophytol OR nasciodine OR phlogont rheuma OR "PR heat spray" OR ralgex OR rheumabad OR rheumax OR salonair OR thermo-rub OR nicoboxil OR finalgon OR ortholan OR nonivamide OR Warme-Pflaster OR picolamine OR salicylate OR algiospray OR reflex OR "propyl nicotinate" OR elacur OR nicodan OR salicylamide OR isosal OR salicylate OR salycilic OR movelat OR radian OR "thurfyl salicylate" OR triethanolamine salicyalte" OR "analgesia crème" OR antiphlogistine OR aspercreme OR Ben-Gay OR bexidermil OR dencorub OR exocaine OR metsal OR miosal OR mobisyl OR myoflex OR pro-gesic OR royflex OR sportscreme OR topicrem
#12 #10 OR #11
#14 (#3 AND #6 AND #9 AND #12)
Hierarchy of outcomes in order of preference
1) Number of patients with a 50% or more reduction in pain (if given)
2) Patient reported global assessment of treatment
3) Pain on movement
4) Pain on rest or spontaneous pain
5) Physician or investigator global assessment of treatment
Table A [as supplied by authors] Studies excluded from rubefacient systematic review
Reference Reason for exclusion Cohen M, Wolfe R, Mai T, Lewis D. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol 2003;30:523-52. no usable data & not rubefacient Crielaard JM, Franchimont P. [Value of using Reparil-gel in sports traumatology]. Acta Belg Med Phys 1986;9:287-98. not RCT Dettoni A, Olivero C, Sibelli P. [Activity of the combination of escin, heparin sodium and diethylamine-salicylate as compared with the activity of the single components in minor traumatology]. G Clin Med 1982;63:279-83. cannot extrapolate data Dragani L, Colozzi A, Schiavone C et al. [A heparin-glucuronylglucosaminoglycan combination for topical use. An evaluation of the therapeutic effects in induced experimental muscle damage and in minor sports injuries]. Minerva Med 1989;80:397-403. no extractable data Dragani L, Giamberardino MA, D’Aurelio A, Formica LM, Colozzi A, Tamburro P. [Evaluation of reduction of NSAID consumption after local treatment with a heparin-heparinoid combination in patients with osteoarthritis]. Riv Eur Sci Med Farmacol 1990;12:283-95. no extractable data Howell T. Relief of rheumatic pains with diethylamine salicylate cream: a clinical trial. Brit J Phys Med 1955;18:62-3. not randomised Jolley HM, Torneck CD, Siegel I. A topical choline salicylate gel for control of pain and inflammation in oral conditions-a controlled study. J Can Dent Assoc 1972;2:72-4. oral condition Kantor TG, Altman RD. Assessment of topical agents for the pain of osteoarthritis of the hand. Pain 1990;supp5:Ab S54. too short duration Kleinschmidt Von J, Lührs M, Drexel H. [The valuation of the therapetic results obtained with mobilat gel applied cutaneously in a double blind study]. Fortschr Med 1975; 93(19):986-90. quasi-randomised Koll R, Buhr M, Dieter R, Pabst H, Predel HG, Petrowicz O, Gianetti B, Wagener S. [Efficacy and tolerability of comfrey extract (Extr. Rd. Symphyti) in ankle distortions: Results of a multi-centre, randomised, placebo-controlled double-blind study]. Zeitschrift für Phytotherapie 2000;21:127-34. not rubefacient Pabst H, Segesser B, Bulitta M, Wetzel D, Bertram S. Efficacy and tolerability of escin/diethylamine salicylate combination gels in patients with blunt injuries of the extremities. Int J Sports Med 2001;22(6):430-6. too short duration Pasila M, Visuri T, Sundholm A. Recovery of recent ankle sprains:A comparison between the value of the Movelat and its base cream. Rheumatol rehabil 1980;19:256-57. no usable data Von Batky ES. [The treatment of sport and accident injuries with a new gel preparation]. Z Allgemeinmed 1971;47(25):1281-2. not RCT Weisinger E, Singh S, Doyle JL. Analysis of purported rubefacient qualities in a new toothpaste. J N J Dent Assoc 1970;42:24-5. oral condition & not RCT Wetzel D, Menke W, Dieter R, Smasal V, Giannetti B, Bulitta M. Escin/diethylammonium salicylate/heparin combination gels for the topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study. Br J Sports Med 2002;36(3):183-8. too short duration
Table B [as supplied by authors] Characteristics of included studies
Forrest plots of efficacy analyses [as supplied by author]
Acute conditions
Chronic conditions
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