Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial

Abstract

PurposeThis study was performed to evaluate topical 1% diclofenac/3% menthol gel in treating ankle sprain.DesignIn this randomized, double-blind, placebo-controlled trial, adolescents and adults with acute ankle sprain (N = 385) applied 4 g of gel containing 1% diclofenac/3% menthol (n = 117), 1% diclofenac (n = 112), 3% menthol (n = 77), or placebo (n = 75) four times daily. The primary outcome was the area under the curve of pain intensity (PI) on movement [0 (no pain) to 10 (extreme pain)] from 24 to 72 hours post-application (AUC1–3 days). Secondary outcomes included pain relief (PR); PI; time to onset of PR, meaningful PR, cooling, and complete recovery; PI difference; sum of PI difference; total PR; reduction in ankle swelling; and the patient’s global assessment of response to treatment.ResultsThere were no statistically significant differences in AUC1–3 between 1% diclofenac/3% menthol and placebo, diclofenac, or menthol gels and no meaningful advantages of 1% diclofenac/3% menthol for any secondary outcome. There was a higher incidence of skin and application-site events with 1% diclofenac/3% menthol than with placebo or 1% diclofenac.ConclusionNo significant improvement was observed with topical 1% diclofenac/3% menthol gel compared with placebo, 1% diclofenac, or 3% menthol gel in treating pain from ankle sprain.ClinicalTrials.Gov Identifier: NCT02100670

Comparison of diclofenac gel, ibuprofen gel, and ibuprofen gel with levomenthol for the topical treatment of pain associated with musculoskeletal injuries

“…Lai et al. (2017) 2 used four-times-daily treatment with 1% diclofenac/3% menthol gel in adolescents and adults with acute ankle sprain. They measured the area under the curve of pain intensity on movement from 24 to 72 hours post-application using an 11-point NRS for pain and found no significant improvement compared with placebo, 1% diclofenac, or 3% menthol gel.…”

“…1 Topical menthol, which stimulates thermoreceptors, has also been used to enhance the efficacy of analgesic gels containing NSAIDs. 2 The focus of the present study was to assess the effect of adding levomenthol, a form of topical menthol, to an ibuprofen gel.…”

“…7,8 Following topical application, menthol stimulates thermoreceptors to generate cold or warm sensations, and has an anaesthetic effect. 2,9,10 Menthol can also enhance the skin penetration of topical analgesics and may increase their effectiveness in relieving pain. 2 In addition, many topical analgesic treatments are formulated in an aqueous/alcoholic gel, and this preparation has a soothing and rapid cooling effect when applied to the skin.…”

Role of phytochemicals as nutraceuticals for cognitive functions affected in ageing

“…Monoterpenes have been shown as neuroactive in a range of studies relevant to cognition and AD (Okello & Howes, ; also see Table ). Two monoterpenes (used in mainstream medicine for topical analgesia) are menthol (Lai, Collaku, & Reed, ) and borneol (the latter occurs in cinnamon [ Cinnamomum species] resin at 96%), which act via the transient receptor potential melenastatin (TRPM8; Wang et al, ). The clinical improvements in memory seen by Lamiaceae species are likely due to the polypharmacology of constituents (referred to above).…”

“…Monoterpenes have been shown as neuroactive in a range of studies relevant to cognition and AD ; also see Table 1). Two monoterpenes (used in mainstream medicine for topical analgesia) are menthol (Lai, Collaku, & Reed, 2017) and Bacopa (Bacopa monnieri) is a plant food used in salads and dahls, and as an Ayurvedic medicine used for memory. In an RCT meta-analysis, it improved cognition, attention and memory in child, adolescent, adult, and elderly populations and improved memory in multi-task stress activities and in pilot trials for mild cognitive impairment (Downey et al, 2013;Howes & Houghton, 2012;Kongkeaw, Dilokthornsakul, Thanarangsarit, Limpeanchob, & Norman, 2014).…”