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

J Int Med Res. 2019 Sep;47(9):4454-4468. doi: 10.1177/0300060519859146. Epub 2019 Jul 29.


Objective: To determine whether 3% w/w levomenthol added to ibuprofen gel (5% w/w) improves its efficacy compared with ibuprofen gel alone or diclofenac gel (1.16%) for the treatment of soft-tissue injuries.

Methods: A total of 182 patients with acute soft-tissue injuries participated in a randomised, single-blind, single-dose study to assess the efficacy and safety of three topical analgesic gels. Efficacy was assessed as the score change in a numeric rating scale for pain.

Results: The median time to significant pain relief was 20 minutes for the ibuprofen/levomenthol and diclofenac gels but 25 minutes for ibuprofen gel. At 2 hours, significantly more patients treated with ibuprofen/levomenthol gel reported a cooling sensation (45.8%) compared with diclofenac (16.4%) or ibuprofen (14.7%) gels, and both ibuprofen/levomenthol and diclofenac gels provided significantly more effective global pain relief compared with ibuprofen gel. Few adverse events and no serious adverse events related to study medication were recorded.

Conclusions: Although all gels effectively relieved pain, both ibuprofen/levomenthol and diclofenac gels provided superior global pain relief compared with ibuprofen gel, with a shorter median time to significant pain relief. Only ibuprofen/levomenthol gel provided cooling for up to 2 hours. None of the gels were associated with serious safety concerns. EudraCT No 2015-005240-33 EU Clinical Trials Register URL:

Keywords: Analgesic; diclofenac; ibuprofen; levomenthol; menthol; pain relief; topical.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Adolescent
  • Adult
  • Aged
  • Diclofenac / adverse effects
  • Diclofenac / therapeutic use*
  • Female
  • Gels / administration & dosage*
  • Humans
  • Ibuprofen / adverse effects
  • Ibuprofen / therapeutic use*
  • Male
  • Menthol / administration & dosage
  • Menthol / adverse effects
  • Menthol / therapeutic use*
  • Middle Aged
  • Musculoskeletal System / injuries*
  • Pain / drug therapy*
  • Survival Analysis
  • Young Adult


  • Gels
  • Diclofenac
  • Menthol
  • Ibuprofen