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

Abstract

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: https://www.clinicaltrialsregister.eu/ctr-search/search

The Impact of Diclofenac Gel on Ion Transport in the Rabbit (Oryctolagus cuniculus) Skin: An In Vitro Study

“…The ability to respond to stimuli both from the inside of the body and the external environment is closely correlated with changes in the transport of ions, especially sodium and chloride ions [ 17 , 22 ]. It has been proven that the constant transportation of water and sodium, chloride and potassium ions are associated with the sensory system and the initiation of hypersensitivity and/or allergy reactions [ 3 , 4 , 5 ]. Changes in the directed transport of water and ions can be associated with the formation of micro-deformations and sites with changed water content along with the sensation reactions, e.g., pain or development of pain hypersensitivity [ 18 , 19 , 20 , 21 , 23 , 29 ].…”

“…NSAIDs, including diclofenac, act by inhibiting COX-1 and COX-2, thereby blocking the formation of prostaglandins and thromboxanes in the dermis cells, which are involved in the formation of the inflammatory reaction, fever, and pain transmission [ 5 , 36 ]. The form in which the drug is taken significantly affects the rate and amount of the active substance absorbed into the subcutaneous tissue.…”

“…Moreover, COX-2 is an enzyme whose activity increases rapidly in inflamed tissues [ 4 ]. As a drug, diclofenac is characterized by anti-inflammatory, antipyretic, analgesic, and platelet aggregation-inhibiting effects, although in this case, it has a weaker and shorter duration than acetylsalicylic acid [ 1 , 2 , 4 , 5 ].…”

“…Considering its action, diclofenac can be used in degenerative joint disease, long-term inflammations, such as spondylitis, painful menstruation, and after surgery [ 5 , 6 , 7 ]. Moreover, some studies have shown that, in addition to arthritis and pain, the COX-2 inhibitors such as diclofenac can be used to treat neurodegenerative diseases, including Alzheimer’s disease [ 8 , 9 ], and to reduce the risk of many cancers [ 10 , 11 , 12 ].…”

Testing Topical Products Specifically to Reduce Inflammatory Pain from Gout: Transdermal NSAID Delivery and Monosodium Urate Solubility

“… 7 , 8 In a recent paper by Pradal, 7 it is suggested that the higher potency of diclofenac would result in a significantly higher values of “modified index of anti-inflammatory activity” for the diclofenac products in-spite of the lower permeation rates versus ibuprofen (around 10 fold increase for diclofenac). However, another recent paper by Wade et al 14 compared 1% diclofenac gel with 5% ibuprofen gel and 5% ibuprofen/3% menthol gel in a clinical trial. In this trial there is only a small improvement in delivered pain relief for the diclofenac product over the ibuprofen gel.…”