The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model - A Randomized, Placebo-controlled Trial

Pain involves responses in which both peripheral and central mechanisms contribute to the generation of pain. Pre-clinical laboratory data have supported that a topical formulation of combined diclofenac and methadone (Diclometh) may alleviate local pain, and potentially the side effect profile should be low. We hypothesized that anti-allodynic and anti-hyperalgesic effects of Diclometh could be demonstrated in a human experimental pain model, and that Diclometh would be safe to administer. Thus, the aims were: 1) To compare two doses of Diclometh versus placebo; 2) To assess the safety profile of Diclometh. The study was a cross-over, randomized, double-blind, placebo-controlled comparison of two doses of Diclometh gel (0.1% and 0.2%) administered topically in healthy participants. Nerve growth factor (NGF) and capsaicin intradermal injections were used as human pain models. Pressure stimulation, contact heat stimulation, hyperalgesia (pin-prick stimulation) and allodynia (brush stimulation) to mechanical stimulation were performed in the area where capsaicin and NGF were injected. Side effects were recorded on a four-point Likert scale. Twenty-one men completed the study (mean age 26.14±5.3). Diclometh 0.2% reduced the capsaicin-induced dynamic mechanical allodynia compared to placebo (primary endpoint, P=0.03). No other primary or secondary endpoints were found significantly different (all P>0.05). All side effects were reported as mild with no differences between treatments (P=0.15) Indication of anti-allodynic effect of Diclometh 0.2% was found. Additionally, it was demonstrated that Diclometh was safe to use. This article is protected by copyright. All rights reserved.