Topical morphine gel in the treatment of painful leg ulcers, a double-blind, placebo-controlled clinical trial: a pilot study

Abstract

Chronic painful wounds, a major health problem, have a detrimental impact on the quality of life due to associated pain. Some clinical reports have suggested that local administration of morphine could be beneficial. The aim of this study was to evaluate the analgesic effect of topically applied morphine on chronic painful leg ulcers. Twenty-one patients were randomly assigned to receive either morphine or placebo in a randomised, placebo-controlled, crossover pilot study. Each patient was treated four times in total. Pain was measured by the visual analogue score (VAS) before application of gel, directly after and after 2, 6, 12 and 24 hours. Although an overall, clinically relevant, reduction of pain was observed upon treatment with morphine, the difference was not statistically significant. Morphine reduced pain scores more than placebo on treatment occasions 1 and 2. The difference was statistically significant only 2 hours after dressing on the first treatment occasion. Thus, our study did not demonstrate a consistent and globally significant difference in nociception in patients treated with morphine. However, the relatively small number of patients included in our study and other methodological limitations makes it difficult for us to draw general conclusions regarding efficacy of topically applied morphine as an effective treatment for some painful ulcers. Further studies are warranted to evaluate the value of topically applied morphine in the treatment of patients with chronic painful leg ulcers.

Figure 1

Mean pain scores at different measurement time points for all patients. There was no statistically significant difference between placebo and morphine at any measurement time point. Data is presented as mean (of 33 observations at each measurement time point and treatment group) ± SE.

Figure 2

Comparison between morphine and placebo at different treatment occasions. Pain scores were measured before gel application, directly after and 2, 6, 12 and 24 hours after application. The dashed lines represent the mean value of measurements after application of placebo gel and the solid lines represent the mean value of measurements after application of morphine gel. The value represents a mean of two observations at each measurement time point and treatment group for all patients except patient no. 21 who had only one value for each measurement time point and treatment group. The number of patients that received morphine respective placebo were, in treatment occasion 1 (6, 11), in treatment occasion 2 (10, 7), in treatment occasion 3 (7, 9) and in treatment occasion 4 (10, 6).

Figure 3

Data represent mean visual analogue score (VAS) at different measurement time point for each patient. The value represents a mean of two observations from each measurement time point and treatment group for all patients except patient no. 21 who had only have one value for each measurement time point and treatment group.