Topical Morphine for Oral Mucositis in Children: Dose Finding and Absorption

Abstract Context Systemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors are upregulated during inflammation, for example, in oral mucositis. Objectives The aims of this study were to investigate the dose-response relationship ( n =7) and the potential absorption of topical morphine ( n =5) across oral mucosa in children with oral mucositis. Methods The dose-response study was conducted according to a sequential study design (Dixon's Up-and-Down method) for topical morphine doses of 0.025–0.400mg/kg, with the decrease in oral pain score as the primary outcome. To assess potential absorption across oral mucosa after a single dose of topical morphine of 0.050mg/kg, blood samples were drawn and the plasma concentrations of morphine and metabolites were determined by high-pressure liquid chromatography. Results A decrease in oral pain score of ≥36% was achieved in six of seven patients in the dose-response part of the study. Plasma concentrations of morphine and metabolites were well below effective analgesic levels. Conclusion No obvious dose-response effect was found for topical morphine doses of 0.025–0.400mg/kg, and topically applied morphine was not absorbed in clinically relevant doses. However, this study was limited by the small number of patients and the allowance of a systemic opioid as rescue medication. Thus, randomized controlled studies are needed to further investigate the analgesic properties of topical morphine.