Effect of Intradermal Morphine on Histaminergic and Non‐Histaminergic Itch: A Randomised, Single‐Blinded, Human Study

Itch can be a side-effect of drugs like opioids, with prevalence depending on the route of administration. This study aimed to investigate if morphine (1) induced itch and neurogenic inflammation after intradermal injection and (2) modulates the responses to locally experimentally induced histaminergic and non-histaminergic itch. Twenty-four healthy volunteers participated in this randomised, single-blinded study. Two areas on the volar forearms of each participant were randomly treated with either intradermal morphine 0.05 mL (0.1 mg/mL) or saline (isotonic saline 0.05 mL), followed by assessment of itch intensity, wheal, and flare reactions. After injection, histamine and cowhage (non-histaminergic itch) were randomly applied intradermally and topically, respectively at the sites of morphine/saline injection, and the assessments were repeated. Before saline/morphine injections (baseline measurement), after injections (post-intervention measurement), and after pruritogen application (post-pruritogen measurement), superficial blood perfusions were measured using full-field laser perfusion imaging. Morphine induced increased peak itch intensity and itch area under the curve compared to saline, without further increase by the experimentally induced histaminergic and non-histaminergic itch. Morphine also caused a larger wheal area compared to saline. Morphine increased superficial blood perfusion compared to saline both after treatment and after pruritogens. This study confirmed that (1) intradermal morphine induces spontaneous itch, (2) morphine induced neurogenic inflammation which alone and in combination with the pruritogens caused larger responses (wheal and flare) when compared with saline and (3) the itch intensities provoked by experimentally induced histaminergic and non-histaminergic substances were not modulated when applied to the morphine-treated areas.