Nalbuphine is a dual-acting ƙ-agonist/µ-antagonist opioid that is thought to exert an antipruritic effect by regulating imbalances that can exacerbate itch. The purpose of this study was to evaluate the effect of nalbuphine for attenuating itch using an established preclinical animal model. The substance P (subP)–induced mouse itch model has been previously used to simulate antihistamine-resistant pruritus observed in patients with various dermatoses. Nalbuphine was tested using a vehicle control and nalfurafine as a positive comparative control (PCC). Nalbuphine was tested at doses that were shown in initial phases of this study to have no effect on spontaneous motor function, to ensure that the potential effect on scratching behavior would not be confounded by overall sedation. Mice were pretreated with vehicle, PCC (0.01 or 0.02 mg/kg), or nalbuphine (10 mg/kg or 30 mg/kg) and video recorded in individually housed plexiglass cages for 30 min to establish baseline scratching. The mice were then challenged with vehicle or subP (250 ng/0.05 mL) and recorded for an additional 30–60 min. Scratching scores were calculated using 2 independent raters trained prior to the study and blinded to the dosing scheme. Scratches to the injection site (upper right shoulder) with hind paws were counted; continuous scratching over 1 second was counted as 1 scratch. Nalbuphine pretreatment resulted in a significant reduction in scratching at both tested doses: 10 mg/kg: 43% reduction (107 to 61 scratches; P<0.001); 30 mg/kg: 51% reduction (107 to 52; P<0.001). Although there was an apparent dose-response effect, there was no statistical difference between the tested nalbuphine doses. An equivalent suppression in scratching activity was observed between nalbuphine and the PCC, supporting the hypothesis that nalbuphine may be capable of reducing the sensation of itch in humans. In conclusion, the effects of nalbuphine on this subP–induced mouse itch model suggest that nalbuphine may be a potential therapy for pruritic conditions.

ESDRLB026 - Nalbuphine in the Attenuation of Substance P–Induced Itch in Mice

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING