Screening Topical Antipruritics: A Histamine-Induced Itch Human Model

Abstract

Itch is a subjective symptom; its magnitude (intensity) may be only estimated by the reports of patients or volunteers. We utilized a comparative screening method to identify and quantify the efficacy of topical antipruritics with a histamine-induced itch human model. Ten individuals responsive to histamine-induced itch sensation were enrolled. Both forearms served as test sites. Each test site was treated randomly either by histamine injection only or pretreated with a coded candidate formula for 30 min and then a histamine injection. Itch was experimentally induced in each test site by the intracutaneous injection of 100 microg histamine dihydrochloride dissolved in 1 ml normal saline. Itch magnitude was measured each minute after histamine injection for 20 min with a magnitude visual analogue scale. Itch duration was also recorded. Formulation D significantly (p < 0.05) decreased itch magnitude (within a 20-min test period), from 2.6 +/- 2.1 cm (mean +/- SD) to 2.2 +/- 2.1 cm (mean +/- SD) when compared to its vehicle control; it also significantly (p < 0.05) shortened itch duration (15.0 +/- 7.4 min; mean +/- SD) in comparison with its vehicle control (20.3 +/- 7.0 min; mean +/- SD). Of all the formulations tested, formulation D was the most effective antipruritic in decreasing histamine-induced itch. This method may act as a simple and robust screening procedure when evaluating potential antipruritics and allow a comparison among products. Until validated with disease-induced itch, e.g., atopic dermatitis, the model should be considered screening in nature.