Topical capsaicin 8% pretreatment for 24 h reduced histaminergic and nonhistaminergic itch by about 75%, while a significant reduction (≈60%) was achieved for only nonhistaminergic itch in a standard 1-h treatment. Further investigations are needed to elucidate the clinical potential of high-concentration capsaicin as an antipruritic.

Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch, are limited. Relevant preclinical and human surrogate models of non-histaminergic itch are needed to accelerate the development of novel antipruritics and diagnostic tools. Advances in basic itch research have facilitated the development of diverse models of itch and associated dysaesthesiae. While experimental itch in humans is induced over a short period of time and usually assessed psychophysically, the study of itch reactions in animals allows for both short-term and long-term studies but relies heavily on behavioural assessments. This review provides a background and a presentation of the established models of itch currently applied in animals and humans with emphasis on translatability. K E Y W O R D Sanimal, histaminergic itch, non-histaminergic itch, pruritus, surrogate models, translational ineffective. Itch and pain are related but distinct sensations, and while pain has been extensively studied, the understanding of itch transmission is lacking behind. 6 There is evidence for different peripheral and central mechanisms underlying histaminergic and non-histaminergic itch, 3,7 and elucidation of the pathways and mechanisms mediating itch, especially chronic itch, is essential to the development of novel antipruritic drugs. In this regard, both preclinical and human surrogate models serve as important tools to expand the current knowledge. 3,8This review presents an overview of the currently available preclinical and human surrogate models of itch. | APPLICABILITY OF TRANSLATIONAL MODELSIdeal translational models of pruritus should induce itch through pathways associated with those involved in human pruritic diseases while closely mimicking one or several symptomatological aspects of these diseases.For example, itch in urticaria is well linked to mast cell degranulation and can be mimicked experimentally with histamine administration in both animal and human surrogate models. 9-13 The validity is confirmed by comparable efficacy of antihistamines between the animal models, the human surrogate models and the urticarial patient population. 10-13Translational models of itch can also provide a platform for screening compounds for antipruritic activity in a preclinical setting, evaluation of antipruritic drug candidates in phase Ib, and to mechanistically profile and select patients for phase II-III clinical trials.

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