Human surrogate models of histaminergic and non-histaminergic itch

Within the last decade understanding of the mechanistic basis of itch has improved significantly, resulting in the development of several human surrogate models of itch and related dysesthetic states. Well-characterized somatosensory models are useful in basic studies in healthy volunteers, in clinical studies for diagnostic and segmentation purposes, and in pharmacological studies to evaluate the antipruritic efficacy of existing and novel compounds. This review outlines recently introduced histamine-independent human models of itch, their mechanisms, their ability to induce clinically relevant phenomena, such as alloknesis, and the results obtained through their use. The article also introduces recent advances in the understanding of itch and provides an overview of the methods to assess experimentally-induced itch and associated manifestations. Major improvements are warranted in the treatment of chronic pruritus, and reliable human surrogate models are a valuable tool in achieving them, both for basic researchers and for clinicians.