Antipruritic Effects of Transient Heat Stimulation on Histaminergic and Nonhistaminergic Itch.

Background Chronic itch is notoriously difficult to treat. Counterstimuli are able to inhibit itch, but this principle is difficult to apply in clinical practice, and the mechanisms behind counterstimulation-induced itch suppression in humans are unclear. Objectives Firstly, to analyse the stimulus-response effects of transient heat stimuli on histaminergic and nonhistaminergic itch, and secondly, to investigate whether the antipruritic effect depends on homotopic (peripheral mediation) or heterotopic (central mediation) counterstimulation relative to the itch provocation site. Methods Eighteen healthy volunteers participated (eight female, mean age 25 center dot 7 +/- 0 center dot 8 years). Itch was evoked on premarked areas of the volar forearms, by either histamine (1% solution) or cowhage (35-40 spicules). In addition to the itch provocations (experiment 1), 5-s homotopic heat stimuli at 32, 40, 45 or 50 degrees C were applied. In experiment 2, heat stimuli were applied either homotopically, intrasegmentally (next to the provocation site) or extrasegmentally (dorsal forearm). Itch intensity was evaluated throughout the procedures using a digital visual analogue scale. Results Homotopic counterstimuli inhibited histaminergic itch by 41 center dot 3% at 45 degrees C (P < 0 center dot 01) and by 76 center dot 7% at 50 degrees C (P < 0 center dot 001). Cowhage-induced itch was less prone to counterstimulation and was significantly diminished only at 50 degrees C, by 43 center dot 6% (P = 0 center dot 009). Counterstimulations applied heterotopically were not able to inhibit itch significantly. Conclusions Itch pathway-specific effects of counterstimuli were observed between homo- and heterotopic stimulation. Histaminergic itch was robustly inhibited by short-term homotopic noxious heat stimuli for up to 10 min. Nonhistaminergic itch was only weakly inhibited. The inhibitory effects exerted by the short-term heat stimuli only occurred following homotopic counterstimulation.