Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch

Abstract

Summary 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 25·7 ± 0·8 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 °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 41·3% at 45 °C (P < 0·01) and by 76·7% at 50 °C (P < 0·001). Cowhage‐induced itch was less prone to counterstimulation and was significantly diminished only at 50 °C, by 43·6% (P = 0·009). 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.

Mild Skin Heating Evokes Warmth Hyperknesis Selectively for Histaminergic and Serotoninergic Itch in Humans

“…It has been widely re-ported that noxious heat (i.e. ≥45°C) can inhibit and, in certain conditions, even resolve the itch sensation (3)(4)(5).…”

“…Itch was provoked by 3 different substances and methods: histamine, serotonin, and cowhage. Histaminergic itch was evoked as described previously ( 5 ). Briefly, a drop of histamine chloride (1%; Diagenics, Milton Keynes, UK) was applied in the designated area on the skin in the centre of the area and punctured with a standard skin-prick test needle (Diagenics, Milton Keynes, UK).…”

“…Cowhage-induced itch was evoked by application of 35–40 cowhage spicules on the skin; as described previously ( 5 , 24 , 25 ).…”

“…In recent years, studies have focused on the relationship between heat and itch, and shown that heat in the noxious range can inhibit experimentally evoked itch to various degrees (3)(4)(5). Unfortunately, applying heat in the noxious range (> approximately 45°C) as a treatment modality is not a feasible solution, due to the potential skin damage that prolonged exposure may cause.…”

Heat stimulation as a modulatory tool for the histaminergic and non-histaminergic itch

“…Histamine has to be introduced into the skin, to achieve an itch sensation. This can be done using a skin prick test, iontophoresis, intradermal injection and inactivated cowhage spicules soaked in a histamine solution 50,52,[73][74][75][76] . Another itch human model is achieved by the use of cowhage spicules already characterized in 1955 77,78 .…”