Correlations between histamine-induced wheal, flare and itch.

Correlations between the skin reactions wheal and flare and the subjectively reported degree of itch were investigated in response to 1% histamine, intradermally applied by standardized skin prick and by iontophoresis. Experiments were performed with 15 male volunteers using a threefold repeated measures design (skin prick, and iontophoresis with 0.13 mA for 10 s and with 2.0 mA for 10 s). Skin reactions (perpendicular diameters) were determined at the time of their maximum (10 min). Itch was rated on a computerized visual analogue scale which was anchored upon the individual scratch threshold. Most effective in producing itch was the skin prick which caused strong sensations markedly above the scratch threshold during the entire period of measurement (30 min), whereas iontophoresis induced only transient itch sensations. On the other hand, the largest wheals were generated by iontophoresis of both intensities (mean 10 or 14 mm vs 6 mm with skin prick). The higher current induced higher itch, wheal and flare responses, but after eliminating this effect of stimulus intensity, no correlations were found. In contrast, skin prick-induced flare reactions varied with the degree of itch above the scratch threshold (r = 0.56; P < 0.01). Repeated measurements showed a higher stability for the itch reaction with skin prick compared with iontophoresis. It is hypothesized that in iontophoresis the brief (10-s) histamine bolus passed the most superficial pruritoceptive C fibres too quickly to induce long-lasting itch sensations, whereas the skin prick caused a deposit at the dermal-epidermal junction releasing histamine during the entire time of measurement. Consequently, both the C fibre-mediated itch and the axon reflex flare were more pronounced with the skin prick, and the wheal resulting from a permeability increase in the postcapillary venule walls was an independent phenomenon.