Background In skin diseases and experimental models of pruritus, pure itch is accompanied by additional sensations that are poorly characterized. Objectives This study compared the sensory qualities evoked by different models of experimentally induced pruritus including skin prick testing (SPT) with histamine or capsaicin and application of cowhage spicules. SPT as a method of capsaicin application was validated for this purpose. Methods Two pilot experiments were performed in eight healthy volunteers. First, a concentration of 8% capsaicin was identified as evoking a reproducible itch using SPT. Further, a list of the seven most frequently reported sensations was chosen after SPT with 10 mg/mL histamine, 8% capsaicin and application of 40–45 cowhage spicules. Finally, 31 subjects were challenged with the same itch‐inducers. Wheal and flare were measured at 10, 20, 40, 60 and 90 min, itch intensity every minute for 30 min, and the overall evaluation of sensory descriptors were recorded on a 100‐mm visual analogue scale once itching had subsided. Results Skin prick testing with histamine and capsaicin resulted in flare reactions, which were 23% smaller for capsaicin (P < 0.001). Histamine, capsaicin and cowhage‐induced pruritus, the duration of which was shorter for cowhage than for histamine (13.5 ± 1.4 vs. 8.8 ± 1.2 min, P = 0.005). Different mediators induced sensations of different intensities. Capsaicin produced less itch and physical urge to scratch than histamine (P = 0.001) and cowhage (P < 0.001). However, both capsaicin and cowhage induced more burning than histamine (P = 0.002 and P = 0.04, respectively). Provocation with cowhage caused more intense sensations of pricking than histamine (P = 0.033). Conclusion This study shows that provocation with histamine, capsaicin and cowhage results in itch responses that are different in their duration, the profile of accompanying sensations, and the flare that comes with the itch.

<b><i>Introduction:</i></b> Flare reactions arise due to the release of vasodilators from sensory nerves caused by antidromic transmission of action potentials after the induction of itch. <b><i>Objective:</i></b> We investigated the link between flare and itch using 3 models of itch. <b><i>Methods:</i></b> Skin provocations with histamine, capsaicin, and cowhage were performed in 31 subjects. Itch was quantified using the visual analog scale. Flare was assessed using laser speckle contrast imaging (LSCI) and digital photography. <b><i>Results:</i></b> The duration, intensity, and area under the curve of histamine-induced itch correlated with the area of increased blood flow measured with LSCI (<i>r</i> = 0.545, <i>p</i> = 0.002; <i>r</i> = 0.575, <i>p</i> = 0.001; and <i>r</i> = 0.649, <i>p</i> &#x3c; 0.001, respectively). Itch and skin blood flow in response to capsaicin or cowhage did not correlate. <b><i>Conclusion:</i></b> In histamine-induced skin inflammation, itch and increased blood flow are linked. Thus, the area of histamine-induced flare may be used as a surrogate marker for histamine-induced itch.