Figure 3.

Comparison of responses to cowhage, histamine, and capsaicin. A, Venn diagram indicating incidence of response to topical cowhage and intradermal injection (10 μl) of histamine (10 μg) and capsaicin (10 μg) for 50 high-threshold, myelinated fibers tested with all three substances. Number in parentheses indicates number of fibers that were insensitive to mechanical stimuli. B, Net response during the 5 min observation period following administration of cowhage, histamine, and capsaicin to the receptive field of myelinated fibers (shaded bars) and unmyelinated fibers (open bars; median with quartiles and 5/95% percentiles). In A-fibers, the median cowhage response (184 APs/5 min) was approximately seven times larger than the median response to histamine (25APs/5 min) or capsaicin (27.5 APs/5 min) (Kruskal–Wallis ANOVA, p < 0.001, followed by multiple Mann–Whitney U tests, corrected for multiple comparisons, *p < 0.05, **p < 0.01). Within the C-fiber class, the response to cowhage was significantly larger than the response to histamine (Kruskal–Wallis ANOVA, p < 0.05, followed by Mann–Whitney U test, #p < 0.05). In A- and C-fibers, the response magnitudes to histamine and capsaicin were similar, but the cowhage response was significantly larger in A- than in C-fibers (***p < 0.001, Mann–Whitney U test). For this analysis, mechano-sensitive and -insensitive afferents were pooled, and only responders were included. C, Cowhage and histamine responses are not correlated. The magnitude of the cowhage and histamine net response in units that were tested with both pruritic stimuli did not correlate. Units responsive to either cowhage or histamine had variable response magnitudes, the cowhage responses being larger overall (note different scales on the x- and y-axes). These data suggest that different cellular signaling mechanisms are engaged by histamine and cowhage. Net response: response to active agent minus response to control; negative results were assigned zero.