Sensory responses to injection and punctate application of capsaicin and histamine to the skin

Abstract

A punctate, cutaneous application of capsaicin or histamine by means of a cowhage spicule elicits itch accompanied by pricking/stinging, burning, and typically, one or more areas of dysesthesia (alloknesis, hyperalgesia, hyperknesis). When applied over a wider and deeper area of skin by means of intradermal injection, histamine evokes the same sensory effects, but capsaicin evokes pain and hyperalgesia with allodynia instead of alloknesis. To examine the sensory effects of the spatial spread, depth, and amount of capsaicin and histamine, we applied different amounts of capsaicin or histamine by intradermal injection or by single vs multiple spicules within a circular cutaneous region of ~5 mm. Subjects rated the perceived intensity of itch, pricking/stinging, and burning for 20 minutes. Histamine injections or multiple spicules of capsaicin or histamine that resulted in a greater area of flare than a single spicule of each chemical evoked no greater magnitudes of sensation or areas of dysesthesia. Capsaicin injections elicited a dose-dependent increase in the magnitude of nociceptive sensations, areas of dysesthesia, and flare. However, there was little or no itch; and allodynia replaced alloknesis. Yet, hyperalgesia was typically accompanied by hyperknesis. We conclude that the pruritic sensory responses produced by capsaicin/histamine spicules and histamine injections may be due to activation of common nerve fibers, possibly different from those mediating the flare, and that capsaicin injections may activate additional fibers whose effects mask the sensory effects of fibers mediating itch and alloknesis but not hyperknesis.

Figure 1

Time course of the perceived intensity of itch and nociceptive sensations evoked by single vs. multiple spicules containing capsaicin or histamine. A-F, The mean ratings of itch, pricking/stinging and burning obtained from 10 subjects are plotted for successive intervals of 30 s after spicule application. For clarity, the SEM is plotted every 5 min starting with the peak rating for each quality. On the right vertical axis, the locations of 3 of the verbal descriptors are shown in correspondence with the ratings of perceived intensity indicated on the left vertical axis (see section 2.7 for further details).

Figure 2

The areas of dysesthesia evoked by single vs. multiple spicules containing capsaicin or histamine. A, Typical areas of dysesthesias evoked by single and multiple capsaicin spicules in a subject. B-D, The mean areas of alloknesis, hyperknesis, and hyperalgesia evoked by each chemical delivered in single vs. multiple spicules.

Figure 3

Areas of wheal and flare produced by single vs. multiple spicules of capsaicin or histamine. Typical areas of wheal or flare accompanying the sensations evoked by single vs. multiple spicules of capsaicin (A) and histamine (B) in a subject. Unlike histamine, capsaicin did not elicit a wheal. C, The mean area of wheal was significantly greater for multiple than a single spicule of histamine. D, The mean area of flare evoked by histamine or capsaicin was significantly larger for multiple spicules than for the single spicule.

Figure 4

Time course of the perceived intensity of itch and nociceptive sensations evoked by different concentrations of injected capsaicin or histamine. Mean ratings of the perceived intensity of itch, pricking/stinging and burning obtained from 15 subjects are plotted for successive intervals of 30 s after injection. The inset in panel A indicates the amount of chemical injected corresponding to each curve in the figure. The SEM is plotted every 5 min starting with the peak rating for each quality. On the right vertical axis, the locations of 4 of the verbal descriptors are shown in correspondence with the numerical ratings of perceived intensity indicated on the left vertical axis.

Figure 5

Comparison of the perceived intensity of itch and nociceptive sensations produced by histamine, capsaicin, and heat. For applications of capsaicin (A) and histamine (B), the mean peak magnitude of itch, pricking/stinging, and burning (I, P, and B, respectively) are plotted separately for the responses to a single spicule (shown as histograms) and the responses to differing amounts injected. C: Mean perceived intensity of each sensory quality evoked by heat stimulus of 5 s duration at different temperatures. The dashed horizontal line indicates that the mean perceived intensity of itch did not exceed a rating of moderate whereas nociceptive sensations approached or exceeded ratings of “strong” in response to the higher amounts of capsaicin or temperature of heat.