Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage

Abstract

Itch evoked by cowhage or histamine is reduced or blocked by capsaicin desensitization, suggesting that pruriceptive neurons are capsaicin-sensitive. Topical capsaicin can evoke both nociceptive sensations and itch, whereas intradermal injection of capsaicin evokes only burning pain. To dissociate the pruritic and nociceptive sensory effects caused by the chemical activation of sensory neurons, chemicals were applied in a punctiform manner to the skin of the forearm using individual, heat-inactivated cowhage spicules treated with various concentrations of capsaicin (1-200 mg/ml) or histamine (0.01-100 mg/ml). Perceived intensities of itch, pricking/stinging and burning were obtained every 30 s using the general version of the Labeled Magnitude Scale and compared with ratings evoked by individual native cowhage spicules. Similar to cowhage, capsaicin and histamine spicules reliably evoked sensations of itch in a dose-dependent manner which were most often accompanied by pricking/stinging and to a lesser extent burning. Spicules containing 200 mg/ml capsaicin or 10 mg/ml histamine yielded peak magnitudes and durations of sensations comparable to those elicited by cowhage. Each type of spicule also produced comparable areas of dysesthesias (enhanced mechanically evoked itch or pain) and/or skin reactions (wheal and/or flare) in surrounding skin, though inconsistently. The incidence of flare was greater in response to histamine than to capsaicin or cowhage. These results suggest the possibility that capsaicin, histamine and cowhage activate common peripheral or central neural mechanisms that mediate pruritic sensations and associated dysesthesias.

Fig. 1

Time course of the perceived intensity of itch and nociceptive sensations evoked by different concentrations of capsaicin. Mean ratings of the perceived intensity of itch (A), pricking/stinging (B), and burning (C) were obtained at successive intervals of 30 sec in response to the indicated concentrations of capsaicin.

Fig. 2

Effects of the concentration of capsaicin on the magnitude and duration of itch and pricking/stinging. Linear regressions for logarithmic (Lg) values of concentration and the peak magnitude (“Lg peak mag”), duration (Lg duration in minutes, m), and area under the rating curve (Lg AUC) for itch (A, B, and C, respectively) and pricking/stinging (D, E, and F). Dashed lines provide 95% confidence limits. The slope of each line was significantly different from zero (see main text). Significant slopes were not obtained for burning (data not shown).

Fig. 3

Time course of the perceived intensity of itch and nociceptive sensations evoked by a spicule containing different concentrations of histamine. Mean ratings of the perceived intensity of itch (A), pricking/stinging, (B) and burning (C) were obtained at successive intervals of 30 sec in response to each indicated dose of histamine.

Fig. 4

Effects of the concentration of histamine on the magnitude and duration of itch, pricking/stinging, and burning. Linear regressions for logarithmic (Lg) histamine concentrations and logarithmic (Lg) values of the mean peak magnitude (“Lg peak mag”), duration (“Lg duration” in minutes, m), and AUC (Lg AUC) for itch (A, B, and C, respectively), pricking/stinging (D, E, and F), and burning. With the exception of the duration of burning, the slope of each line was significantly different from zero (see main text).

Fig. 5

Comparison of itch and nociceptive sensations evoked by capsaicin, histamine and native cowhage. The doses of capsaicin (A) and histamine (B) (200 and 10 mg/ml, respectively) were selected as the lowest concentrations required to produce sensations comparable in overall magnitude to those evoked by cowhage (C).

Fig. 6

Distributions of the categories on the gLMS scale chosen by 21 subjects to represent the sensations of itch, pricking/stinging and burning in response to capsaicin (200 mg/ml), histamine (10 mg/ml), and native cowhage (A, B, and C, respectively). Data presented are same as those used to calculate average responses in Fig. 5. The labels correspond to the following categories and numerical values on the gLMS scale: barely detectable (BD, ≤ 1), weak (WK, >1≤6), moderate (MD, >6≤17), strong (ST, >17≤35), very strong (VS, >35≤53) and greater than very strong (>VS, >53).

Fig. 7

The areas of dysesthesia evoked by a spicule containing native cowhage, capsaicin or histamine. A: Areas of each type of dysesthesia evoked in a subject given a single spicule of 100 mg/ml histamine. The mean areas of dysesthesia obtained in response to capsaicin (200 mg/ml), histamine (10 mg/ml) and native cowhage spicule are indicated for alloknesis (B), hyperknesis (C) and hyperalgesia (D).

Fig. 8

The areas of skin reactions evoked by histamine, capsaicin and cowhage. A: Skin reactions produced in a subject by capsaicin (200 mg/ml) and histamine (10 mg/ml) but not by cowhage. Areas of wheal (B) and flare (C) reported in individual subjects tested with a capsaicin (200 mg/ml), histamine (10 mg/ml) and cowhage. Cowhage and capsaicin never evoked a wheal. D–E: Mean areas of wheal and flare obtained in response to each type of spicule.