TY - JOUR

T1 - Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans

AU - Andersen, Hjalte H.

AU - Melholt, Camilla

AU - Hilborg, Sigurd D.

AU - Jerwiarz, Anne

AU - Randers, Amalie

AU - Simoni, Amalie

AU - Elberling, Jesper

AU - Arendt-Nielsen, Lars

PY - 2017/1/1

Y1 - 2017/1/1

N2 - A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/Lmenthol, respectively), on histamine-induced itch, wheals and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-test lancets. Recorded outcomeparameters were itch intensity, wheal reactions, and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical “cold-like” counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensitydependent manner (p < 0.05) and, to a lesser extent, also wheal reactions and neurogenic inflammation. Chemical “cold-like” counter-irritation with both Lmenthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p < 0.05). Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.

AB - A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/Lmenthol, respectively), on histamine-induced itch, wheals and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-test lancets. Recorded outcomeparameters were itch intensity, wheal reactions, and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical “cold-like” counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensitydependent manner (p < 0.05) and, to a lesser extent, also wheal reactions and neurogenic inflammation. Chemical “cold-like” counter-irritation with both Lmenthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p < 0.05). Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.

KW - Cold stimulation

KW - Counterirritation

KW - Histamine

KW - Itch

KW - TRPA1

KW - TRPM8

KW - TRPs

U2 - 10.2340/00015555-2447

DO - 10.2340/00015555-2447

M3 - Journal article

C2 - 27141849

AN - SCOPUS:85006997574

VL - 97

SP - 63

EP - 70

JO - Acta Dermato-Venereologica

JF - Acta Dermato-Venereologica

SN - 0001-5555

IS - 1

ER -