title: Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans.
abstract: 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/L-menthol, 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 outcome-parameters 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-intensity-dependent manner (p < 0.05) and, to a lesser extent, also wheal reactions and neurogenic inflammation. Chemical "cold-like" counter-irritation with both L-menthol 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.
authors.affiliation: Center for Sensory-Motor Interaction (SMI), Department of Health science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Hjalte H
authors.initials: HH
authors.lastname: Andersen
authors.forename: Camilla
authors.initials: C
authors.lastname: Melholt
authors.forename: Sigurd D
authors.initials: SD
authors.lastname: Hilborg
authors.forename: Anne
authors.initials: A
authors.lastname: Jerwiarz
authors.forename: Amalie
authors.initials: A
authors.lastname: Randers
authors.forename: Amalie
authors.initials: A
authors.lastname: Simoni
authors.forename: Jesper
authors.initials: J
authors.lastname: Elberling
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000982:Antipruritics / Q000494:pharmacology*; D003080:Cold Temperature; D004316:Doxepin / Q000494:pharmacology; D005260:Female; D064368:Healthy Volunteers; D006632:Histamine / Q000276:immunology*; D006633:Histamine Antagonists; D006801:Humans; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D011537:Pruritus / Q000276:immunology* / Q000517:prevention & control*; D016037:Single-Blind Method; D050051:Transient Receptor Potential Channels / Q000819:agonists*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000982:Antipruritics; D006633:Histamine Antagonists; D050051:Transient Receptor Potential Channels; D008610:Menthol; D004316:Doxepin; D000171:Acrolein; D006632:Histamine; C012843:cinnamaldehyde