Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans

• Published in: Neuroscience letters Vol. 666; pp. 186 - 189
• Main Authors: Andersen, Hjalte H., van Laarhoven, Antoinette I.M., Justesen, Frederik D., Pedersen, Jacob B., Sørensen, Laurits L., Jensen, Line P., Arendt-Nielsen, Lars
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 14.02.2018
• Subjects: Administration, Cutaneous; Adult; C-Fibers; Capsaicin; Capsaicin - pharmacology; Electric Stimulation - methods; Histamine; Histamine - pharmacology; Humans; Itch; Male; Nociceptors; Nociceptors - physiology; Pain Threshold - drug effects; Pruriceptors; Pruritus - chemically induced; Skin - physiopathology; TPRV1; Young Adult; C-Fibers; Histamine; Itch; Pruriceptors; TPRV1; Capsaicin; Nociceptors
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2017.11.061

•Capsaicin-sensitive fibers were ablated in humans validated by loss of warmth/heat pain sensitivity.•In ablated areas both electrically and histamine-evoked itch was profoundly inhibited.•It is proposed that electrically evoked itch is conveyed predominantly by TRPV1+ polymodal C-fibers. Specially designed transcutaneous electrical stimulation paradigms can be used to provoke experimental itch. However, it is unclear which primary afferent fibers are activated and whether they represent pathophysiologically relevant, C-fiber mediated itch. Since low-threshold mechano-receptors have recently been implicated in pruriception we aimed to characterize the peripheral primary afferent subpopulation conveying electrically evoked itch in humans (50Hz stimulation, 100μs square pulses, stimulus-response function to graded stimulus intensity). In 10 healthy male volunteers a placebo-controlled, 24-h 8% topical capsaicin-induced defunctionalization of capsaicin-sensitive (transient receptor potential V1-positive, ‘TRPV1’+) cutaneous fibers was performed. Histaminergic itch (1% solution introduced by a prick test lancet) was provoked as a positive control condition. Capsaicin pretreatment induced profound loss of warmth and heat pain sensitivity (pain threshold and supra-threshold ratings) as assessed by quantitative sensory testing, indicative of efficient TRPV1-fiber defunctionalization (all outcomes: P<0.0001). The topical capsaicin robustly, and with similar efficaciousness, inhibited itch intensity evoked by electrical stimulation and histamine (−89±4.1% and −78±4.9%, respectively, both: P<0.0001 compared to the placebo patch area). The predominant primary afferent substrate for electrically evoked itch in humans, using the presently applied stimulation paradigm, is concluded to be capsaicin-sensitive polymodal C-fibers.