Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Itch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors

Abstract

Chronic itch is a highly debilitating condition affecting about 10% of the general population. The relay of itch signals is under tight control by inhibitory circuits of the spinal dorsal horn, which may offer a hitherto unexploited therapeutic opportunity. Here, we found that specific pharmacological targeting of inhibitory α2 and α3GABAA receptors reduces acute histaminergic and non-histaminergic itch in mice. Systemic treatment with an α2/α3GABAA receptor selective modulator alleviates also chronic itch in a mouse model of atopic dermatitis and in dogs sensitized to house dust mites, without inducing sedation, motor dysfunction, or loss of antipruritic activity after prolonged treatment. Transsynaptic circuit tracing, immunofluorescence, and electrophysiological experiments identify spinal α2 and α3GABAA receptors as likely molecular targets underlying the antipruritic effect. Our results indicate that drugs targeting α2 and α3GABAA receptors are well-suited to alleviate itch, including non-histaminergic chronic itch for which currently no approved treatment exists.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Neuroscience Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
05 Vetsuisse Faculty > Veterinary Clinic > Department of Small Animals
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Physical Sciences > General Chemistry
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Physical Sciences > General Physics and Astronomy
Uncontrolled Keywords:General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry
Language:English
Date:13 August 2018
Deposited On:24 Aug 2018 17:09
Last Modified:18 May 2025 01:37
Publisher:Nature Publishing Group
ISSN:2041-1723
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41467-018-05709-0
PubMed ID:30104684
Project Information:
  • Funder: SNSF
  • Grant ID: 310030_156393
  • Project Title: Dorsal Horn Neuronal Circuits Processing Itch
Download PDF  'Itch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors'.
Preview
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
30 citations in Web of Science®
34 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

84 downloads since deposited on 24 Aug 2018
9 downloads since 12 months
Detailed statistics

Authors, Affiliations, Collaborations

Similar Publications