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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Ralvenius William T., Neumann Elena, Pagani Martina, Acuña Mario A., Wildner Hendrik, Benke Dietmar, Fischer Nina, Rostaher Ana, Schwager Simon, Detmar Michael, Frauenknecht Katrin, Aguzzi Adriano, Hubbs Jed Lee, Rudolph Uwe, Favrot Claude, Zeilhofer Hanns Ulrich,
Project Dorsal Horn Neuronal Circuits Processing Itch
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Original article (peer-reviewed)

Journal Nature Communications
Volume (Issue) 9(1)
Page(s) 3230 - 3230
Title of proceedings Nature Communications
DOI 10.1038/s41467-018-05709-0

Open Access

URL http://doi.org/10.1038/s41467-018-05709-0
Type of Open Access Publisher (Gold Open Access)

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.
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