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.
Pubmed ID: 30104684 RIS Download
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Gene expression data and maps of mouse central nervous system. Gene expression atlas of developing adult central nervous system in mouse, using in situ hybridization and transgenic mouse techniques. Collection of pictorial gene expression maps of brain and spinal cord of mouse. Provides tools to catalog, map, and electrophysiologically record individual cells. Application of Cre recombinase technologies allows for cell-specific gene manipulation. Transgenic mice created by this project are available to scientific community.
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View all literature mentionsNational public repository system for mutant mice. Archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by biomedical research community. Includes breeding/distribution facilities and information coordinating center. Mice strains are cryopreserved, unless live colony must be established. Live mice are supplied from production colony, from colony recovered from cryopreservation, or via micro-injection of cell line into host blastocysts. MMRRC member facilities also develop technologies to improve handling of mutant mice, including advances in assisted reproductive techniques, cryobiology, genetic analysis, phenotyping and infectious disease diagnostics.
View all literature mentionsCenter that imports, archives, maintains, and distributes mutant mouse alleles as live mice, frozen germplasm, stem cells, and molecular vectors for use in biomedical research. The MMRRC Davis receives transgenics, knockouts, and other kinds of mutant mouse lines at no cost to the donor, and after re-derivation and cryopreservation, distributes breeding stock, germplasm, cells, or tissues of genetically-defined and pathogen-free mice for a small fee to requesting investigators.
View all literature mentionsMus musculus with name STOCK Tg(Grp-cre)KH288Gsat/Mmucd from MMRRC.
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