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Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors

Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role of GRP in sensory neurons, we generated a floxed Grp mouse line. We found that conditional knockout of Grp...

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Detalles Bibliográficos
Autores principales: Barry, Devin M., Liu, Xue-Ting, Liu, Benlong, Liu, Xian-Yu, Gao, Fang, Zeng, Xiansi, Liu, Juan, Yang, Qianyi, Wilhelm, Steven, Yin, Jun, Tao, Ailin, Chen, Zhou-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070094/
https://www.ncbi.nlm.nih.gov/pubmed/32170060
http://dx.doi.org/10.1038/s41467-020-15230-y
Descripción
Sumario:Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role of GRP in sensory neurons, we generated a floxed Grp mouse line. We found that conditional knockout of Grp in sensory neurons results in attenuated non-histaminergic itch, without impairing histamine-induced itch. Using a Grp-Cre knock-in mouse line, we show that the upper epidermis of the skin is exclusively innervated by GRP fibers, whose activation via optogeneics and chemogenetics in the skin evokes itch- but not pain-related scratching or wiping behaviors. In contrast, intersectional genetic ablation of spinal Grp neurons does not affect itch nor pain transmission, demonstrating that spinal Grp neurons are dispensable for itch transmission. These data indicate that GRP is a neuropeptide in sensory neurons for non-histaminergic itch, and GRP sensory neurons are dedicated to itch transmission.