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

Devin M. Barry, Xue-Ting Liu, Benlong Liu, Xian-Yu Liu, Fang Gao, Xiansi Zeng, Juan Liu, Qianyi Yang, Steven Wilhelm, Jun Yin, Ailin Tao and Zhou-Feng Chen ()
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Devin M. Barry: Washington University School of Medicine
Xue-Ting Liu: Washington University School of Medicine
Benlong Liu: Washington University School of Medicine
Xian-Yu Liu: Washington University School of Medicine
Fang Gao: Washington University School of Medicine
Xiansi Zeng: Washington University School of Medicine
Juan Liu: Washington University School of Medicine
Qianyi Yang: Washington University School of Medicine
Steven Wilhelm: Washington University School of Medicine
Jun Yin: Washington University School of Medicine
Ailin Tao: Washington University School of Medicine
Zhou-Feng Chen: Washington University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15230-y

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