TY - JOUR
T1 - Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors
AU - Barry, Devin M.
AU - Liu, Xue Ting
AU - Liu, Benlong
AU - Liu, Xian Yu
AU - Gao, Fang
AU - Zeng, Xiansi
AU - Liu, Juan
AU - Yang, Qianyi
AU - Wilhelm, Steven
AU - Yin, Jun
AU - Tao, Ailin
AU - Chen, Zhou Feng
N1 - Funding Information:
We thank P. Yeager and G. Thompson for technical support and lab members for comments. We also thank M. Goulding and Q. Ma for generously providing Lbx1Flpo and Tauds-DTR lines, and X. Dong for kindly helping with generation of floxed GRP mice at Johns Hopkins University School of Medicine Department of Neuroscience Murine Mutagenesis Core. The project has been supported by the NIH grants 1R01AR056318-06, R01NS094344, R01 DA037261-01A1, and R56 AR064294-01A1 (Z.F.C) and the National Science and Technology Major Project of China (2016ZX08011-005) (A.T.).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081986004&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-15230-y
DO - 10.1038/s41467-020-15230-y
M3 - Article
C2 - 32170060
AN - SCOPUS:85081986004
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1397
ER -