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Sci Rep. 2017 Nov 13;7(1):15466. doi: 10.1038/s41598-017-15756-0.

Distinct roles of NMB and GRP in itch transmission.

Wan L1,2,3, Jin H1,2,4, Liu XY1,2, Jeffry J1,2, Barry DM1,2, Shen KF1,2,5, Peng JH1,2, Liu XT1,2,6, Jin JH1,2,7, Sun Y1,2,8, Kim R1, Meng QT1,2,9, Mo P1,2,10, Yin J1,2, Tao A6, Bardoni R11, Chen ZF12,13,14,15.

Author information

1
Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, 63110, USA.
2
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
3
Department of Pain Medicine, The State Key Clinical Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangdong, 510260, P.R. China.
4
Department of Anesthesiology, The First Hospital of Yunnan Province, Kunming, Yunnan, 650031, P.R. China.
5
Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China.
6
Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, P.R. China.
7
Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, P.R. China.
8
Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
9
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P.R. China.
10
Department of Anesthesiology, the Affiliated Nanhai Hospital of Southern Medical University, Foshan, Guangdong, 528000, P.R. China.
11
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, 41125, Italy.
12
Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, 63110, USA. chenz@wustl.edu.
13
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA. chenz@wustl.edu.
14
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA. chenz@wustl.edu.
15
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA. chenz@wustl.edu.

Abstract

A key question in our understanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter. Neuromedin B (NMB) is a mammalian member of the bombesin family of peptides closely related to GRP, but its role in itch is unclear. Here, we show that itch deficits in mice lacking NMB or GRP are non-redundant and Nmb/Grp double KO (DKO) mice displayed additive deficits. Furthermore, both Nmb/Grp and Nmbr/Grpr DKO mice responded normally to a wide array of noxious stimuli. Ablation of NMBR neurons partially attenuated peripherally induced itch without compromising nociceptive processing. Importantly, electrophysiological studies suggested that GRPR neurons receive glutamatergic input from NMBR neurons. Thus, we propose that NMB and GRP may transmit discrete itch information and NMBR neurons are an integral part of neural circuits for itch in the spinal cord.

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