Spinal<i> Nmur2</i>-positive Neurons Play a Crucial Role in Mechanical Itch

doi:10.1016/j.jpain.2024.02.018

	Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch
	Xu, Jun-Feng 1; Liu, Lian 2; Liu, Yuan1,3,4,5 ; Lu, Ke-Xing 1; Zhang, Jun ; Zhu, Yan-Jing 1; Fang, Fang 2; Dou, Yan-Nong 1
	2024-08-01
发表期刊	JOURNAL OF PAIN (IF:4.0[JCR-2023],5.0[5-Year])
ISSN	1526-5900
EISSN	1528-8447
卷号	25 期号:8
发表状态	已发表
DOI	10.1016/j.jpain.2024.02.018
摘要	The dorsal spinal cord is crucial for the transmission and modulation of multiple somatosensory modalities, such as itch, pain, and touch. Despite being essential for the well-being and survival of an individual, itch and pain, in their chronic forms, have increasingly been recognized as clinical problems. Although considerable progress has been made in our understanding of the neurochemical processing of nociceptive and chemical itch sensations, the neural substrate that is crucial for mechanical itch processing is still unclear. Here, using genetic and functional manipulation, we identified a population of spinal neurons expressing neuromedin U receptor 2 ( Nmur2 + ) as critical elements for mechanical itch. We found that spinal Nmur2+ + neurons are predominantly excitatory neurons, and are enriched in the superficial laminae of the dorsal horn. Pharmacogenetic activation of cervical spinal Nmur2+ + neurons evoked scratching behavior. Conversely, the ablation of these neurons using a caspase-3-based method decreased von Frey filament-induced scratching behavior without affecting responses to other somatosensory modalities. Similarly, suppressing the excitability of cervical spinal Nmur2+ + neurons via the overexpression of functional Kir2.1 potassium channels reduced scratching in response to innocuous mechanical stimuli, but not to pruritogen application. At the lumbar level, pharmacogenetic activation of these neurons evoked licking and lifting behaviors. However, ablating these neurons did not affect the behavior associated with acute pain. Thus, these results revealed the crucial role of spinal Nmur2+ + neurons in mechanical itch. Our study provides important insights into the neural basis of mechanical itch, paving the way for developing novel therapies for chronic itch. Perspective: Excitatory Nmur2+ + neurons in the superficial dorsal spinal cord are essential for mechanical but not chemical itch information processing. These spinal Nmur2+ + neurons represent a potential cellular target for future therapeutic interventions against chronic itch. Spinal and supraspinal Nmur2+ + neurons may play different roles in pain signal processing. (c) 2024 (c) Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc All rights reserved.
关键词	Nmur2-positive neurons spinal cord mechanical itch somatosensation nociception
URL	查看原文
收录类别	SCI
语种	英语
WOS研究方向	Neurosciences & Neurology
WOS类目	Clinical Neurology ; Neurosciences
WOS记录号	WOS:001283763300001
出版者	CHURCHILL LIVINGSTONE
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/414167
专题	生命科学与技术学院生命科学与技术学院_博士生
通讯作者	Dou, Yan-Nong
作者单位	1.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Neurosci, Inst Neurosci, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Endocrinol & Metab Dis, Shanghai, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 4.Lingang Lab, Shanghai, Peoples R China 5.Army Med Univ, Daping Hosp, Dept Anesthesiol, Chongqing, Peoples R China
推荐引用方式 GB/T 7714	Xu, Jun-Feng,Liu, Lian,Liu, Yuan,et al. Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch[J]. JOURNAL OF PAIN,2024,25(8).
APA	Xu, Jun-Feng.,Liu, Lian.,Liu, Yuan.,Lu, Ke-Xing.,Zhang, Jun.,...&Dou, Yan-Nong.(2024).Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch.JOURNAL OF PAIN,25(8).
MLA	Xu, Jun-Feng,et al."Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch".JOURNAL OF PAIN 25.8(2024).