气候变化领域集成服务门户(CCPortal): A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior

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DOI	10.1073/pnas.2021220118
	A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior
	Tashima R.; Koga K.; Yoshikawa Y.; Sekine M.; Watanabe M.; Tozaki-Saitoh H.; Furue H.; Yasaka T.; Tsuda M.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	A cardinal, intractable symptom of neuropathic pain is mechanical allodynia, pain caused by innocuous stimuli via low-threshold mechanoreceptors such as Aβ fibers. However, the mechanism by which Aβ fiber-derived signals are converted to pain remains incompletely understood. Here we identify a subset of inhibitory interneurons in the spinal dorsal horn (SDH) operated by adeno-associated viral vectors incorporating a neuropeptide Y promoter (AAV-NpyP+) and show that specific ablation or silencing of AAV-NpyP+ SDH interneurons converted touch-sensing Aβ fiber-derived signals to morphine-resistant pain-like behavioral responses. AAV-NpyP+ neurons received excitatory inputs from Aβ fibers and transmitted inhibitory GABA signals to lamina I neurons projecting to the brain. In a model of neuropathic pain developed by peripheral nerve injury, AAV-NpyP+ neurons exhibited deeper resting membrane potentials, and their excitation by Aβ fibers was impaired. Conversely, chemogenetic activation of AAV-NpyP+ neurons in nerve-injured rats reversed Aβ fiber-derived neuropathic pain-like behavior that was shown to be morphine-resistant and reduced pathological neuronal activation of superficial SDH including lamina I. These findings suggest that identified inhibitory SDH interneurons that act as a critical brake on conversion of touch-sensing Aβ fiber signals into pain-like behavioral responses. Thus, enhancing activity of these neurons may offer a novel strategy for treating neuropathic allodynia. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Inhibitory interneurons \| spinal dorsal horn \| primary afferent Aβ fibers \| mechanical allodynia \| neuropathic pain
语种	英语
scopus关键词	4 aminobutyric acid; amyloid beta protein; morphine; neuropeptide Y; Adeno associated virus; animal cell; animal experiment; animal model; Article; controlled study; disease course; drug resistance; excitatory junction potential; GABAergic transmission; interneuron; membrane steady potential; neuropathic pain; nonhuman; peripheral nerve injury; priority journal; rat; sensory gating; signal transduction; spinal cord dorsal horn
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180978
作者单位	Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan; Department of Neurophysiology, Hyogo College of Medicine, Nishinomiya, 663-8501, Japan; Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan; Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan; Department of Health and Nutrition, Faculty of Health Sciences, Niigata University of Health and Welfare, Niigata, 950-3198, Japan
推荐引用方式 GB/T 7714	Tashima R.,Koga K.,Yoshikawa Y.,et al. A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior[J],2021,118(3).
APA	Tashima R..,Koga K..,Yoshikawa Y..,Sekine M..,Watanabe M..,...&Tsuda M..(2021).A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Tashima R.,et al."A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).