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脊髓中 TRPV4 依赖的神经免疫轴促进神经病理性疼痛。

A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain.

机构信息

Department of Anesthesiology, Center for the Study of Itch and Sensory Disorders, and Washington University Pain Center and.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

出版信息

J Clin Invest. 2023 Mar 1;133(5):e161507. doi: 10.1172/JCI161507.

DOI:10.1172/JCI161507
PMID:36701202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9974096/
Abstract

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain.

摘要

小胶质细胞是中枢神经系统的固有巨噬细胞，对于大脑的发育、稳态和疾病都至关重要。小胶质细胞的激活和增殖是许多中枢神经系统疾病的标志，包括神经性疼痛。然而，在神经性疼痛的情况下，控制脊髓神经免疫轴的分子机制仍不完全清楚。在这里，我们发现瞬时受体电位香草酸亚型 4（TRPV4）的基因缺失或药理学阻断显著减弱了 spared nerve injury 小鼠模型中的神经性疼痛样行为。从机制上讲，小胶质细胞表达的 TRPV4 介导小胶质细胞的激活和增殖，并通过脂联素-2 的释放促进兴奋性脊髓神经元的功能和结构可塑性。我们的结果表明，小胶质细胞 TRPV4 通道位于脊髓神经免疫轴的中心，将外周神经损伤转化为中枢敏化和神经性疼痛，从而将 TRPV4 确定为治疗慢性疼痛的潜在新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/135cb24fcfed/jci-133-161507-g089.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/ac63ad818f45/jci-133-161507-g088.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/519c95cd5f7c/jci-133-161507-g090.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/cfbe0ce2d5e0/jci-133-161507-g091.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/e5ed4766609c/jci-133-161507-g092.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/08fa2e13f818/jci-133-161507-g093.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/46fe1d50f38e/jci-133-161507-g094.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/e380266fbee2/jci-133-161507-g095.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/8c28a5f66781/jci-133-161507-g096.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/98299b432cee/jci-133-161507-g097.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/135cb24fcfed/jci-133-161507-g089.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/ac63ad818f45/jci-133-161507-g088.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/519c95cd5f7c/jci-133-161507-g090.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/cfbe0ce2d5e0/jci-133-161507-g091.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/e5ed4766609c/jci-133-161507-g092.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/08fa2e13f818/jci-133-161507-g093.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/46fe1d50f38e/jci-133-161507-g094.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/e380266fbee2/jci-133-161507-g095.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/8c28a5f66781/jci-133-161507-g096.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/98299b432cee/jci-133-161507-g097.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fde/9974096/135cb24fcfed/jci-133-161507-g089.jpg

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A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain.

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[2]
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[6]
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[3]
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[4]
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[7]
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[8]
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[10]
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本文引用的文献

[1]
Thermosensitive TRPV4 channels mediate temperature-dependent microglia movement.

Proc Natl Acad Sci U S A. 2021-4-27

[2]
TRPV4 channels mediate the mechanoresponse in retinal microglia.

Glia. 2021-6

[3]
STING controls nociception via type I interferon signalling in sensory neurons.

Nature. 2021-3

[4]
TRP Channel Cooperation for Nociception: Therapeutic Opportunities.

Annu Rev Pharmacol Toxicol. 2021-1-6

[5]
Microglial calcium signaling is attuned to neuronal activity in awake mice.

Elife. 2020-7-27

[6]
The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises.

Pain. 2020-9-1

[7]
Spinal Wnt5a Plays a Key Role in Spinal Dendritic Spine Remodeling in Neuropathic and Inflammatory Pain Models and in the Proalgesic Effects of Peripheral Wnt3a.

J Neurosci. 2020-8-26

[8]
Sensitization of spinal itch transmission neurons in a mouse model of chronic itch requires an astrocytic factor.

J Allergy Clin Immunol. 2019-11-28

[9]
Nonnarcotic Methods of Pain Management.

N Engl J Med. 2019-6-20

[10]
A Comprehensive Algorithm for Management of Neuropathic Pain.

Pain Med. 2019-6-1

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