NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury.
NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury.
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DOI：
10.1016/j.celrep.2018.04.107
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发表时间：
2018-05-29
期刊：
影响因子：
8.8
通讯作者：
Scholz J
中科院分区：
文献类型：
--
作者：
Inquimbert P;Moll M;Latremoliere A;Tong CK;Whang J;Sheehan GF;Smith BM;Korb E;Athié MCP;Babaniyi O;Ghasemlou N;Yanagawa Y;Allis CD;Hof PR;Scholz J
周围神经损伤引起脊髓背角细胞凋亡。细胞死亡的原因，神经元的参与，以及与躯体感觉信息处理的相关性是有争议的。在这里，我们证明了在小鼠坐骨神经损伤模型中，谷氨酸诱导的神经变性和浅表背角中γ-氨基丁酸（GABA）能中间神经元的丢失促进了从急性到慢性神经病理性疼痛的转变。Grin 1是N-甲基-D-天冬氨酸型谷氨酸受体（NMDARs）的重要亚基，条件性缺失Grin 1可保护背角神经元免受兴奋性毒性并保留GABA能抑制。功能性NMDAR缺陷的小鼠在神经损伤后表现出正常的伤害性反应和急性疼痛，但这种疼痛敏感性的初始增加是可逆的。消除NMDAR可以完全防止持续性疼痛样行为。缺乏促凋亡Bax的小鼠疼痛减轻证实了神经变性的重要性。我们的结论是NMDAR介导的神经元死亡有助于慢性神经病理性疼痛的发展。背角神经元处理躯体感觉信息，包括疼痛。Inquimbert等人利用空间限制性Grin 1基因敲除，表明NMDA受体介导的兴奋性输入导致神经损伤后一些背角神经元的变性。GABA能中间神经元的不可逆损失导致抑制缺陷，促进持续性疼痛超敏反应。
Peripheral nerve lesions provoke apoptosis in the dorsal horn of the spinal cord. The cause of cell death, the involvement of neurons, and the relevance for the processing of somatosensory information are controversial. Here, we demonstrate in a mouse model of sciatic nerve injury that glutamate-induced neurodegeneration and loss of γ-aminobutyric acid (GABA)ergic interneurons in the superficial dorsal horn promote the transition from acute to chronic neuropathic pain. Conditional deletion of Grin1, the essential subunit of N-methyl-D-aspartate-type glutamate receptors (NMDARs), protects dorsal horn neurons from excitotoxicity and preserves GABAergic inhibition. Mice deficient in functional NMDARs exhibit normal nociceptive responses and acute pain after nerve injury, but this initial increase in pain sensitivity is reversible. Eliminating NMDARs fully prevents persistent pain-like behavior. Reduced pain in mice lacking proapoptotic Bax confirmed the significance of neurodegeneration. We conclude that NMDAR-mediated neuron death contributes to the development of chronic neuropathic pain. Dorsal horn neurons process somatosensory information, including pain. Inquimbert et al. utilized spatially restricted Grin1 knockout to show that NMDA-receptor-mediated excitatory input causes the degeneration of some dorsal horn neurons after nerve injury. Irreversible loss of GABAergic interneurons leads to a deficit in inhibition that promotes persistent pain hypersensitivity.
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影响因子：
16.2
作者：
Cui, Lian;Miao, Xuerong;Liang, Lingli;Abdus-Saboor, Ishmail;Olson, William;Fleming, Michael S.;Ma, Minghong;Tao, Yuan-Xiang;Luo, Wenqin
通讯作者：
Luo, Wenqin
DOI：
10.1016/j.jpain.2009.09.008
发表时间：
2010-04
期刊：
The journal of pain
影响因子：
--
作者：
Corder G;Siegel A;Intondi AB;Zhang X;Zadina JE;Taylor BK
通讯作者：
Taylor BK
影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
7.3
作者：
Kahle KT;Schmouth JF;Lavastre V;Latremoliere A;Zhang J;Andrews N;Omura T;Laganière J;Rochefort D;Hince P;Castonguay G;Gaudet R;Mapplebeck JC;Sotocinal SG;Duan J;Ward C;Khanna AR;Mogil JS;Dion PA;Woolf CJ;Inquimbert P;Rouleau GA
通讯作者：
Rouleau GA
影响因子：
3.3
作者：
Lorenzo LE;Magnussen C;Bailey AL;St Louis M;De Koninck Y;Ribeiro-da-Silva A
通讯作者：
Ribeiro-da-Silva A