Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-D-aspartate receptor in spinal cord dorsal horn
Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-D-aspartate receptor in spinal cord dorsal horn
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DOI：
10.1016/j.neuroscience.2008.06.024
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发表时间：
2008-08-26
期刊：
影响因子：
3.3
通讯作者：
Inturrisi, C. E.
中科院分区：
文献类型：
--
作者：
Cheng, H. T.;Suzuki, M.;Inturrisi, C. E.
脊髓背角（SCDH）的N-甲基-D-天冬氨酸（NMDA）受体是参与慢性疼痛中枢敏感化的机制之一。此前，该实验室在小鼠SCDH中创建了N-甲基-D-天冬氨酸受体I（NR 1）亚基的时空敲除（KO）。NR 1 KO完全阻断NR 1基因和随后的NMDA受体在SCDH神经元中的表达和功能。在NR 1 KO小鼠中，完全弗氏佐剂（CFA）后24 h诱导的机械和冷异常性疼痛减少。然而，KO的保护作用是短暂的，并且在CFA后48小时未观察到。这些观察结果表明，存在非NMDA依赖性途径，有助于CFA诱导的疼痛。CFA诱导SCDH中几个信号级联的激活，包括蛋白激酶C（PKC）γ和细胞外信号调节激酶（ERK 1/2）。CFA处理后48 h，NR 1 KO小鼠SCDH中PKC γ和ERK 1/2的磷酸化受到抑制，表明这些途径是NMDA受体依赖性的。有趣的是，CFA后48 h，NR 1 KO的SCDH中诱导了神经元环氧合酶（考克斯）-2表达和小胶质细胞p38磷酸化。我们的研究结果提供的证据表明，炎症反应是负责疼痛复发后NR 1 KO在SCDH。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The N-methyl-D-aspartate (NMDA) receptor in the spinal cord dorsal horn (SCDH) is one of the mechanisms involved in central sensitization during chronic pain. Previously, this laboratory created a spatio-temporal knockout (KO) of the N-methyl-D-aspartate receptor I (NR1) subunit in the mouse SCDH. The NR1 KO completely blocks NR1 gene and subsequent NMDA receptor expression and function in SCDH neurons. In the NR1 KO mice, the mechanical and cold allodynia induced at 24 h after complete Freund's adjuvant (CFA) was reduced. However, the protective effects of KO were transient and were not seen at 48 h after CFA. These observations suggest the presence of NMDA-independent pathways that contribute to CFA-induced pain. CFA induces the activation of several signaling cascades in the SCDH, including protein kinase C (PKC)gamma and extracellular signal-regulated kinases (ERK1/2). The phosphorylation of PKC gamma and ERK1/2 was inhibited in the SCDH of NR1 KO mice up to 48 h after CFA treatment, suggesting that these pathways are NMDA receptor-dependent. Interestingly, neuronal cyclooxygenase (COX) -2 expression and microglial p38 phosphorylation were induced in the SCDH of the NR1 KO at 48 h after CFA. Our findings provide evidence that inflammatory reactions are responsible for the recurrence of pain after NR1 KO in the SCDH. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.