Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats
Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats
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DOI：
10.1016/j.pain.2005.03.045
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发表时间：
2005-07-01
期刊：
影响因子：
7.4
通讯作者：
Chung, K
中科院分区：
文献类型：
--
作者：
Gao, X;Kim, HK;Chung, K
NR1 是功能性 NMDA 受体的重要组成部分，可通过磷酸化激活。这表明 NR1 (pNR1) 的磷酸化有助于皮内注射辣椒素后的中枢敏化。本研究调查脊髓 pNR1 的增加是否与中枢敏化相关，从而与神经性疼痛的疼痛行为相关。通过L5脊髓神经结扎产生神经病大鼠，测量爪的机械阈值，然后去除L4/5脊髓和股薄核(NG)并对pNR1进行免疫染色。结果显示，在神经结扎后第 3、7 和 28 天，同侧脊髓中 pNR1 免疫反应性神经元的数量显着增加，并且这些增加与机械性异常性疼痛相一致。仅在神经结扎后 28 天观察到 NG 中 pNR1 免疫反应性神经元的增加。 Western blot分析证实神经结扎后脊髓背角pNR1蛋白显着增加。蛋白激酶 A 抑制剂 H89 可适度逆转 7 天神经病大鼠的机械异常性疼痛。许多 pNR1 免疫反应性神经元被逆行示踪剂鉴定为投射神经元。数据表明PKA介导的NMDA受体磷酸化在脊神经结扎引起的神经性疼痛中发挥重要作用。 (C) 2005 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
NR1 is an essential component of functional NMDA receptors and can be activated by phosphorylation. It is suggested that phosphorylation of NR1 (pNR1) contributes to central sensitization after intradermal capsaicin injection. The present study investigates whether increases of spinal pNR1 are correlated to central sensitization and thus pain behaviors in neuropathic pain. Neuropathic rats were produced by L5 spinal nerve ligation, mechanical thresholds of the paw were measured, and then the L4/5 spinal cords and the nucleus gracilis (NG) were removed and immunostained for pNR1. The results showed that the number of pNR1-immunoreactive neurons was significantly increased in the ipsilateral cord, at 3, 7, and 28 days after nerve ligation and these increases coincide with mechanical allodynia. The increase of pNR1-immunoreactive neurons in the NG was observed only at 28 days after the nerve ligation. Western blot analyses confirmed the significant increase of pNR1 protein in spinal dorsal horn after nerve ligation. A protein kinase A inhibitor, H89, moderately reversed mechanical allodynia in 7 day neuropathic rats. Many pNR1-immunoreactive neurons were identified as projection neurons by retrograde tracer. The data suggest that PKA mediated NMDA receptor phosphorylation plays an important role in spinal nerve ligation induced neuropathic pain. (C) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.