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学科主题: 基础医学
题名:
Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain
作者: Qu, Xiao-Xiu; Cai, Jie; Li, Ming-Jia; Chi, Ye-Nan; Liao, Fei-Fei; Liu, Feng-Yu; Wan, You; Han, Ji-Sheng; Xing, Guo-Gang1
关键词: NR2B-containing NMDA receptors ; Neuropathic pain ; Long-term potentiation ; Spinal dorsal horn ; WDR neurons ; Electrophysiology
刊名: EXPERIMENTAL NEUROLOGY
发表日期: 2009-02-01
DOI: 10.1016/j.expneurol.2008.10.018
卷: 215, 期:2, 页:298-307
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: LONG-TERM POTENTIATION ; METHYL-D-ASPARTATE ; FIBER-EVOKED POTENTIALS ; DORSAL-HORN NEURONS ; NR2B SUBUNIT ; RAT MODEL ; CENTRAL SENSITIZATION ; NERVE LIGATION ; MECHANICAL HYPERALGESIA ; SYNAPTIC-TRANSMISSION
英文摘要:

Activation of N-methyl-D-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for clinical pain therapy. (c) 2008 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 30370470 ; 2007CB512500
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号: WOS:000262890900012
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63089
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
2.Peking Univ, Dept Neurobiol, Beijing 100191, Peoples R China
3.Minist Educ, Key Lab Neurosci, Beijing 100191, Peoples R China
4.Minist Publ Hlth, Beijing 100191, Peoples R China

Recommended Citation:
Qu, Xiao-Xiu,Cai, Jie,Li, Ming-Jia,et al. Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain[J]. EXPERIMENTAL NEUROLOGY,2009,215(2):298-307.
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