A Conditional Deletion of the NR1 Subunit of the NMDA Receptor in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain
A Conditional Deletion of the NR1 Subunit of the NMDA Receptor in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain
复制标题
DOI：
10.1523/jneurosci.23-12-05031.2003
复制
发表时间：
2003-06
期刊：
影响因子：
--
通讯作者：
S. South;T. Kohno;B. Kaspar;D. Hegarty;B. Vissel;C. Drake;M. Ohata;S. Jenab;A. Sailer;S. Malkmu
中科院分区：
文献类型：
--
作者：
S. South;T. Kohno;B. Kaspar;D. Hegarty;B. Vissel;C. Drake;M. Ohata;S. Jenab;A. Sailer;S. Malkmu
为了确定NMDA受体（NMDAR）在损伤后疼痛超敏反应中的重要性，通过向固定NR1小鼠局部注射表达Cre重组酶的腺相关病毒，选择性地缺失了成年小鼠腰椎脊髓中的NMDAR1 （NR1）亚基。NR1亚基mRNA和树突状蛋白在病毒注射区域减少80%，NMDA电流在II层神经元中减少86-88%，而AMPA电流没有减少。空间NR1敲除不会改变热或冷爪退缩潜伏期、机械阈值或运动功能。然而，足底福尔马林引起的损伤性疼痛减少了70%。我们的研究结果确凿地证明，脊髓腰背角的突触后NR1受体亚基是中枢致敏所必需的，中枢致敏是由外周损伤产生的疼痛传递的中枢促进。
To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86–88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury.