Characterization of N-methyl-D-aspartate receptor subunits responsible for postoperative pain
Characterization of N-methyl-D-aspartate receptor subunits responsible for postoperative pain
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DOI：
10.1016/j.ejphar.2004.09.033
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发表时间：
2004-10-25
影响因子：
5
通讯作者：
Ito, S
中科院分区：
文献类型：
--
作者：
Nishimura, W;Muratani, T;Ito, S
N-甲基-D-天冬氨酸（NMDA）受体已被认为是中枢致敏的发展，这可能会扩大术后疼痛的关键。NMDA受体由GluRxi（NR 1）与四个GluReptid 1-4（NR 2A-D）亚基中的任一个形成。为了阐明NMDA受体在术后疼痛中的作用，我们研究了GluRepsilon 2选择性拮抗剂（1 S，2S）-1-（4-羟基苯基）-2-（4-羟基-4-苯基哌啶基）-1-丙醇（CP-101，606）对足底切口引起的术后疼痛的影响。我们还将术后疼痛模型应用于GluRe 1和GluRepsilon 4基因敲除小鼠。切开前30分钟鞘内注射CP-101，606可显著增加术后2小时和1-3天的机械性退缩阈值，并剂量依赖性地减少术后疼痛。GuRepsilon 1和GluRepsilon 4基因敲除小鼠与野生型小鼠相比，在退缩阈值方面均未显示出差异。用CP-101，606预处理未在小鼠中产生附加的镇痛作用。这些结果表明，含GluRepsilon 2的NMDA受体参与术后疼痛，CP-101，606可能有效减轻疼痛。（C）2004 Elsevier B. V.保留所有权利。
N-methyl-D-aspartate (NMDA) receptors have been suggested to be critical for the development of central sensitization, which may amplify postoperative pain. NMDA receptors are formed by GluRxi (NR1) with any one of four GluRepsilon 1-4 (NR2A-D) subunits. To clarify the involvement of NMDA receptors in postoperative pain, we examined the effect of the GluRepsilon2-selective antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenyl piperidino)-1-propanol (CP-101,606) on postoperative pain caused by plantar incision. We also applied the postoperative pain model to GluRe1 and GluRepsilon4 knockout mice. CP-101,606 administered intrathecally 30 min prior to incision significantly increased mechanical withdrawal thresholds 2 h and 1-3 days after surgery and reduced postoperative pain dose-dependently. Neither GuRepsilon1 nor GluRepsilon4 knockout mice showed a difference in withdrawal thresholds as compared with wild-type mice. Pretreatment with CP-101,606 did not produce an additive analgesic effect in the mice. These results demonstrate that GluRepsilon2-containing NMDA receptors are involved in postoperative pain and that CP-101,606 may be effective in reducing it. (C) 2004 Elsevier B.V. All rights reserved.