上海交通大学学报(医学版)

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第三组代谢型谷氨酸受体亚型对神经病理性痛的影响

陈 锐,王 华,周全红,江 伟   

  1. 上海交通大学附属第六人民医院麻醉科, 上海 200233
  • 出版日期:2013-10-28 发布日期:2013-10-31
  • 通讯作者: 江 伟, 电子信箱: jiangw@sjtu.edu.cn。
  • 作者简介:陈 锐(1988—),女, 硕士生; 电子信箱: cryourfriend@163.com。
  • 基金资助:

    国家自然科学基金青年科学基金项目(81100825)

Effects of group Ⅲ metabotropic glutamate receptors subtypes on neuropathic pain

CHEN Rui, WANG Hua, ZHOU Quan-hong, JIANG Wei   

  1. Department of Anesthesiology, the Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China
  • Online:2013-10-28 Published:2013-10-31
  • Supported by:

    National Nature Science Foundation of China, 81100825

摘要:

目的 探讨第三组代谢型谷氨酸受体(mGluRs)亚型对神经病理性痛的调节作用。方法 取30只SD大鼠,随机分为5组(n=6),于鞘内置管术后第5天分别给予单次鞘内注射等容量(10 μL)生理盐水、L(+)-2-氨基-4-膦酰基丁酸(L-AP4)、VU0155041、AMN082和(S)-3,4-二甲酸苯基甘氨酸(DCPG),注药后每隔15 min和30 min分别测量大鼠50%机械缩足阈值(50%PWT)和缩足潜伏期(PWL)。另取30只SD大鼠,随机分为5组(n=6),鞘内置管并行脊神经根结扎(SNL),术后第7天给予单次鞘内注射生理盐水及同上药物10 μL,注药后同法测量大鼠50%PWT和PWL。再取18只SD大鼠,随机分为空白对照组、SNL组、SNL+注药组(生理盐水、VU0155041、AMN082和DCPG)(n=3),注药组于30 min后与其余各组同取腰膨大处脊髓,Western blotting检测mGluR4、mGluR7和mGluR8的表达。结果 L-AP4、VU0155041、AMN082和DCPG对正常大鼠的痛域无影响(P>0.05);但对神经病理性痛大鼠有不同程度的镇痛作用(P<0.05),其中以VU0155041效果最为显著。与空白对照组相比,SNL组手术同侧脊髓只有mGluR4表达水平降低(P<0.05);与生理盐水组相比,其他注药组只有mGluR4表达水平升高(P<0.05);而mGluR7在各组中的表达水平差异无统计学意义(P>0.05),mGluR8在脊髓基本不表达。结论 第三组mGluRs中主要是mGluR4对神经病理性痛有调节作用。

关键词: 第三组代谢型谷氨酸受体, 4型代谢型谷氨酸受体, 神经病理性痛

Abstract:

Objective To investigate the effects of group Ⅲ metabotropic glutamate receptors(mGluRs) subtypes on neuropathic pain. Methods Thirty SD rats were randomly divided into five groups (n=6), and received a single intrathecal injection of 10 μL saline, L-(+)-2-Amino-4-phosphonobutyric acid (L-AP4), VU0155041, AMN082 and (S)-3,4-Dicarboxyphenylglycine (DCPG) respectively on the fifth day after intrathecal catheterization. Values of 50% paw withdrawal threshold (50%PWT) and paw withdrawal latency (PWL) were measured every 15 min and 30 min after drugs administration respectively. Another thirty SD rats were randomly divided into five groups (n=6), and received a single intrathecal injection of 10 μL saline and ditto drugs respectively on the seventh day after spinal nerve ligation (SNL) surgery and intrathecal catheterization. Values of 50%PWT and PWL were measured as the ditto methods after drugs administration. Another eighteen SD rats were randomly divided into blank control group, SNL group and SNL+injection group(saline, VU0155041, AMN082 and DCPG)(n=3), all rats were taken the spinal cord at the lumbar enlargement 30 min after injection, and the expression of mGluR4, mGluR7 and mGluR8 was determined by Western blotting. Results L-AP4, VU0155041, AMN082 and DCPG had no influence on the normal rats (P>0.05), while had different analgesic effects on rats with neuropathic pain (P<0.05), in which VU0155041 had the most significant effect. The expression of mGluR4 in spinal cord in SNL group was significantly lower than that in blank control group (P<0.05), and the expression of mGluR4 in injection groups was significantly higher than that in saline group (P<0.05). There was no significant difference in the expression of mGluR7 among groups (P>0.05), and mGluR8 was hardly expressed in the spinal cord. Conclusion mGluR4 is the main subtype of group Ⅲ mGluRs involved in the regulation of neuropathic pain.

Key words: group Ⅲ metabotropic glutamate receptor, metabotropic glutamate receptor 4, neuropathic pain