基础医学与临床 ›› 2019, Vol. 39 ›› Issue (4): 467-472.

• 研究论文 • 上一篇    下一篇

鞘内应用GIP受体拮抗剂抑制大鼠切口痛的敏化

孙雨晴1,郭瑞娟2,李俊发3,王云1   

  1. 1. 首都医科大学附属北京朝阳医院
    2. 首都医科大学附属北京友谊医院
    3. 首都医科大学
  • 收稿日期:2018-12-20 修回日期:2019-01-15 出版日期:2019-04-05 发布日期:2019-03-26
  • 通讯作者: 王云 E-mail:wangyun129@ccmu.edu.cn
  • 基金资助:
    术后疼痛的新机制:脊髓背角GIP/GIP受体信号的作用;脊髓背角KA受体GluK2亚基功能调节及与AMPA受体GluR1亚基交叉谈话机制在术后疼痛中作用及干预研究

Intrathecal injection of glucose-dependent insulinotropic polypeptide receptors antagonist can inhibit the sensitization of incisional pain in rats

  • Received:2018-12-20 Revised:2019-01-15 Online:2019-04-05 Published:2019-03-26
  • Contact: Yun -Wang E-mail:wangyun129@ccmu.edu.cn

摘要: 目的 利用大鼠足底切口痛模型,探究葡萄糖依赖性促胰岛素分泌多肽(GIP)受体在疼痛中枢敏化中的作用。方法 将大鼠随机分为5组:空白对照组(Ctrl组)、假手术组(Sham组)、切口痛组(P组)、切口痛+鞘内注0.9%NaCl溶液组(I组)和切口痛+鞘内注GIP受体拮抗剂(Pro3)组(M组)。测定切口痛术前及术后3 h及1、3和5 d大鼠累计疼痛评分(CPS)和机械缩足阈值(PWT);Western blot检测GIP受体的表达;免疫荧光技术确定大鼠脊髓背角GIP受体的时空表达。结果 切口痛术后3 h时CPS评分最高(P<0.05),PWT最低(P<0.05);脊髓背角GIPR的表达水平在切口痛术后1 d显著上调(P<0.001);GIP受体拮抗剂(Pro3)可提高大鼠的机械缩足阈值,并在给药30 min时镇痛效果最佳(P<0.001);GIP受体位于脊髓背角浅层的神经元上,在小胶质细胞及星形胶质细胞上没有分布。结论 GIP受体参与了疼痛的中枢敏化,是切口痛的潜在治疗靶点。

关键词: 受体,GIP, 疼痛, 中枢敏化

Abstract: Objective To investigate the role of glucose-dependent insulinotropic polypeptide (GIP) receptors in central sensitization of pain with the plantar incision model of rats. Methods Rats were randomly divided into five groups: Control group (group Ctrl), sham operation group (group Sham), incisional pain group (group P), incisional pain + intrathecal normal saline group (group I), and incisional pain + intrathecal antagonist (Pro3)GIP group (group M). Cumulative pain score (CPS) and paw-withdrawal threshold to von Frey stimuli (PWT) were measured before incision and at 3 h and day 1, 3 and 5 after incision. The expression of GIPR in spinal cord dorsal horn was determined by Western blot analysis. The location of GIPR was examined by immunofluorescence staining. Results The CPS was significantly increased at 3 h after incision (P<0.05), the PWT was significantly decreased at the same time after incision (P<0.05). The expression of GIPR was up-regulated obviously 1 d after incision (P<0.001). Antagonist (Pro3)GIP increases the PWT of rats, and the best analgesic effects occurs at 30 minutes after intrathecal injection (P<0.001). Spinal GIPR was specifically expressed on neurons, and did not locate on astroglias or microglial cells. Conclusions GIPR plays a significant role in central sensitization of pain, and it provides a potential therapeutic target for incision pain.

Key words: Receptors, GIP, Pain, Central sensitization

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