鞘内应用GIP受体拮抗剂抑制大鼠切口痛的敏化

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

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%氯化钠溶液溶液组(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。

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(PWT) to von Frey stimuli 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.