It is unclear whether glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling plays an important role in spinal nociception. We hypothesized that the spinal GIPR is implicated in central sensitization of postoperative pain. Our data showed that the cumulative pain scores peaked at 3 h, kept at a high level at 1 d after incision, gradually decreased afterwards and returned to the baseline values at 5 d after incision. Correspondingly, the expression of GIPR in spinal cord dorsal horn peaked at 1 d after incision, and returned to the baseline value at 5 d after incision. The double-labeling immunofluorescence demonstrated that spinal GIPR was expressed in dorsal horn neurons, but not in astrocyte or microglial cells. At 1 d after incision, the effects of intrathecal saline, GIPR antagonist (Pro3)GIP on pain behaviors were investigated. Our data showed that at 30 min and 60 min following intrathecal treatments of 300 ng (Pro3)GIP, the cumulative pain scores were decreased and paw withdrawal thresholds to mechanical stimuli were increased when compared to those immediately before intrathecal treatments. Accordingly, at 30 min after intrathecal injections, the membrane translocation levels of PKCγ and the GluR1 expression in postsynaptic membrane in ipsilateral dorsal horns to the incision were significantly upregulated in rats with intrathecal saline injections, as compared to normal control group. At 30 min after intrathecal treatment, (Pro3)GIP inhibited the membrane translocation levels of PKCγ and the GluR1 expression in postsynaptic membrane in ipsilateral dorsal horns. Our study indicates that upregulation of spinal GIPR may contribute to pain hypersensitivity through inducing membrane translocation level of PKCγ and synaptic target of AMPA receptor GluR1 subunits in ipsilateral dorsal horns of rats with plantar incision.

中文翻译：

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脊髓葡萄糖依赖性促胰岛素多肽受体的上调诱导了大鼠切入痛模型中背角的PKCγ膜移位和AMPA受体GluR1亚基的突触靶标。

尚不清楚葡萄糖依赖性促胰岛素多肽受体（GIPR）信号在脊髓伤害感受中是否起重要作用。我们假设脊柱GIPR与术后疼痛的中枢敏化有关。我们的数据显示，累积的疼痛评分在切口3 h达到峰值，在切口1 d处保持较高水平，之后逐渐降低，并在切口5 d后恢复到基线值。相应地，GIPR在脊髓背角的表达在切开后1 d达到高峰，并在切开后5 d恢复到基线值。双重标记的免疫荧光显示脊髓GIPR在背角神经元中表达，但在星形胶质细胞或小胶质细胞中不表达。切口后1 d，研究鞘内注射生理盐水，GIPR拮抗剂（Pro3）GIP对疼痛行为的影响。我们的数据显示，与鞘内治疗前相比，鞘内注射300 ng（Pro3）GIP后30分钟和60分钟时，累积疼痛评分降低，爪对机械刺激的退缩阈值增加。因此，与鞘内注射生理盐水相比，鞘内注射大鼠在鞘内注射后30分钟，同侧背角至切口的突触后膜中PKCγ的膜移位水平和突触后膜中的GluR1表达显着上调。鞘内治疗后30分钟，（Pro3）GIP抑制同侧背角突触后膜中PKCγ的膜移位水平和GluR1表达。