Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity
Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity
复制标题
鞘内注射 GRIP-siRNA 减少大鼠背角红藻氨酸受体 GluK2 亚基的术后突触丰度和疼痛超敏反应
DOI：
10.1007/s11064-021-03323-z
复制
发表时间：
2021-04-13
影响因子：
4.4
通讯作者：
Wang，Yun
中科院分区：
文献类型：
--
作者：
Guo，Ruijuan;Li，Huili;Wang，Yun
术后疼痛的机制不同于炎症性或神经性疼痛。以往的研究表明，鞘内注射α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）-红藻氨酸（KA）受体拮抗剂可抑制痛觉防卫行为和机械性痛觉过敏，提示脊髓KA受体在术后痛觉过敏中起重要作用。然而，脊髓KA受体亚单位的功能调节如何参与术后疼痛超敏反应仍然是一个谜。因此，在本研究中，我们研究了脊髓KA受体亚单位的突触传递和KA受体亚单位和谷氨酸受体相互作用蛋白（GRIP）之间的相互作用在术后疼痛。我们的数据表明，足底切口诱导突触传递的GluK 2，但不GluK 1或GluK 3在同侧脊髓后角。免疫共沉淀结果显示，切伤后6 h，同侧脊髓背角神经元GluK 2-GRIP相互作用增强。有趣的是，鞘内预处理GRIP siRNA增加了机械刺激的缩爪阈值，并降低了切口后6小时切口同侧爪的累积疼痛评分。此外，鞘内预处理GRIP siRNA减少了足底切口后6 h同侧脊髓背角中GluK 2的突触丰度。总之，我们的数据表明，背角神经元中GluK 2- GRIP相互作用介导的突触丰度在术后疼痛超敏反应中起着重要作用。破坏GluK 2- GRIP相互作用可能为缓解术后疼痛提供一种新的方法。
The mechanisms underlying postoperative pain differ from the inflammatory or neuropathic pain. Previous studies have demonstrated that intrathecal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) -kainate (KA) receptor antagonist inhibits the guarding pain behavior and mechanical hyperalgesia, indicating a critical role of spinal KA receptors in postoperative pain hypersensitivity. However, how the functional regulations of spinal KA receptor subunits are involved in the postoperative pain hypersensitivity remains elusive. Therefore, in the current study, we investigated the synaptic delivery of spinal KA receptor subunits and the interaction between KA receptor subunits and glutamate receptor-interacting protein (GRIP) during the postoperative pain. Our data indicated that plantar incision induced the synaptic delivery of GluK2, but not GluK1 or GluK3 in ipsilateral spinal cord dorsal horns. The co-immunoprecipitation showed an increased GluK2 –GRIP interaction in ipsilateral dorsal horn neurons at 6 h post-incision. Interestingly, Intrathecal pretreatment of GRIP siRNA increased the paw withdrawal thresholds to mechanical stimuli and decreased the cumulative pain scores in the paws ipsilateral to the incision at 6 h post-incision. Additionally, Intrathecal pretreatment of GRIP siRNA reduced the synaptic abundance of GluK2 in ipsilateral spinal dorsal horn at 6 h after plantar incision. In general, our data have demonstrated that the GluK2- GRIP interaction-mediated synaptic abundance of GluK2 in dorsal horn neurons plays an important role in the postoperative pain hypersensitivity. Disrupting the GluK2- GRIP interaction may provide a new approach for relieving postoperative pain.