Loss of ICA69 Potentiates Long-Lasting Hyperalgesia After Subcutaneous Formalin Injection into the Mouse Hindpaw
Loss of ICA69 Potentiates Long-Lasting Hyperalgesia After Subcutaneous Formalin Injection into the Mouse Hindpaw
复制标题
小鼠后爪皮下注射福尔马林后，ICA69 缺失会增强持久的痛觉过敏
DOI：
10.1007/s11064-014-1503-z
复制
发表时间：
2015
影响因子：
4.4
通讯作者：
Wang Jun-Lu
中科院分区：
文献类型：
--
作者：
Li Qian-Jun;Wang Zhen;Yao Yong-Xing;Jin Shen-Hui;Qian Mei-Zi;Li Na-Na;Wang Ya-Nan;Zhang Ya-Wen;Chen Bin-Yu;Jia Dan-Yun;Shen Ying;Wang Jun-Lu
胰岛细胞自身抗原 69 kDa (ICA69) 通过与 C 激酶 1 (PICK1) 相互作用的蛋白质形成异聚复合物，在许多疾病和生理活动中发挥重要作用。 PICK1 通过调节脊髓神经元中 AMPA 受体亚基 GluA2 的运输，对于炎性疼痛过敏至关重要。然而，ICA69 在炎性疼痛中的作用尚未得到研究。在这里，我们报道了 ICA69 敲除小鼠脊髓中 PICK1 的表达大幅降低。施用福尔马林后 7 天，第二阶段的疼痛过敏性增强。同时，GluA2 中 Ser880 磷酸化的增加和表面 GluA2 的减少与疼痛一致。此外，脊髓背角中活化的小胶质细胞数量随着疼痛超敏反应的增加而增加。 ICA69 缺陷共同促进了 GluA2 的内化和 FML 诱导的持久疼痛超敏反应。此外，小胶质细胞激活可能是疼痛超敏反应发生的重要因素。
Islet-cell autoantigen 69 kDa (ICA69) plays an important role in many diseases and physiological activities by forming heteromeric complexes with protein interacts with C-kinase 1 (PICK1). PICK1 is critical for inflammatory pain hypersensitivity by regulating trafficking of AMPA receptor subunit GluA2 in spinal neurons. However, the role of ICA69 in inflammatory pain has not yet been investigated. Here we reported that expression of PICK1 in spinal cord was reduced largely in ICA69 knockout mice. The pain hypersensitivity was enhanced in the second phase 7 days after formalin administration. Meanwhile, increased Ser880 phosphorylation in GluA2 and decreased surface GluA2 were concordant with the pain. Furthermore, the number of activated microglia in spinal dorsal horn increased in line with pain hypersensitivity. Together, ICA69 deficiency promoted the internalization of GluA2 and FML-induced long-lasting pain hypersensitivity. In addition, microglia activation might be an important factor in the development of the pain hypersensitivity.