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
Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.
Neurochem Res. 2015 Mar;40(3):579-90. doi: 10.1007/s11064-014-1503-z. Epub 2014 Dec 30.
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.
胰岛细胞自身抗原69 kDa（ICA69）通过与蛋白激酶C相互作用蛋白1（PICK1）形成异源复合物，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的转运，对炎性疼痛超敏反应至关重要。然而，ICA69在炎性疼痛中的作用尚未得到研究。在此我们报道，在ICA69基因敲除小鼠中，脊髓中PICK1的表达大幅降低。在福尔马林给药7天后的第二阶段，疼痛超敏反应增强。同时，GluA2中Ser880磷酸化增加和表面GluA2减少与疼痛一致。此外，脊髓背角中活化小胶质细胞的数量随着疼痛超敏反应而增加。总之，ICA69缺乏促进了GluA2的内化和FML诱导的持久疼痛超敏反应。此外，小胶质细胞活化可能是疼痛超敏反应发生发展的一个重要因素。
