Tang Yuwen, Peng Zhiyou, Tao Shoujun, Sun Jianliang, Wang Wenyuan, Guo Xuejiao, Liu Gonglu, Luo Xianzhe, Chen Yuan, Shen Yue, Ma Haixiang, Xu Peng, Li Qinghua, Zhang Honghai, Feng Zhiying
Department of Anesthesiology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Pain Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Pain Res Manag. 2020 Feb 29;2020:4807674. doi: 10.1155/2020/4807674. eCollection 2020.
Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, it remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in inflammatory pain mediated by Cdk5 in the inflammatory pain model induced by complete Freund's adjuvant (CFA). Our results showed that the coexpression of Cdk5/VGLUT2 in small- and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.
已知囊泡谷氨酸转运体2（VGLUT2）在介导炎症诱导的热痛觉过敏中起重要作用。然而，这种作用的潜在机制尚不清楚。细胞周期蛋白依赖性激酶5（Cdk5）作为调节谷氨酸释放的关键调节因子，在炎性疼痛热痛觉过敏的形成中起关键作用。然而，Cdk5和VGLUT2之间是否存在介导炎性疼痛的桥梁仍不清楚。因此，我们设计了实验，以确定在完全弗氏佐剂（CFA）诱导的炎性疼痛模型中，VGLUT2信号通路是否参与Cdk5介导的炎性疼痛。我们的结果表明，在皮下注射CFA后第1至3天，背根神经节（DRG）和脊髓中小神经元细胞中Cdk5/VGLUT2的共表达显著增加。此外，我们的研究表明，在注射CFA后第1至3天，DRG和脊髓中VGLUT2蛋白的表达显著增加，并且被Cdk5的选择性拮抗剂roscovitine显著降低。另外，Cdk5的激活剂p25而非p35的蛋白表达被CFA显著增加，并被roscovitine降低。我们的研究结果表明，VGLUT2/Cdk5信号通路促成了Cdk5/p25介导的炎性疼痛。
