Deng Zeyu, Li Congcong, Du Errong, Liu Chenglong, Xia Bihan, Chen Huiyu, He Qiqing, Xu Changshui
Department of Physiology, Basic Medical College of Nanchang University, Nanchang, China.
The second clinical medical college of Nanchang University, Nanchang, China.
Cell Physiol Biochem. 2018;51(2):812-826. doi: 10.1159/000495334. Epub 2018 Nov 21.
BACKGROUND/AIMS: Neuropathic pain (NPP) is the consequence of a number of central nervous system injuries or diseases. Previous studies have shown that NPP is mediated by P2X4 receptors that are expressed on satellite glial cells (SGCs) of dorsal root ganglia (DRG). Catestatin (CST), a neuroendocrine multifunctional peptide, may be involved in the pathogenesis of NPP. Here, we studied the mechanism through which CST affects NPP.
We made rat models of chronic constriction injury (CCI) that simulate neuropathic pain. Rat behavioral changes were estimated by measuring the degree of hyperalgesia as assessed by the mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL). P2X4 mRNA expression was detected by quantitative real-time reverse transcription-polymerase chain reaction. P2X4 protein level and related signal pathways were assessed by western blot. Additionally, double-labeled immunofluorescence was employed to visualize the correspondence between the P2X4 receptor and glial fibrillary acidic protein. An enzyme-linked immunosorbent assay was performed to determine the concentration of CST and inflammatory factors.
CST led to lower MWT and TWL and increased P2X4 mRNA and protein expression on the SGCs of model rats. Further, CST upregulated the expression of phosphor-p38 and phosphor-ERK 1/2 on the SGCs of CCI rats. However, the expression level of phosphor-JNK and phosphor-p65 did not obviously change.
Taken together, CST might boost NPP by enhancing the sensitivity of P2X4 receptors in the DRG of rats, which would provide us a novel perspective and research direction to explore new therapeutic targets for NPP.
背景/目的：神经性疼痛（NPP）是多种中枢神经系统损伤或疾病的结果。先前的研究表明，NPP由背根神经节（DRG）卫星胶质细胞（SGC）上表达的P2X4受体介导。降钙素（CST）是一种神经内分泌多功能肽，可能参与NPP的发病机制。在此，我们研究了CST影响NPP的机制。
我们制作了模拟神经性疼痛的大鼠慢性压迫损伤（CCI）模型。通过测量机械缩足阈值（MWT）和热缩足潜伏期（TWL）评估的痛觉过敏程度来估计大鼠的行为变化。通过定量实时逆转录-聚合酶链反应检测P2X4 mRNA表达。通过蛋白质印迹法评估P2X4蛋白水平和相关信号通路。此外，采用双标免疫荧光法观察P2X4受体与胶质纤维酸性蛋白之间的对应关系。进行酶联免疫吸附测定以确定CST和炎症因子的浓度。
CST导致模型大鼠SGC上的MWT和TWL降低，P2X4 mRNA和蛋白表达增加。此外，CST上调了CCI大鼠SGC上磷酸化p38和磷酸化ERK 1/2的表达。然而，磷酸化JNK和磷酸化p65的表达水平没有明显变化。
综上所述，CST可能通过增强大鼠DRG中P2X4受体的敏感性来促进NPP，这将为我们探索NPP新治疗靶点提供新的视角和研究方向。
