Open AccessP-Rex2 mediation of synaptic plasticity contributes to bone cancer pain
Author(s) -
Qiaochu Fu,
Xiaoxia Huang,
WenCui Li,
Shengjun Wan,
Li Yang,
Xiaohui Li,
Shanchun Su,
Xueqin Xu,
Yiling Wu
Publication year - 2022
Publication title -
molecular pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.081
H-Index - 83
ISSN - 1744-8069
DOI - 10.1177/17448069221076460
Subject(s) - ampa receptor , gene knockdown , dendritic spine , rac1 , synaptic plasticity , glutamate receptor , microbiology and biotechnology , medicine , guanine nucleotide exchange factor , neuroscience , chemistry , biology , receptor , signal transduction , hippocampal formation , biochemistry , apoptosis
Bone cancer pain (BCP) seriously affects the quality of life; however, due to its complex mechanism, the clinical treatment was unsatisfactory. Recent studies have showed several Rac-specific guanine nucleotide exchange factors (GEFs) that affect development and structure of neuronal processes play a vital role in the regulation of chronic pain. P-Rex2 is one of GEFs that regulate spine density, and the present study was performed to examine the effect of P-Rex2 on the development of BCP. Tumor cells implantation induced the mechanical hyperalgesia, which was accompanied by an increase in spinal protein P-Rex2, phosphorylated Rac1 (p-Rac1) and phosphorylated GluR1 (p-GluR1), and number of spines. Intrathecal injection a P-Rex2-targeting RNAi lentivirus relieved BCP and reduced the expression of P-Rex2, p-Rac1, p-GluR1, and number of spines in the BCP mice. Meanwhile, P-Rex2 knockdown reversed BCP-enhanced AMPA receptor (AMPAR)-induced current in dorsal horn neurons. In summary, this study suggested that P-Rex2 regulated GluR1-containing AMPAR trafficking and spine morphology via Rac1/pGluR1 pathway is a fundamental pathogenesis of BCP. Our findings provide a better understanding of the function of P-Rex2 as a possible therapeutic target for relieving BCP.