Deletion of EGFL7 exacerbated chronic constriction-induced nerve damage and neuropathic pain by modulating the notch pathway 

Abstract

The pathogenesis of neuropathic pain (NP) is complex, and there is an urgent need to study its underlying mechanisms. A CCI rat model was established and injected with shRNA plasmid lentivirus to knock down EGFL7. Behavioral experiments were used to analyze pain thresholds in rats. Histologic hematoxylin-eosin (H&E) and toluidine blue staining were used to investigate the changes in tissue structure. Apoptosis was analyzed by TUNEL staining, while VWF was assessed by IHC for nerve repair evaluation. Finally, Western blot (WB) experiments were performed to analyze the potential molecular mechanisms underlying the regulation of EGFL7 in a rat model of CCI. The results showed that he absence of EGFL7 exacerbated pain in rats with CCI, resulting in disorganization of nerve cells in the sciatic nerve. It also caused extensive necrosis of the sciatic nerve and promoted demyelination and degeneration of axonal myelin. Large amounts of apoptosis were also present in the groups where EGFL7 was knocked down. In addition, the nerve repair factor VWF was also reduced in the CCI rat model with EGFL7 knockdown. Finally, mechanistic studies revealed that the knockdown of EGFL7 led to the downregulation of proteins related to the Notch signaling pathway. Our results suggested that inhibiting EGFL7 expression might worsen CCI-induced neuropathic pain and nerve injury in rats by affecting the Notch signaling pathway. This indicated that EGFL7 played a crucial role in the process of nerve injury. EGFL7 could also be a potential target for the treatment of neuropathic pain.