Down-regulation of NOX4 expression in dorsal root ganglion of spinal cord could alleviate cancer induced bone pain in rats by reducing oxidative stress response

Abstract

Background Cancer-induced bone pain (CIBP) is a common complication in many patients with malignant tumors, and seriously affects their quality of life. Recent studies have implicated reactive oxygen species (ROS) in the perception and regulation of pain through the spinal cord, indicating their possible involvement in CIBP as well. NADPH oxidases (NOX) generate ROS such as H2O2, superoxide anion, nitric oxide etc. as byproducts of oxidative phosphorylation. In this study, we will analyze the expression levels of NOX4 and its mechanism of action in CIBP. Material and Methods A CIBP model was established in rats and NOX4 was knocked down in the dorsal root ganglia via intrathecal injection of specific lentivirus. The downstream effects of NOX4 knockdown were analyzed by RT-PCR, immunofluorescence and Western blotting. Results NOX4 was significantly upregulated in the rats with CIBP, and mainly localized in the microglia of the dorsal root ganglion of spinal cord. However, NOX4 knockdown alleviated CIBP by reducing oxidative stress and weakening spinal cord sensitization to pain. Conclusion Down-regulation of NOX4 in the dorsal root ganglion of spinal cord can alleviate CIBP by reducing oxidative stress.