Effect of down-regulation of voltage-gated sodium channel Nav1.7 on activation of astrocytes and microglia in DRG in rats with cancer pain

ABSTRACT

Objective:To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain, and explore the transmission of the nociceptive information.Methods:Lentiviral vector harboring RNAi sequence targeting theNav1.7gene was constructed, and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats. Lentiviral vector was injected. Rats in each model were divided into 4 groups model group, PBS group, vehicle group and LV-Nav1.7 group. The expression levels of GFAP and OX42 in dorsal root ganglia (DRG) were measured.Results: After the animal model was built,the level of Nav1.7, GFAP and OX42 was improved obviously with the time prolonged, which was statistically significant (P<0.05). The expression level of GFAP and OX42 in the DRG in the LV-Nav1.7 group declined obviously compared to the model group, PBS group and vehicle group (P<0.05).Conclusions:Intrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7 and inhibit the activation of astrocytes and microglia in DRG. The effort is also effective in morphine tolerance bone cancer pain model rats.