Nav1.8 induced ROS accumulation in keratinocyte by interacting with SOD2 directly. A, Nav.18 expression in NC and Nav1.8 knockdown keratinocyte treated with TNFα. B, IL-1β and IL-6 expression in NC and Nav1.8 knockdown keratinocyte treated with TNFα. C, P38, p-P38, P65, p-P65 expression in control and Nav1.8 knockdown keratinocyte treated with TNFα. D, IL-1β and IL-6 expression in control and A-803467-treated keratinocyte stimulated with TNFα. E, The ROS levels of keratinocyte treated with TNFα and Nav1.8 siRNA or A803467. F, The DHE straining of skin lesion from NC and Nav1.8 knockdown mice treated with IMQ or control or PBS or LL37. G, GO enrichment analysis of potential interaction proteins of Nav1.8 C-terminal. H, The ROS levels of and mRNA levels of IL-1β and IL-6 in Nav1.8-C overexpressed keratinocyte treated with mitoTEMPO. I, Co-IP revealed the interaction between Nav1.8-C and SOD2 in keratinocytes. J, The endogenous Co-IP revealed the interaction between Nav1.8 and SOD2 in DRG (Dorsal root ganglion). Data represents the mean ± SEM. and *p < 0.05, **p < 0.01, ***p < 0.001.2-way ANOVA test was used.