Inhibition of miR‐200b/miR‐429 contributes to neuropathic pain development through targeting zinc finger E box binding protein‐1

Many studies have reported that microRNAs participate in neuropathic pain development. Previously, miR‐200b and miR‐429 are reported to be involved in various diseases. In our current study, we focused on their roles in neuropathic pain and we found that miR‐200b and miR‐429 were significantly decreased in chronic constriction injury (CCI) rat spinal cords and isolated microglials. miR‐200b and miR‐429 overexpression were able to relieve neuropathic pain through modulating PWT and PWL in CCI rats. Meanwhile, we observed that both miR‐200b and miR‐429 upregulation could repress neuroinflammation via inhibiting inflammatory cytokines such as IL‐6, IL‐1β, and TNF‐α in CCI rats. By carry out bioinformatics technology, Zinc finger E box binding protein‐1 (ZEB1) was predicted as target of miR‐200b, and miR‐429 and dual‐luciferase reporter assays confirmed the correlation between them. ZEB1 has been reported to regulate a lot of diseases. Here, we found that ZEB1 was greatly increased in CCI rats and miR‐200b and miR‐429 overexpression markedly suppressed ZEB1 mRNA expression in rat microglial cells. In addition, knockdown of ZEB1 can reduce neuropathic pain development and co‐transfection of LV‐anti‐miR‐200b/miR‐429 reversed this phenomenon in vivo. Taken these together, our results suggested that miR‐200b/miR‐429 can serve as an important regulator of neuropathic pain development by targeting ZEB1. A biological role of miR‐200b/miR‐429 in neuropathic pain progression was focused on in our present research. We observed that LV‐miR‐200b/miR‐429 alleviated neuropathic pain development by downregulating ZEB1, and LV‐shZEB1 can inhibit neuropathic pain development, which can be reversed by LV‐anti‐ miR‐200b/miR‐429 in vitro. Our data revealed that miR‐200b/miR‐429 may function as an effective therapeutic target for treating neuropathic pain.