Suppression of MALAT1 ameliorates chronic constriction injury-induced neuropathic pain in rats via modulating miR-206 and ZEB2.

Long noncoding RNAs (lncRNAs) are involved in multiple nervous system diseases, including neuropathic pain. Previous studies have demonstrated that lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a diagnostic biomarker in many diseases. Nevertheless, the function of MALAT1 in neuropathic pain progression is still unclear. Here, we established a chronic constriction injury (CCI) rat model. We found that MALAT1 was remarkably upregulated in CCI rats. In addition, neuropathic pain behaviors such as mechanical and thermal hyperalgesia were reduced by the inhibition of MALAT1. Meanwhile, the loss of MALAT1 was able to depress the neuroinflammation process via the inhibition of COX-2, interleukin-1β, and interleukin-6. A previous study has indicated that miR-206 upregulation can restrain the CCI-induced neuropathic pain. Furthermore, we exhibited that miR-206 was significantly downregulated and silence of MALAT1 restrained its expression in CCI rats. For another, ZEB2 was a target of miR-206 and it was shown that ZEB2 was elevated in CCI rats in a time-dependent manner. Overexpression of miR-206 obviously suppressed ZEB2 levels in rat microglial cells. Subsequently, it was demonstrated that upregulation of miR-206 rescued the neuropathic pain triggered by ZEB2 overexpression in vivo through neuroinflammation inhibition. Overall, we indicated that suppression of MALAT1 ameliorated neuropathic pain progression via miR-206/ZEB2 axis.