Downregulation of miR-206 contributes to neuropathic pain in rats by enhancing RASA1 expression

Neuropathic pain (NP), chronic pain resulted from dysfunction or diseases of the somatosensory nervous system, is a major challenge to currently available clinical therapy of peripheral nerve injury. Although there are significant improvements in drug and surgical therapy, the efficiency of the therapeutic approach for NP is low. And the molecular mechanisms of NP maintenance are still not clear. Herein, we investigated the novel role of miR-206 in regulating NP development in spinal nerve ligation (SNL) and chronic constriction injury (CCI) pain rats. RT-PCR analysis showed that the expression of miR-206 is aberrantly down-regulated in the dorsal root ganglion (DRG) of rats at days 7 and 14 after SNL or CCI compared to the control side. After transfection by miR-206 agomir, the paw withdrawal threshold to mechanical stimulus of SNL and CCI rats were alleviated by miR-206 overexpression, implying a role of miR-206 in NP. By bioinformatics and luciferase reporter analysis, RASA1 was proven to be a direct target of miR-206 with the binding site in 3’-UTR of mRNA. Further studies indicated that the protein level of RASA1 was increased in SNL and CCI rats, while miR-206 overexpression significantly down-regulated the expression of RASA1 protein. In contrast, the mRNA expression of RASA1 in DRG of SNL and CCI rats were unaffected by miR206 agomir. In conclusion, we demonstrated that miR-206 represents a potential suppressor in NP development through targeting RASA1. This may provide a novel understanding of miR-206 in negatively regulating peripheral sensitization to pain threshold and offer a potential therapeutic target in treating NP.