MiR‐200a‐3p Attenuates Neuropathic Pain by Suppressing the Bromodomain‐Containing Protein 3‐Nuclear Factor‐κB Pathway

Abstract

MicroRNAs (miRNAs) have key roles in the pathological processes of neuropathic pain. Here, our aim was to elucidate the function of miR‐200a‐3p as well as its related regulatory mechanism in neuropathic pain. An animal model of neuropathic pain was established by chronic constriction injury (CCI) induction. The knockdown experiments are performed by injecting a lentiviral construct intrathecally. MiR‐200a‐3p and bromodomain‐containing protein 3 (BRD3) expression in rat spinal cord was determined using RT‐qPCR. The mechanical, thermal, and cold responses in animals were assessed at the indicated time after surgery. The levels of inflammatory cytokines in rat spinal cord were measured by ELISA. The changes in NF‐κB signaling‐related molecules in rat spinal cord were determined using western blot and immunofluorescence. MiR‐200a‐3p was underexpressed in CCI rats in a time‐dependent manner. Overexpression of miR‐200a‐3p decreased mechanical hyperalgesia and thermal sensitivity to attenuate neuropathic pain in rats. BRD3 was targeted by miR‐200a‐3p. Additionally, downregulation of BRD3 inhibited neuropathic pain progression. Moreover, overexpression of BRD3 rescued the effect of miR‐200a‐3p on NF‐κB signaling and neuropathic pain in CCI rats. MiR‐200a‐3p attenuates neuropathic pain via downregulating BRD3 to block NF‐κB signaling.