Effects of ZXDC Mediates CCL2 on Chronic Neuropathic Pain in Spinal Dorsal Root Ganglion / 医学研究杂志

ABSTRACT

Objective To explore the effect and mechanism of C-C motif chemokine ligand 2(CCL2)/C-C chemokine receptor type 2(CCR2)signaling pathway mediated by ZXDC in spinal dorsal root ganglion(DRG)on neuropathic pain after chronic compressive injury.Methods A chronic compressive injury(CCI)mouse model was established.The expression of ZXDC and CCL2 in DRG was detected by immunofluorescence,Western blot,and real-time fluorescent quantitative PCR(RT-qPCR).The animals were divided in-to sham group,CCI+AAV-NC group,and CCI+AAV-ZXDC siRNA group.Western blot and immunofluorescence were employed to measure the expression of ZXDC,CCL2,and CCR2 in DRG after CCI,and the expression of pro-inflammatory factor TNF-α and IL-1β mRNA was evaluated by RT-qPCR.At last,the paw withdrawal threshold was used to evaluate the changes in neuropathic pain be-havior.Results ZXDC was localized in large,medium,and small DRG neurons.The expression of ZXDC and CCL2 protein and mRNA were significantly increased 1-3 days after CCI,and decreased 7days after CCI in DRG.The expression of ZXDC and CCL2mRNA was positively correlated(P＜0.05).3 days after CCI,compared with sham group,ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-NC group and CCI+AAV-ZXDC siRNA group were significantly increased,and ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-ZXDC siRNA group were significantly decreased than those in CCI+AAV-NC group(P＜0.05).Compared with sham group,the paw withdrawal threshold of CCI+AAV-ZXDC siRNA group and CCI+AAV-NC group were significantly decreased at various time points after CCI,and the withdrawal threshold in CCI+AAV-ZXDC siRNA group was significantly increased than that in CCI+AAV-NC group at 7days after CCI(P＜0.05).Conclusion Spinal dorsal root gan-glion ZXDC siRNA can inhibit neuropathic pain after CCI injury by downregulating CCL2/CCR2signaling axis.