Mechanism Of Dexmedetomidine Enhancing Pain Threshold By Affecting SOCS3 Expression In Neuropathic Pain Mice

Objective: Neuropathic pain is a kind of pain characterized by mixed pain.Its pathogenesis is complex and its treatment is limited.So far,it is still a big difficulty faced by medical workers.The purpose of this study was to observe the effect of dexmedetomidine on the pain threshold of C57 mice with Chronic constriction injury of the sciatic nerve model after Intraperitoneal injection of dexmedetomidine,and analyze the expression of SOCS3 protein and released inflammatory factors to speculate the mechanism of dexmedetomidine in the treatment of neuropathic pain.Methods: Seventy-two male C57 mice weighing 18-25 grams and aged 6-8 weeks were randomly divided into three groups: Normal control(Sham)group,Chronic constriction injury of the sciatic nerve model(CCI)group and dexmedetomidine(DEX)group,Sham group only exposed sciatic nerve without any treatment,CCI group and DEX group after exposure of sciatic nerve ligation to establish sciatic compression injury mice model.After establishing sciatic nerve compression injury model,DEX group was intraperitoneally injected dexmedetomidine 50μg/kg/d for 5 consecutive days,CCI group was intraperitoneally injected with the same amount of normal saline.The incubation periods of heat and mechanical foot contraction were measured in mice of the three groups,and the spinal cord of mice L4-L6 was collected.The expression of TNF-α was determined by ENZY me-linked immunosorbent assay(ELISA),the localization and quantitative analysis of SOCS3 protein were analyzed by immunofluorescence staining,and the m RNA expression levels of SOCS3 and IL-6 were detected by reverse transcription polymerase chain reaction(RT-PCR).Results: After the successful establishment of the model,the thermal withdrawal latency and paw withdrawal mechanical threshold of C57 mice in each group were changed.By comparison,the postoperative thresholds of CCI group and DEX group were decreased compared with Sham group(P<0.05),while DEX group was increased compared with CCI group(P<0.05).Immunofluorescence staining and RT-PCR results showed that the expression of SOCS3 protein in DEX group was higher than that in CCI group(P<0.05),immunohistochemical staining showed that the activation degree of microglia was lower than that in CCI group,and the expression of inflammatory factors in DEX group was lower than that in CCI group(P<0.05).The expressions of IL-6 and TNF-α in L4-L6 spinal cord of mice were increased 3 days after operation(P<0.05),while SOCS3 was increased compared with CCI group on day 7(P<0.05),and lasted until day 10(P<0.05).Immunofluorescence results showed that the expression of SOCS3 around microglia in DEX group was higher than that in CCI group and Sham group on the 7th day after operation(P<0.05).Conclusion: The occurrence of neuropathic pain may be related to the activation and proliferation of microglia and release of inflammatory mediators.We speculated that dexmedetomidine increased the pain threshold of neuropathic pain C57 mice by promoting the expression of SOCS3 and inhibiting the activation of microglia and the release of inflammatory factors.Through this experiment,we further understand the mechanism of action,pharmacological characteristics and molecular mechanism of dexmedetomidine,which provides a new direction for the study of the mechanism of action in the treatment of neuropathic pain and the preparation of new relief drugs.