甲基乙二醛在糖尿病神经病理性痛中的致敏作用OA

Objective To investigate the role of hyperglycemic metabolite methylglyoxal(MG)in the pathogenesis of diabetic neuro-pathic pain(DNP)and its relationship with spinal central sensitization.Methods Twenty-four C57BL/6 mice were randomly divided into DNP model group(single intraperitoneal injection of streptozotocin)and DNP control group(intraperitoneal injection of equal volume sodium citrate buffer),with 12 mice in each group.The remaining 12 mice were randomly divided into MG group(single intra-peritoneal injection of MG)and MG control group(intraperitoneal injection of equal volume saline),with 6 mice in each group.Mechanical paw withdrawal threshold(PWT)and thermal paw withdrawal latency(PWL)were assessed using the von Frey and the Hargreaves test,respectively.Measurements were performed at weeks 1,2,4 after modeling and at 30,60,90,120 min after MG injec-tion.Plasma MG concentration was measured in DNP model group and DNP control group by ELISA,while the protein levels of MG-modified proteins,brain-derived neurotrophic factor(BDNF),and its receptor TrkB in the spinal dorsal horn were detected by Western blot.Results Compared with DNP control group,PWT and PWL significantly decreased in DNP model group,at weeks 1,2,4(P<0.001),and plasma MG level increased at week 4(P<0.01);moreover,the protein levels of MG-modified proteins,BDNF,and TrkB in the spinal dorsal horn were significantly up-regulated at weeks 1,4(P<0.05).Compared with MG control group,PWT and PWL sig-nificantly decreased after administration in MG group(P<0.05).Conclusion MG accumulates in mice with DNP,along with pain hypersensitivity.MG can contribute to DNP-related central sensitization by up-regulating the BDNF/TrkB signaling pathway in the spinal dorsal horn,and may be a potential key pathogenic factor.