星形胶质细胞活化诱导慢性炎性痛小鼠抑郁样行为的机制探究OA

Objective:To investigate the behavioral changes and possible mechanisms of chronic inflammatory pain model mice induced by complete Freund's adjuvant(CFA).Methods:A total of 26 C57BL/6J male mice were randomly divided into the control group(Control group)and the CFA group(CFA model group).The CFA model group was injected with CFA into the right hindpaw plantar subcutanea to establish a chronic inflammatory pain model.The changes of mechanical pain threshold in the right plantar subcutanea were detected by Von Frey fibers,the activity of mice was detected by open field test,and the depression-like behavior of mice was detected by sugar spray test and forced swimming test.The expression of hippocampal astro-cyte marker GFAP and immature neuron marker DCX in the DG region were detected by immunohistochemistry.The expression of BDNF,TrkB,GFAP,NLRP3 inflammasome-related proteins in the hippocampus were detected by Western blot.Results:Compared to the Control group,the mechanical pain threshold of mice in the CFA model group was significantly decreased(P<0.001),the inner frame activity time and activity distance were significantly reduced(P<0.001),the back licking time was re-duced(P<0.001),and the forced swimming immobility time was prolonged(P<0.001).The number of GFAP-positive cells in the hippocampus was significantly increased(P<0.001),and the number of DCX-positive cells in the DG region was significantly reduced(P<0.001).At the same time,the protein expression of BDNF(P<0.001)and TrkB(P<0.001)in the hippocampus was significantly reduced,while the protein expression of GFAP(P<0.001),NLRP3(P<0.001),ASC(P<0.01),Caspase-1(P<0.05),IL-1β(P<0.001)and IL-18(P<0.001)was significantly increased.Conclusion:Chronic inflammatory pain can cause depression-like behavior in mice,and its mechanism may be related to the activation of hippocampal astrocytes induced by chronic inflammatory pain,promoting inflammation in the central nervous system,and inhibiting neurogenesis.