Objective To explore the role of dorsomedial hypothalamic nucleus(DMH)in chronic inflammatory pain,and to study whether mitochondrial calcium uniporter(MCU)is involved in pain modulation.Methods Male C56BL/6 mice were injected with complete Freund's adjuvant(CFA)or normal saline in the left foot to establish the experimental model.After 3 d,samples were collected for immunofluorescence staining of MCU and c-Fos.An MCU agonist(spermine)was injected into bilateral DMH at the early stage of pain(3 d after modeling)and at the late stage of pain(14 d after modeling),and tests for anxious behavior and/or pain behavior were performed 60 min following administration.Results CFA-induced chronic inflammatory pain markedly activated DMH neurons(P＜0.01),while MCU expression did not exhibit a significant increase.More interestingly,the activation of MCU significantly increased the static mechanical foot retraction threshold and dynamic mechanical foot retraction score in CFA mice(P＜0.01),and alleviated anxiety in a short time(P＜0.05,P＜0.01).Conclusion DMH is involved in the modulation of chronic inflammatory pain and related anxiety.The exogenous administration of the MCU specific agonist spermine in DMH significantly mitigated chronic inflammatory pain,which may be related to the unique channel closure characteristics of MCU at low intracellular calcium ion thresholds.
维普
万方数据
