Effect of Celastrol on Neuropathic Pain Model Mice / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of celastrol on painful and the emotional of anxiety and depression comorbidity on neuropathic pain model animal and to explore its possible mechanism．Method:Mice were randomly divided into sham group， model group， pregabalin group(25 mg·kg-1)， low， medium and high-dose celastrol groups (5，10，20 mg·kg-1). The mice model of neuropathic pain were established by the L5 spinal nerve ligation (SNL). After successful modeling， the treatment groups were given intragastric administration， the sham group and the model group were given the same volume of warm water.Mechanical pain were detected by Von Frey tests， anxiety and depression behaviors were separately detected by the open field and the tail tailing experiments， the pathological changes of microglial cells in hippocampus of mice in each group were observed by immunohistochemical staining (IHC). The inflammation of BV2 microglial cell made by 1 mg·L-1 lipopolysaccharide (LPS). Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α (TNF-α). The expression levels of TNF-α protein were detected by immunofluorescence（IF） staining.Result:Compared with sham group， significant change of mechanical pain thresholds， anxiety and depression were detected in the SNL mice (P<0.05，P<0.01)， the significant decreases of the body size of hippocampal microglia (P<0.05). Compared with SNL model group， 20 mg·kg-1 celastrol significantly increased the 50% paw withdraw threshold and the time of the open feld tests (P<0.05，P<0.01)，and decreased the time of the tail tailing experiments in the SNL mice (P<0.05)， and the cell body area of hippocampal microglia in SNL mice was reduced (P<0.05). Experiment in vitro show， compared with control group， the expression of TNF-α mRNA and protein expression in LPS-induced BV2 microglia increased significantly from 2-4 h (P<0.05，P<0.01). Compared with the LPS group， after 100 nmol·L-1 celastrol administration， LPS-induced microglia inflammatory factor TNF-α mRNA and TNF-α protein expression were significantly decreased (P<0.01).Conclusion:Celastrol can relieve pain-emotion comorbidity on neuropathic pain model mice， and its mechanism may be related to the anti-inflammation in the central nerves system.