Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund's adjuvant by inhibiting the activation of astrocytes in mice
Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin(PNS)on mouse models of chronic inflammatory pain caused by complete Freund's adjuvant(CFA).Methods A total of 48 male C57BL/6J mice were divided randomly into four groups:normal saline control group(Ctrl),CFA group(CFA),CFA+PNS group(CFA+PNS),CFA+dexamethasone(DEX)group(CFA+DEX).Von Frey filaments were used to detect mechanical pain in mice.Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein(GFAP)positive astrocytes.Western blotting was used to detect the expressions of GFAP,nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),Caspase-1,interleukin(IL)-1β,and IL-18 in mice's spinal cord segments in each group.Results Compared with the Ctrl group,mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1,day 3,day 5,day 7,and day 14.Additionally,there was a significant decrease in NLRP3,ASC,Caspase-1,IL-1β and IL-18 in the spinal cord of the mice.PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3,ASC,Caspase-1,IL-1β and IL-18 in the spinal cord of mice,with no significant difference compared with the CFA+DEX group.CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice,as measured by immunohistochemistry;PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord.According to Western blotting results,GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group;PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord.Conclusion PNS has a good alleviating effect on inflammatory pain,and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.
Panax notoginseng saponinsAstrocyteInflammatory painNucleotide-binding and oligomerization domain-like receptor thermal protein domain associated protein 3ImmunohistochemistryWestern blottingMouse
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