CAPE Inhibits The Activation Of Microglia Through The P38 MAPK/NF-κB Pathway To Relieve Neuropathic Pain

Part one: Caffeic acid phenethyl ester attenuates neuropathic pain by suppressing the p38 MAPK/NF-κB signal pathway in microgliaObjective: To investigate the effects of CAPE on p38 MAPK/NF-κB signal pathway and downstream inflammatory factors in microglia cells in the CCI model,and the possible mechanism of CAPE in relieving neuropathic pain.Methods: Adult male CD-1 mice aged 6-8 weeks and weighing 18-22 g were selected and the neuropathic pain model was established by the method of chronic sciatic nerve constriction injury.Mechanical allodynia was determined by measuring the incidence of foot withdrawal in response to mechanical indentation of Von Frey.Western blot and immunofluorescence were used to detect the effects of CAPE on the activation of microglia in spinal cord.The effects of CAPE on p38 MAPK and NF-κB p65 in microglia were detected by western blot.The effects of CAPE on proinflammatory cytokines(TNF-α,IL-1β,IL-6)in microglia were determined by RT-PCR.Results: The CCI model can induce the decrease of the mechanical threshold in mice,up-regulate the phosphorylation of p38 MAPK and NF-κB p65 in the spinal cord,activate spinal microglias,and increase the expression of pro-inflammatory cytokines(TNF-α,IL-1β,IL-6).CAPE relieved neuropathic pain behaviors induced by CCI.CAPE inhibited CCI-induced activation of microglia.Furthermore,CAPE suppressed the phosphorylation of p38 MAPK,inhibited the phosphorylation of NF-κB p65,and decreased the expression of pro-inflammatory cytokines(TNF-α,IL-1β,IL-6).Conclusion: CAPE can relieve neuropathic pain by inhibiting the p38 MAPK/NF-κB signal transduction pathway,inhibiting the activity of spinal microglia and down-regulating the expression of proinflammatory cytokines.CAPE may be a potential drug for neuropathic pain.Part two: Caffeic acid phenethyl ester inhibits LPS-induced inflammatory response by suppressing the p38 MAPK/NF-κB signal pathway in microgliaObjective: To investigate the effects of CAPE on p38 MAPK/NF-κB signal pathway and downstream inflammatory factors in microglia cells cultured in vitro,and the possible mechanism of CAPE in inhibiting inflammatory response.Methods: BV2 cells were selected.The effects of CAPE on p38 MAPK and NF-κB p65 in microglia cultured in vitro were detected by western blot and immunofluorescence.The effects of CAPE on proinflammatory cytokines(TNF-α,IL-1β,IL-6)in microglia cultured in vitro were determined by RT-PCR.Results: LPS can up-regulate the phosphorylationof p38 MAPK,promote the translocation of NF-κB p65 and increase the expression of pro-inflammatory cytokines(TNF-α,IL-1β,IL-6).Meanwhile,CAPE inhibited the phosphorylation of p38 MAPK and translocation of NF-κB p65,and inhibited the up-regulated expression of proinflammatory cytokines in microglia cultured in vitro.Conclusion: CAPE can relieve neuropathic pain by inhibiting the p38 MAPK/NF-κB signal transduction pathway,inhibiting the activity of spinal microglia and down-regulating the expression of proinflammatory cytokines.CAPE is an effective and safe drug that may be a potential drug for neuropathic pain.