Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation
OBJECTIVE To study the improvement effect and mechanism of sanguinarine(SG)on inflammatory pain in rats with lumbar disc herniation(LDH)and its mechanism.METHODS LDH model rats were established and divided into model group,SG low-dose,medium-dose and high-dose groups(1.00,2.50,6.25 mg/kg),high-dose of SG+Anisomycin[mitogen-activated protein kinase(MAPK)activator]group(6.25 mg/kg SG+5 mg/kg Anisomycin),with 10 rats in each group.Another 10 rats were included as the control group.Each group was given corresponding drugs intraperitoneally,while the control group and model group were given an equal volume of normal saline intraperitoneally,once a day,for 7 consecutive days.The general situation and neurological changes of rats in each group were observed,and the pain threshold[including paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)]of rats was determined;the histopathological changes of dorsal root ganglion(DRG)were observed in rats.The serum levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)]and pain factors[neuropeptide Y(NPY),5-hydroxytryptamine(5-HT)]in rats were detected.The positive expressions of ionized-calcium binding adaptor molecule-1(Iba-1)in spinal cord microglia and glial fibrillary acidic protein(GFAP)in astrocytes were observed.The expressions of proteins related to MAPK/extracellular signal-regulated kinase(ERK)/nuclear factor κB(NF-κB)signaling pathway,TNF-α and IL-1β proteins were detected in DRG tissue of rats.RESULTS Compared with the control group,the rats in the model group showed decreased appetite,hindlimb movement disorders,and disordered neuronal cell arrangement,the neurological score,the levels of TNF-α,IL-1β,NPY,the positive expressions of Iba-1 and GFAP,the phosphorylations of p38 MAPK,ERK1/2 and NF-κB p65,the protein expressions of TNF-α and IL-1β were significantly increased(P＜0.05);PWMT,PWTL and the levels of 5-HT were significantly reduced(P＜0.05).Compared with the model group,the rats of SG groups showed some relief in their mental appetite and hindlimb motor disorders,the intervertebral disc structure of DRG was restored,and the levels of the above quantitative indicators had significantly reversed(P＜0.05).Anisomycin reversed the improvement effect of SG on inflammatory pain in LDH rats.CONCLUSIONS SG can improve inflammatory pain by inhibiting the activation of microglia in DRG tissue of LDH rats,reducing the release of inflammatory factors,and increasing pain threshold,and its mechanism of action may be related to the inhibition of MAPK/ERK/NF-κB signaling pathway.
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