Study on the analgesic effect of neferine on neuropathic pain rats by regulating the HMGB1-RAGE signaling pathway
LI Xianchao
LUO Hongyu
Abstract：Objective To investigate the analgesic effect of neferine on neuropathic pain rats and the involvement of the high mobility group box-1(HMGB 1)-receptor for advanced glycation end-products(RAGE)signaling pathway.Methods Sprague-Dawley rats were randomly divided into sham operation group,model group,low-dose neferine group,high-dose neferine group,and high-dose neferine+rHMGB 1(recombinant protein HMGB1)group.A neuropathic pain rat model was established by ligating the spinal nerve.Mechanical stimulation and thermal sensitivity experiments were applied to detect pain behaviors in rats.Enzyme-linked immunosorbent assay was applied to detect levels of prostaglandin E2(PGE2),substance P(SP),serotonin(5-HT),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1 β),and IL-10.Grocott methenamine silver staining was applied to observe the morphological changes in rat spinal dorsal horn.The terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labelling staining was applied to observe apoptosis of spinal dorsal horn neurons.Western blot was applied to detect the protein levels of HMGB1,RAGE,nuclear factor-kappaB(NF-κB),p-NF-κB,B-cell lymphoma 2(Bcl-2),and Bcl-2-associated X protein(Bax)in spinal dorsal horn tissue.Results Compared with those of the control group,rats in the model group presented severe damages to the neural fiber structure,significantly lower paw retraction threshold,thermal sensitivity latency,IL-10 level and protein level of Bcl-2,but significantly higher levels of PGE2,SP,5-HT,TNF-α and IL-1β,apoptotic rate of spinal dorsal horn neurons,and protein expressions of HMGB1,RAGE,p-NF-κB/NF-κB and Bax(P＜0.05).Compared with those of model group,rats in the low-dose and high-dose neferine groups presented significantly alleviated damages to the neural fiber structure,significantly higher paw retraction threshold,thermal sensitivity latency,IL-10 level and protein level of Bcl-2,but significantly lower levels of PGE2,SP,5-HT,TNF-α and IL-1β levels,apoptotic rate of spinal dorsal horn neurons,and protein expressions of HMGB1,RAGE,p-NF-κB/NF-κB and Bax(P＜0.05).The recombinant protein rHMGB 1 was able to partially reverse the therapeutic effect of neferine on neuropathic pain in rats(P＜0.05).Conclusion Neferine can reduce inflammatory and pain factor levels and apoptosis of spinal dorsal horn neurons in neuropathic pain rats by inhibiting the HMGB 1-RAGE signaling pathway,and thereby alleviates pain.
Keywords：neferinehigh mobility group box-1-receptor for advanced glycation end-products signaling pathwayneuropathic pain
Publication Date：2024-10-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 3056-3060 )