Dezocine alleviates remifentanil-induced hyperalgesia via targeting the Toll-like receptor 4/nuclear factor kappa-B pathway
Objective To investigate the effect of dezocine on remifentanil-induced postoperative hyperalgesia and the underlying mechanism.Methods A total of 40 healthy male Sprague-Dawley(SD)rats were randomly divided into Control group(C group),incision pain group(I group),Remifentanil infusion + incision pain group(R+I group),remifentanil + Dezocine infusion + incision pain group(R+D+I group),with 10 rats in each group.Rats in C group were blank controls.Before modeling,rats in R+I group and R+D+I group were intravenously infused with remifentanil,and those in I group were intravenously infused with the same volume of normal saline.Subsequently,the left posterior plantar incision was made to construct the incision pain model in I group,R+I group and R+D+I group.Rats in the R+D+I group were pretreated with dezocine by tail vein injection before remifentanil infusion.Paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)before surgery and at different time points after operation were measured by behavioral tests.The contents of inflammatory factors,including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-10 in spinal cord dorsal horn were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA and protein expressions of Toll-like receptor 4(TLR4),nuclear factor kappa-B(NF-κB)and transient receptor potential ankyrin 1(TRPA1)in spinal cord dorsal horn were detected by quantitative real-time PCR(qRT-PCR)and Western blot,respectively.Results The rat model of remifentanil-induced postoperative hyperalgesia was successfully constructed.Compared with those in C group,rats in I group presented significantly lower PWT and PWL,higher contents of TNF-α and IL-1β,lower content of IL-10,and higher mRNA and protein expressions of TLR4,NF-κB and TRPA1 in spinal cord dorsal horn at different time points after operation(P<0.05).Compared with those in I group,rats in R+I group presented significantly lower PWT and PWL,higher contents of TNF-α and IL-1β,lower content of IL-10,and higher mRNA and protein expressions of TLR4,NF-κB and TRPA1 in spinal cord dorsal horn at different time points after operation(P<0.05).Compared with those in R+I group,rats in R+D+I group presented significantly higher PWT and PWL,lower contents of TNF-α and IL-1β,higher content of IL-10,and lower mRNA and protein expressions of TLR4,NF-κB and TRPA1 in spinal cord dorsal horn at different time points after operation(P<0.05).Conclusion Dezocine alleviates remifentanil-induced postoperative hyperalgesia by inhibiting the TLR4/NF-κB pathway,downregulating mRNA and protein expressions of TRPA1 and suppressing the inflammatory response in spinal cord dorsal horn.
万方数据
维普
