| Objective:Through the comparison of the analgesic effect of cyclooxygenase(COX)inhibitor——flurbiprofen axetil(FA)pretreatment on a rat model of incisional pain to observe the expression of ?-endorphin in spinal cord and hypothalamic arcuate nucleus(ARC)and to study the central mechanism of FA on postoperative pain.Methods:90 normal male SD rats(weighing 180–230 g)were selected after the measurement of paw mechanical withdrawal threshold(PMWT)with electronic von Frey.The rats were randomly divided into five groups(n=18): sham operation group(group S,rats were carried out sham operation that consisted of the injection of placebo 1 ml from tail vein and 5 minutes inhalation of 1% sevoflurane 30 minutes later),model group(Group C,30 minutes after the injection of placebo 1 ml,the rats underwent surgical incision that were anaesthetized with 1%sevoflurane),group of different dose of FA: low FA dose group(Group LF,30 minutes after the injection of3mg/kg FA 1 ml,the rats underwent surgical incision that were anaesthetized with1%sevoflurane),middle FA dose group(group MF,30 minutes after the injection of6mg/kg FA 1 ml,the rats underwent surgical incision that were anaesthetized with1%sevoflurane),high FA dose group(group HF,30 minutes after the injection of12mg/kg FA 1 ml,the rats underwent surgical incision that were anaesthetized with1%sevoflurane).At 1hour(T1),6hours(T2),12hours(T3)after operation,rats in each group were randomly divided to take the blood from the left ventricle,spinal cord and ARC under deep anesthesia with 40mg/kg 3% pentobarbital sodium after the measurement of the PMWT respectively.The concentration of inflammatory factors such as TNF-?,IL-1?,IL-6 and IL-10 and ?-endorphin in the serum were measured by using ELISA method.The spinal cord and ARC specimens were used for ELISA and immunohistochemistry test for ?-endorphin.The relative expression of pre-proopiomelanocortin(POMC)mRNA in the spinal cord and ARC were measured by using quantitative polymerase chain reaction(RT-qPCR).Results:(1)PMWT: compared with group S,PMWT in group C at each time point was significantly reduced;compared with group C,PMWT in groupLF,MF and HF at each time point was increased and proportional to dose(P< 0.05).(2)Levels of inflammatory factors and ?-endorphin in serum: compared with group S,levels of TNF-?,IL-1? and IL-6 in group C were increased,level of ?-endorphin was increased at T1 and decreased at T2,T3(P<0.01);compared with group C,level of IL-10 in group LF,MF and HF were increased at three time points and proportional to dose,levels of TNF-?,IL-1? and IL-6 in group LF,MF and HF were decreased and inversely proportional to dose(P<0.05),levels of ?-endorphin in group LF,MF and HF were decreased at T1 and they in group MF and HF were increased at T2,T3,and they in group LF were increased at T3(P<0.05).The levels were proportional to dose(P<0.05).(3)Levels of ?-endorphin in spinal cord and ARC: compared with group S,the level of ?-endorphin in spinal cord in group C was decreased at T2,T3 and the level in ARC was increased at T1(P<0.01);compared with group C,levels of ?-endorphin in spinalcord and ARC in group LF,MF and HF were increased at any time and proportional to dose(P< 0.05).(4)Relative expressions of POMC mRNA in the spinal cord and ARC: compared with group S,the relative expressions of POMC mRNA in the spinal cord and ARC in group C were increased(P<0.01);and between group LF,MF and HF,the relative expressions of POMC mRNA in the spinal cord and ARCwereproportional to dose(P<0.05).Conclusion:Pretreatment of COX inhibitor in a rat modal of incisional pain provides a favorable analgesic effect.And the effect may be related to the reduction of inflammatory reaction and the improvement of the level of ?-endorphin in periphery and spinal cord,ARC. |
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