Target-analgesia Of Flurbiprofen Axetil In Operative Incision Tissure And Effect On Fos-protein Of Spinal Cord In Incision-induced Rats

Objective:To study target-analgesia of flurbiprofen axetil in operative incision and to discuss the possible mechanism.Method:48 250g-weight rats were randomly divided into 6 groups.The rats were established incision pain model by being operated according to Brennan s method after having been anesthetized by breathing in isoflurane except control 1 group, which were anesthetized by breathing in isoflurane only.20minnutes later,control group1(D1 group) and control group2(D2 group) were injected physiological saline by vena caudalis,the other 4 groups were injected flurbiprofen axetil 2mg/kg, 4mg/kg,8mg/kg,16mg/kg(K1,K2,K3,K4group) respectively.Behavioral study was performed when the rats came back to consciousness and 1 hour after injection.In the behavioral study,stepping behavior was evaluated 0-60 min after hind paw incision.2hours after vena caudalis injection,all the rats were anesthetized deeply by pentobarbital sodium-perito injection 100mg/kg,muscles of both hind paws were dissected,homogenated,centrifuged and supematant fluids were dissociate.The concentration of flurbiprofen and PGE₂ were detected by reversed phase high peformance liquid chromatography(RP-HPLC) and ELISA respectively.After these rats were perfused,L4-S1 sections of spinal cords were dissected,sliced by freezing and processed by immunostained with a rabbit polyclonal antiserum directed against c-fos,then the changes of FLI positive neurons in the dorsal horn were studied.Result:(1)Flurbiprofen axetil can decreased stepping behavior in a rat model of incision pain in dose-dependent manner.Incision-induced FLI positive neurons were mainly located in the superficial dorsal horn(laminaeâ… andâ…¡)ipsilateral to the incision.(2)Flurbiprofen axetil treatment markedly decreased the numbers of FLI positive neurons of dorsal horn in dose-dependent manner.Compared to the control 2 group,the differences were significant among the different dose group(P＜0.05).(3) Flurbiprofen axetil treatment presented the tendency of decreasing concentration of PGE₂ in the muscle of operated hind paw in dose-dependent manner.As for the concentration of PGE₂ in the muscle of un-operated hind paw,the differences among D1,D2,K1,K2,K3 were not significant,but the difference between K4 and D1 was significant.(4)In these groups of different dosage,the concentration of flurbiprofen in operative incision increased compared to that in the non-operative incision, especially in group K3 and K4,the difference was significant.The concentration of flurbiprofen in operative incision of different dosage increased in dose-dependent manner.The difference of concentrat ion of flurbiprofen in non-operative incisions of K1,K2,K3 was not significant,but the concentration of flurbiprofen in non-operative incision of K4 increased compared to that of K1.Conclusion:(1)The distribution of flurbiprofen axeti in operative incision was targeted. (2)Flurbiprofen axeti administration could suppress the incision-evoked nociceptive behaviors and decrease the expression of pain excitatory transmitter PGE₂ in operative incision;Flurbiprofen administration of low-dosage(≤8 mg/kg) did not decrease the expression of PGE₂ in normal muscle tissue,but that of high-dosage(≥16mg/kg) decreased the expression of PGE₂ in normal muscle tissue.(3)The Fos expression of spinal cord were suppressed by flurbiprofen axetil administration in dose-dependent manner.