The Study Of The Role And Mechanisms Of Spinal ?-opioid Receptor In Remifentanil-induced Postoperative Hyperalgesia In Rats

Objective To investigate the role and mechanisms of spinal ?-opioid receptor(KOR)in remifentanil-induced postoperative hyperalgesia in rats.Methods Thirty-Six adult male Sprague Dawley rats(weight 230 ~ 270g),in which intrathecal catheters were implanted successfully,were randomly divided into 6 groups(n = 6 each): including control group(group C),incisional pain group(group I),remifentanil group without incision(group R),remifentanil group with incision(group RI),?-opioid receptor agonist U50488 H group(group URI)and ?-opioid receptor antagonist nor-BNI + U50488 H group(group NURI).Except group C and group R,rats in other groups were performed right hind paw incision.Except group C and group I,rats in other groups were continuously infused remifentanil 10 ?g·kg-1·min-1 for 1h by tail vein.Rats in group URI were injected intrathecally U50488 H 5 ?g/10 ?l at 30 min before remifentanil infusion.Rats in group NURI were received intrathecal injection of nor-BNI 15 ?g/10 ?l at 30 minutes before U50488 H was intrathecally injected at 30 min before remifentanil infusion.Paw withdrawl threshold(PWT),paw pressure whithdrawl threshold(PPW),and paw withdrawl lentency(PWL)were measured in both hind paws before implanting intrathecal catheter,before incision,at 1 h,4 h,1 d,2 d and 3 d after incision.The spinal lumbar enlargement were removed to determine the protein expression of KOR and the mRNA level of KOR by using western blot and real-time PCR techniques after finishing pain behavioral tests.Other thirty-Six adult male Sprague Dawley rats in which intrathecal catheters were implanted successfully,were randomly divided into 6 groups(n = 6 each)as the aboved same groups.All rats were recorded the C fiber-evoked filed potentials at the superficial layers of spinal dorsal horn at the lumbar enlargement from 60 mins before infusion of remifentanil to 180 mins after infusion.The long-term potentiation(LTP)in spinal dorsal horn evoked by remifentanil infusion and its area under the curve(AUC)were calculated.Results The PWT,PPW and PWL in both hind paws were significantly decreased at 2 d,3 d after incision in group R comparing with group C.The PWT,PPW and PWL in ipsilateral at 1 h ~ 3 d after incision were significantly decreased,and PWT,PPW,PWL in contralateral hind paw at 2 d,3 d after incision were significantly decreased in group RI comparing with group C(P < 0.05).The PWT,PPW and PWL in ipsilateral hind paw at 1d ~ 3d after incision and in contralateral hind paw at 2 d,3 d after incision were significantly decreased in group RI comparing with group I(P < 0.05).The PWT,PPW and PWL in ipsilateral hind paw at 1 h ~ 3 d after incision were significantly increased after incision,and PWT,PPW and PWL in contralateral hind paw were significantly increased at 2 d,3 d after incision in group URI comparing with group RI(P < 0.05).The PWT,PPW and PWL in ipsilateral hind paw were significantly decreased at each time points after incision and PWT,PPW and PWL in contralateral hind paw were significantly decreased at 2 d,3 d after incision in group NURI comparing with group URI(P < 0.05).The expression levels of KOR protein and mRNA were significantly decreased in group R and group RI comparng with group C(P < 0.05).The expression levels of KOR protein and mRNA were significantly decreased in group RI comparing with group I(P < 0.05).The expression levels of KOR protein and mRNA were significantly increased in in group URI comparing with group RI(P < 0.05).The expression levels of KOR protein and mRNA were significantly decreased again in group NUR comparing with group U(P < 0.05).LTP were recorded in group R,group RI,and group NURI,but not in group C,group I,and group URI.The AUC of C-fiber evoked field potentials were significantly increased in group R and group RI comparing with group C(P < 0.05).The AUC of C-fiber evoked field potentials were significantly increased in group RI comparing with group I(P < 0.05).The AUC of C-fiber evoked field potentials were significantly decreased in group URI comparing with group RI(P < 0.05).The AUC of C-fiber evoked field potentials were significantly increased in group NURI comparing with group URI(P < 0.05).Conclusion Remifentanil-exaggerated postoperative hyperalgesia in rats was related to down-regulation of spinal ?-opioid receptors.