Effects And Mechanism Of Dexmedetomidine On Postoperative Analgesia In Nicotine-dependent Rates

Objective:To study the analgesic effect of dexmedetomidine on postoperative pain in nicotine-dependent rats and explore its mechanism.Methods:Part I(Establishing a nicotine dependence-withdrawal model): 12 SD male rats were randomly divided into two groups(n=6): nicotine group(N group)and normal saline group(NS group).Nicotine group(N group): subcutaneous injection of 0.5mg/kg nicotine twice a day for 14 days;Normal saline group(NS group): subcutaneous injection of normal saline(volume was the nicotine volume of rats of the same weight in the nicotine group),twice a day for 14 days.After 14 days,the change of MWT in nicotine group(N group)and normal saline group(NS group)was measured at 2h,12 h,24h and 48 h after stopping administration,and the difference of withdrawal response between the two groups was observed.Part Ⅱ:18 SD male rats were randomly divided into three groups(n=6),namely the nicotine group(N group),the nicotine + incision pain group(N +I group),and the nicotine + incision pain + dexmedetomidine intervention group(N +I+D group).Nicotine group(N group): 0.5mg/kg of nicotine was injected subcutaneously for 14 days.Nicotine + incision pain group(N+I): 0.5mg/kg of nicotine was injected subcutaneously for 14 days,and the incision pain model was established 1 hour after the last nicotine injection.Nicotine + incision pain + dexmedetomidine intervention group(N+I+D): 14 days after subcutaneous nicotine injection,the incision pain model was established after the last nicotine injection,and 50ug/kg dexmedetomidine was intraperitoneally injected 10-20 minutes before the establishment of the incision pain model.The mechanical withdrawal thresholds(MWT)of each group of experimental rats were measured at 2h,12 h,24h and 48 h after the establishment of the incision pain model,and the spinal cords of each group were taken 48 h after the establishment of the incision pain model to detect the P-ERK expression of the spinal cord by parallel Western blot.Results:Part I: Before administration,there was no significant difference in MWT between rats in the normal saline group(NS group)and the nicotine group(N group)(P>0.05).However,the MWT of the nicotine group(N group)was significantly lower than that of the normal saline group(NS group)at 2h,12 h,24h and 48 h after stopping administration(P<0.05).Withdrawal scores of rats in the nicotine group(N group)were significantly increased at the 16 th and 40 th h after discontinuation of administration,compared with those in the normal saline group(NS group)(P<0.05).Part Ⅱ:The MWT of the nicotine group(N group)and the nicotine + incision pain + dexmedetomidine intervention group(N+I+D group)was significantly higher than that of the nicotine + incision pain group(N+I group)at 2h,12 h,24h and 48 h after the successful establishment of the incision pain model.The difference was statistically significant(P<0.05).There was no significant difference in MWT between the nicotine + incision pain + dexmedetomidine intervention group(N+I+D group)and the nicotine + incision pain + dexmedetomidine intervention group(N+I+D group)at 2h,12 h,24h and 48 h after the successful establishment of incision pain model(P>,0.05).The expression of P-ERK in spinal cord neurons of rats in the nicotine + incision pain + dexmedetomidine intervention group(N+I+D group)was significantly down-regulated compared with that in the nicotine + incision pain group(N+I group),and the difference between the two groups was statistically significant(P<0.05).The expression of P-ERK in spinal cord neurons of rats in the nicotine group(N group)was significantly lower than that in rats in the nicotine + incision pain group(N+I group),and the difference was statistically significant(P<0.05).The expression of P-ERK in spinal cord neurons of rats in the nicotine + incision pain + dexmedetomidine intervention group(N+I+D group)was slightly down-regulated compared with that of rats in the nicotine group(N group),with no statistically significant difference(P>,0.05).Conclusion:Dexmedetomidine may relieve acute postoperative pain in nicotine-dependent rats by reducing the expression of P-ERK in spinal cord neurons.