| OBJECTIVES㈠Based on preemptive analgesia or not,preemptive analgesia group and control group were divided,and the efficacy and safty of preemptive intervention in total knee arthroplasty were assessed;㈡ Based on the change of inflammatory response indicators,to investigate the effect of selective COX-2 inhibitor Celecoxib for changes of inflammatory reaction in total knee arthroplasty analgesia.And the relationship between inflammatory changes and body pain and functional outcomes were demonstrated;㈢CFA induced inflammatory pain mouse model was constructed,the behavioral changes,related proteins changes in the expression of ERK1/2/CREB signaling pathway and mTOR/S6K signaling pathway were measured to detective the possible mechanism of preemptive analgesia on inflammatory response。METHODSFeb.2013-Feb.2014,seventy-five patients with unilateral total knee arthroplasty were followed-up.Of them,25 male and 50 female;the grade of ASA were Ⅰ-Ⅲ;age 68.3±6.5(54-76)years old.All patients were randomly divided into two groups:preemptive analgesia group and control group.The following parameters were used to evaluate analgesic efficacy:Range of motion,pain at rest,pain at walking,functional walking capacity(2MWT and 6MWT),WOMAC score and hs-CRP level.24 CFA induced inflammatory pain mouse models were constructed and randomly divided into three groups(Control group,CFA induced inflammatory model group and preemptive group,8 in each).The behavioral indexes(mechanical pain threshold,thermal latency and open field test)and related proteins changes in the expression of ERK1/2/CREB signaling pathway and mTOR/S6K signaling pathway were measured at 0,1,2,3,5,7day.RESULTS1.Compared with control group,the pain at rest and walking were less in preemptive analgesia group(P<0.05).No difference was found on the pain at rest and walking after 1 week between preemptive analgesia group and control group.Cumulative consumption of morphine of 48 hours postoperatively was 43.28±14.65 and 45.03±15.42mg in preemptive analgesia group and control group,there is no difference between these two groups(P=0.113).2.The hs-CRP level was lower in preemptive analgesia group,and return to normal level after 2 weeks.The hs-CRP level was lower in preemptive analgesia group after 1 week postopertively(P<0.05).No difference was found after 1 week(P>0.05).3.The hs-CRP level was positively correlated with pain at rest and walking(correlation coefficient 0.398/0.377,P=0.000,0.000),but negatively correlated with ROM(correlation coefficient-0.741,P=0.000).4.The 2MWT of all patients improved significantly postoperatively(P=0.000).The 2MWT was better in preemptive analgesia group(17.13±3.82VS 14.19±3.56,P=0.001),but no difference was found after 2 weeks(P=0.148,0.108).5.The 6MWT and WOMAC score improved significantly postoperatively(P=0.020,0.000).No difference was found between preemptive analgesia group and control group at 1 and 6 month postoperatively(P>0.058).6.Two variables were found independently and significantly correlated with the 2MWT,while three variables correlated with the 6MWT and WOMAC.Variance of hs-CRP between day 2 and 3 and VAS at rest of day 7 postoperatively were the independent predictors of 2MWT.Variance of hs-CRP between day 3 and 4,ROM at day 4 postoperatively and 2MWT preoperatively were the independent predictors of 6MWT.VAS at walking of day 1 and 2 and VAS pre operatively were the independent predictors of WOMAC.7.Compared with CFA induced inflammatory model group,the mechanical pain threshold were all higher in preemptive analgesia group at each time(P<0.05).And the thermal latency time was lower after 1 week(P=0.013).The results of open field test confirmed that preemptive analgesia could improve the behaviora ability,but with no significane in statistics.8.Compared with CFA induced inflammatory model group,the levels of p-ERKl/2(146.72 士 28.17%,P = 0.000)and p-CREB(109.86 士 19.22%,P=0.000)after 1 week were lower significantly.The levels of p-mTOR(156.54±13.41%,P=0.002)’p-4EBP(113.72±10.49%,P=0.001)、p-S6K(108.93±9.57%,P=0.000)and p-S6(152.87±13.65%,P = 0.000)were lower significantly also.CONCLUTIONS1.Preemptive analgesia can achieve good analgesic effect within 1 week postoperatively,ensuring early functional exercise of knee replacement surgery,but no long-term analgesic effect.Preemptive analgesia did not significantly increase the incidence of postoperative adverse drug reactions,and confirmed the safety of preemptive analgesia.2.Preemptive analgesia has a significant positive effect on the joint function,especially in 1 week.No correlation is found between the use of preemptive analgesia or not with long-term function and quality of life level.3.Inflammatory reaction intensity of preemptive analgesia group is lower than control group 1 week postoperatively,and returns to normal levels after 2 weeks.The inflammatory level of the body is significantly correlated with the function of the total knee arthroplasty,and the reasonable control of the body inflammation has a significant improvement in the prognosis of the patients after joint replacement.4.Variance of hs-CRP between day 2 and 3 and VAS at rest of day 7 postoperatively were the independent predictors of 2MWT.Variance of hs-CRP between day 3 and 4,ROM at day 4 postoperatively and 2MWT preoperatively were the independent predictors of 6MWT.VAS at walking of day 1 and 2 and VAS pre operatively were the independent predictors of WOMAC.5.The preemptive celexib analgesia could improve the behavioral indexes of CFA induced inflammatory pain mouse models.These results mightbe partially correlated with related proteins changes in the expression of ERK1/2/CREB signaling pathway and mTOR/S6K signaling pathway. |
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