Effects Of Different Doses Of Parecoxib Sodium On Incision Pain And Spinal Glial Cells In Rats

Objective:This study mainly explores the effect and mechanism of intravenous administration of different doses of parecoxib sodium on incision pain in rats,and provides a reference for the clinical application of parecoxib sodium in wound pain.Methods:Seventy-two clean healthy adult male Waista rats,weighing 200-250g,8-10weeks old,were randomly divided into 9 groups（n=8）.Experimental animal groups:blank control group（group K）,preoperative group（group F）and postoperative group（group H）.Except for group K（only saline was injected into the tail vein）,the other groups were used to establish the model of incision pain in the paw and toe.Group F and group H were further divided into 4 subgroups,namely saline group（F1,H1）,parecoxib sodium 3,6 and 12 mg/kg groups（F2,F3,F4 and H2,H3,H4 groups,respectively）.Group F was injected with normal saline or parecoxib sodium 30 min before operation,and group H was injected with normal saline or parecoxib sodium 30 min after operation.The mechanical paw withdrawal threshold（MWT）was measured by CHAPLAN method at 30 min before operation（T₀）and 2,6,12,24 h after operation(T_1-4).After the behavioral test was completed at the preset time point,L4-6 right spinal dorsal horn tissue specimens were collected from each group of rats:Western Blot was used to detect the expression levels of spinal microglia markers（Ox42）and astrocytes markers（GFAP）;the levels of cyclooxygenase-2（COX-2）,interleukin-1β（IL-1β）,interleukin-6（IL-6）and tumor necrosis factor-α（TNF-α）in the spinal cord were measured by ELISA.Statistical analysis was performed using SPSS software,and P<0.05 was considered statistically significant.Results:1.Behavioral test results:At T₀,there was no significant difference in MWT between the groups（P>0.05）.There was no significant difference in MWT value of rats in group K at each time point（P>0.05）.Compared with group K,the MWT values of rats in group F1-4 and group H1-4 were significantly decreased at T_1-3（P<0.05）.However,there was no significant difference in MWT between F1-4 group and H1-4 group and K group at T₄（P>0.05）.Compared with group F1,the MWT values of rats in group F2-4 increased at T_1-3（P<0.05）.Compared with group H1,the MWT values of rats in group H2-4 increased at T_1-3（P<0.05）.Compared with group F2,the MWT values of rats in group F3-4 increased at T_1-3（P<0.05）.However,there was no significant difference between F3 group and F4 group（P>0.05）.Compared with group H2,the MWT values of rats in group H3-4increased at T_1-3（P<0.05）.However,there was no significant difference between H3 group and H4 group（P>0.05）.There was no significant difference in MWT between F1 and H1 groups（P>0.05）.At T_1-4,the rats in F2,F3 and F4 groups were significantly higher than those in H2,H3 and H4 groups（P<0.05）.2.Results of Western Blot:Compared with group K,there was no significant difference in the expression of Ox42 in spinal cord between groups F1 and H1（P>0.05）.The expression of GFAP in spinal cord was significantly up-regulated（P<0.05）.Compared with F1 group,there was no significant difference in the expression of Ox42 in spinal cord of rats in F2,F3 and F4 groups（P>0.05）.The expression of GFAP in spinal cord was significantly down-regulated（P<0.05）.Compared with H1group,there was no significant difference in the expression of Ox42 in spinal cord of rats in H2,H3 and H4 groups（P﹥0.05）.The expression of GFAP in spinal cord was significantly decreased（P<0.05）.There was no significant difference in the expression of Ox42 between F2,F3,F4 groups and H2,H3,H4 groups（P>0.05）.The expression of GFAP in F2,F3 and F4 groups was significantly lower than that in H2,H3 and H4 groups（P<0.05）.There was no significant difference in GFAP expression between F3 and F4 groups（P>0.05）.There was no significant difference in GFAP expression between H3 and H4 groups（P>0.05）.3.ELISA results:Compared with group K,the contents of COX-2,IL-1β,IL-6and TNF-αin spinal cord of rats in group F1 and H1 were significantly increased（P<0.05）.Compared with F1 group,the contents of COX-2,IL-1β,IL-6 and TNF-αin spinal cord of rats in F2,F3 and F4 groups were significantly decreased（P<0.05）.Compared with H1 group,the contents of COX-2,IL-1β,IL-6 and TNF-αin spinal cord of rats in H2,H3 and H4 groups were significantly decreased（P<0.05）.The contents of COX-2,IL-1β,IL-6 and TNF-αin spinal cord of rats in F2,F3and F4 groups were significantly lower than those in H2,H3 and H4 groups（P<0.05）.There was no significant difference in the content of COX-2,IL-1β,IL-6 and TNF-αin the spinal cord of F3 and F4 groups（P>0.05）.There was no significant difference in the contents of COX-2,IL-1β,IL-6 and TNF-αin spinal cord between H3 and H4 groups（P>0.05）.Conclusions:1.Intravenous administration of parecoxib sodium can increase pain threshold and reduce mechanical hyperalgesia in rats.2.The effect of parecoxib sodium intravenous administration 30 min before operation is better than that 30 min after operation in incision analgesia,the recommended dose was 6mg/kg among the doses of 3,6 and 12mg/kg.3.Parecoxib sodium intravenous administration can inhibit the expression of astrocyte marker（GFAP）,but has no significant effect on the expression level of spinal microglia marker（Ox42）in rats.4.The analgesic mechanism of parecoxib sodium intravenous administration in rats with incisional pain may be related to inhibiting the excessive activation of astrocytes in the spinal dorsal horn,blocking the release of inflammatory factors IL-1β,IL-6,TNF-α,etc.,and inhibiting the overexpression of COX-2,thereby affecting the synthesis of prostaglandins to reduce peripheral and central sensitization.