S1PR1在瑞芬太尼诱发切口痛大鼠痛觉过敏中的作用:与背根神经节KCNQ2/3钾通道的关系
Role of S1PR1 in remifentanil-induced hyperalgesia in rats with incisional pain:relationship with KCNQ2/3 potassium channels in dorsal root ganglia
殷玲 1宋振华 1靳晓迪 1李清 1于泳浩 1王春艳1
作者信息
- 1. 天津医科大学总医院麻醉科 天津市麻醉学研究所,天津 300052
- 折叠
摘要
目的 评价鞘氨醇-1-磷酸受体1(S1PR1)在瑞芬太尼诱发切口痛大鼠痛觉过敏中的作用及其与背根神经节KCNQ2/3钾通道的关系.方法 取尾静脉置管成功的雄性SD大鼠48只,2～3月龄,体质量260～280 g,采用随机数字表法分为6组(n=8):对照组(C组)、S1PR1抑制剂组(FTY720)组(F组)、瑞芬太尼组(R组)、瑞芬太尼+S1PR1抑制剂(FTY720)组(RF组)、瑞芬太尼+切口痛组(RI组)和瑞芬太尼+切口痛+S1PR1抑制剂(FTY720)组(RIF组).C组静脉输注生理盐水0.1 ml·kg-1·min-1 60 min;F组在生理盐水注射前10 min鞘内注射FTY720 3 nmol,尾静脉输注生理盐水 0.1 ml·kg-1·min-1 60 min;R 组尾静脉输注瑞芬太尼 1.0 μg·kg-1·min-1 60 min;RF组静脉输注瑞芬太尼1.0μg·kg-1·min-1 60 min前10 min鞘内注射FTY720 3 nmol;RI组建立大鼠切口痛模型,尾静脉输注瑞芬太尼1.0 μg·kg-1·min-1 60 min;RIF组瑞芬太尼输注前10 min鞘内注射FTY720 3 nmol,随后制备大鼠切口痛模型,同时尾静脉输注瑞芬太尼1.0 μg·kg-1·min-1 60 min.于输注瑞芬太尼或生理盐水前24 h(T0)、停止输注瑞芬太尼或生理盐水后2、6、24和48 h(T1-4)时测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL).最后一次测定痛阈后处死大鼠,取L4-6节段背根神经节组织,分别采用Western blot法和实时定量PCR法测定背根神经节S1PR1、KCNQ2和KCNQ3及其mRNA的表达.结果 与C组比较,R组和RI组T1-4时MWT降低,TWL缩短,背根神经节S1PR1及其mRNA表达上调,KCNQ2和KCNQ3及其mRNA表达下调(P＜0.05),F组各指标差异无统计学意义(P＞0.05);与R组比较,RI组T1-4时MWT降低,TWL缩短,背根神经节S1PR1及其mRNA表达上调,KCNQ2和KCNQ3及其mRNA表达下调,RF组T1-4时MWT升高,TWL延长,背根神经节S1PR1表达下调,KCNQ2和KCNQ3表达上调(P＜0.05);与RI组比较,RIF组T1-4时MWT升高,TWL延长,背根神经节S1PR1及其mRNA表达下调,KCNQ2和KCNQ3及其mRNA表达上调(P＜0.05).结论 S1PR1参与了瑞芬太尼诱发切口痛大鼠痛觉过敏形成的过程,与抑制背根神经节KCNQ2/3钾通道表达有关.
Abstract
Objective To evaluate the role of sphingosine-1-phospho-1 receptor 1(S1PR1)in remifentanil-induced hyperalgesia in rats with incisional pain and the relationship with KCNQ2/3 potassium channels in the dorsal root ganglia(DRG).Methods Forty-eight male Sprague-Dawley rats with successful caudal vein catheterization,aged 2-3 months,weighing 260-280 g,were divided into 6 groups(n=8 each)using a random number table method:control group(group C),S1PR1 inhibitor group(FTY720)group(group F),remifentanil group(group R),remifentanil+S1PR1 inhibitor(FTY720)group(group RF),remifentanil+incision pain group(group RI)and remifentanil+incision pain+S1PR1 inhibitor(FTY720)group(group RIF).In group C,normal saline 0.1 ml·kg-1·min-1 was intravenously infused for 60 min.In group F,FTY720 3 nmol was intrathecally injected at 10 min before normal saline injection,and 0.1 ml·kg-1·min-1 normal saline was infused into the caudal vein for 60 min.Remifentanil 1.0μg·kg-1·min-1 was infused for 60 min through the caudal vein in group R.In RF group,FTY720(3 nmol)was intrathecally injected,and 10 min later remifentanil 1.0 μg·kg-1·min-1 was infused via the caudal vein for 60 min.The incisional pain model was established,and remifentanil 1.0 μg·kg-1·min-1 was infused via the caudal vein for 60 min in RI group.In RIF group,FTY720 3 nmol was intrathecally in-jected at 10 min before remifentanil infusion,then the incisional pain model was developed,and remifen-tanil 1.0 μg·kg-1·min-1 was infused via the caudal vein at the same time for 60 min.The mechanical paw withdraw threshold(MWT)and thermal paw withdraw latency(TWL)were measured at 24 h before remifentanil or normal saline infusion(T0)and 2,6,24 and 48 h after remifentanil or normal saline infu-sion(T1-4).The rats were sacrificed after the last measurement of pain threshold,and theL4-6segments of the DRG were taken for determination of the expression of S1PR 1,KCNQ2 and KCNQ3 protein and mRNA in the DRG by Western blot and real-time polymerase chain reaction.Results Compared with group C,the MWT was significantly decreased,and the TWL was shortened at T1-4,the expression of S1PR1 protein and mRNA in the DRG was up-regulated,the expression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was down-regulated(P＜0.05),and no significant change was found in each parameter in R and RI groups(P＞0.05).Compared with group R,the MWT was significantly decreased,and the TWL was shortened at T1-4,the expression of S1PR1 protein and mRNA in the DRG was up-regulated,and the expression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was down-regulated in group RI,and the MWT was significantly increased,and the TWL was prolonged at T1-4,the expression of S1PR1 protein and mRNA in the DRG was down-regulated,and the expression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was up-regulated in group RF(P＜0.05).Compared with group RI,the MWT was significantly increased,and the TWL was prolonged at T1-4,the expression of S1PR1 protein and mRNA in the DRG was down-regulated,and the ex-pression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was up-regulated in group RIF(P＜0.05).Conclusions S1PR1 is involved in the process of remifentanil-induced hyperalgesia in rats with incisional pain,which is related to the inhibition of KCNQ2/3 potassium channel expression in the DRG.
关键词
鞘氨醇-1-磷酸受体/瑞芬太尼/痛觉过敏/神经节,脊/KCNQ钾通道Key words
Sphingosine-1-phosphate receptors/Remifentanil/Hyperalgesia/Ganglia,spi-nal/KCNQ potassium channels引用本文复制引用
基金项目
国家自然科学基金(81600962)
天津市自然科学基金面上项目(18JCYBJC94400)
出版年
2024
NETL
NSTL
万方数据