CAJ | 학술논문

目的探讨切口痛-瑞芬太尼痛党过敏大鼠脊髓NMDA受体功能与δ阿片受体的关系.方法鞘内置管及尾静脉置管成功的雄性SD大鼠30只,体重260 ～ 280 g,2～3月龄,采用随机数字表法分为3组(n=10):对照组(C组)经尾静脉输注生理盐水0.1 ml·kg-·min-60 min;瑞芬太尼+切口痛组(RI组)经尾静脉输注瑞芬太尼1.0 μg·kg-1 ·min-1 60 min,于输注即刻建立切口痛模型;δ阿片受体抑制剂纳曲吲哚组(NI组)鞘内注射30 nmol纳曲吲哚溶液10μl,随后经尾静脉输注瑞芬太尼1.0μg· kg-·min-60 min,于输注即刻建立切口痛模型.于静脉输注生理盐水或瑞芬太尼前24 h、输注结束后2、6、24和48 h(T0-4)时测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL).T4时行为学测试结束后处死大鼠,取脊髓L4-6节段,采用Western blot法测定脊髓总蛋白和膜蛋白NMDA受体的表达水平,并计算膜蛋白和总蛋白NMDA受体表达的比值(m/t比值).结果与T0时比较,RI组和NI组T1-4时MWT降低,TWL缩短(P＜0.05);RI组和NI组T13时MWT逐渐降低,TWL逐渐缩短(P＜0.05),T3时与T4时MWT和TWL比较差异无统计学意义(P＞0.05).与C组比较,RI组和NI组T1-4时MWT降低,TWL缩短,脊髓总蛋白及膜蛋白含NR1亚基和NR2B亚基的NMDA受体表达上调,m/t比值均增加(P ＜0.05或0.01);与RI组比较,NI组T1-4时MWT升高,TWL延长,脊髓总蛋白及膜蛋白含NR1亚基和NR2B亚基的NMDA受体表达下调,m/t比值均降低(P＜0.05或0.01).结论脊髓δ阿片受体激活后可增强含NR1及NR2B亚基的NMDA受体功能,该作用可能参与了大鼠切口痛-瑞芬太尼痛觉过敏的形成.
목적 탐토절구통-서분태니통당과민대서척수NMDA수체공능여δ아편수체적관계.방법 초내치관급미정맥치관성공적웅성SD대서30지,체중260 ～ 280 g,2～3월령,채용수궤수자표법분위3조(n=10):대조조(C조)경미정맥수주생리염수0.1 ml·kg-·min-60 min;서분태니+절구통조(RI조)경미정맥수주서분태니1.0 μg·kg-1 ·min-1 60 min,우수주즉각건립절구통모형;δ아편수체억제제납곡신타조(NI조)초내주사30 nmol납곡신타용액10μl,수후경미정맥수주서분태니1.0μg· kg-·min-60 min,우수주즉각건립절구통모형.우정맥수주생리염수혹서분태니전24 h、수주결속후2、6、24화48 h(T0-4)시측정궤계축족반응역(MWT)화열축족잠복기(TWL).T4시행위학측시결속후처사대서,취척수L4-6절단,채용Western blot법측정척수총단백화막단백NMDA수체적표체수평,병계산막단백화총단백NMDA수체표체적비치(m/t비치).결과 여T0시비교,RI조화NI조T1-4시MWT강저,TWL축단(P＜0.05);RI조화NI조T13시MWT축점강저,TWL축점축단(P＜0.05),T3시여T4시MWT화TWL비교차이무통계학의의(P＞0.05).여C조비교,RI조화NI조T1-4시MWT강저,TWL축단,척수총단백급막단백함NR1아기화NR2B아기적NMDA수체표체상조,m/t비치균증가(P ＜0.05혹0.01);여RI조비교,NI조T1-4시MWT승고,TWL연장,척수총단백급막단백함NR1아기화NR2B아기적NMDA수체표체하조,m/t비치균강저(P＜0.05혹0.01).결론 척수δ아편수체격활후가증강함NR1급NR2B아기적NMDA수체공능,해작용가능삼여료대서절구통-서분태니통각과민적형성.
Objective To investigate the relationship between the function of spinal NMDA receptors and δ opioid receptors in a rat model of incisional pain-remifentanil-induced hyperalgesia.Methods Thirty male Sprague-Dawley rats,aged 2-3 months,weighing 260-280 g,in which intrathecal catheters were successfully implanted or in which the catheter was successfully placed via the caudal vein,were randomly divided into 3 groups (n =10 each) uisng a random number table:control gourp (group C),remifentanil + incisional pain group (group RI),and δ opioid receptor inhibitor naltrindole group (group NI).A 1-cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the hindpaw in chloral hydrate-anesthetized rats.In group C,normal saline 0.1 ml· kg-1 · min-1 was infused via the caudal vein for 60 min.In group RI,remifentanil 1.0 μg· kg-1 · min-1 was infused via the caudal vein for 60 min,and the model of incisional pain was established immediately at the beginning of infusion.In group NI,naltrindole 30 nmol (10 μl) was administrated intrathecally,then remifentanil was infused for 60 min at a rate of 1.0 μg· kg-1 · min-1 and the model of incisional pain was established immediately at the beginning of infusion.At 24 h before normal saline or remifentanil infusion and 2,6,24 and 48 h after the end of infusion (T0-4),mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last behavioral test.L4-6 segments of the spinal cords were removed for determination of NMDA receptor expression in total and membrane protein using Western blot analysis.The ratio of NMDA receptor expression in membrane protein to that in total protein (m/t ratio) was calculated.Results Compared with the basline value at T0,MWT was significantly decreased,and TWL was shortened at T1-4 in RI and NI groups.MWT was gradualy decreased,and TWL was gradualy shortened at T1-3 and no significant difference was found between MWT and TWL at T3 and T4 in RI and NI groups.Compared with group C,MWT was significantly decreased,and TWL was shortened at T1-4,the expression of NR1-and NR2B-containing NMDA receptors in total and membrane protein was down-regulated,and m/t ratio was decreased in group NI.Conclusion Activation of δ opioid receptors can enhance the function of NR1-and NR2B-containing NMDA receptors,which may be involved in the development of incisional pain-remifentanil-induced hyperalgesia in rats.