CAJ | 학술논문

目的观察重复腹腔注射右美托咪定(DEX)对神经病理性疼痛大鼠的痛觉过敏和背根神经节(DRG)中ERK信号通路激活的影响.方法给坐骨神经部分结扎(PSNL)神经病理性疼痛大鼠重复腹腔注射不同剂量的DEX.观察各组大鼠的机械、热痛觉过敏阈值.行为学测试完成后用免疫荧光和Western blot方法检测大鼠手术侧L5 DRG中p-ERK的表达.结果 (1)腹腔注射DEX 40 μg/kg 7、14 d均明显减轻PSNL诱导的机械、热痛觉过敏(P＜0.05).而腹腔注射DEX20μg/kg对PSNL大鼠疼痛行为学无明显影响.(2)重复腹腔注射40μg/kg DEX 7、14 d p-ERK的平均荧光强度比同一时间点的PSNL组明显减弱(P＜0.05),但仍明显高于对照组(P＜0.05).重复腹腔注射20μg/kg对PSNL大鼠p-ERK的平均荧光强度无明显影响(P＞0.05).(3)Westem blot 结果显示重复腹腔注射40μg/kg DEX 7、14 d明显抑制PSNL诱导的p-ERK的蛋白表达增多(P＜0.05).重复腹腔注射20μg/kg对PSNL大鼠p-ERK的蛋白表达无明显影响(P＞0.05).结论重复腹腔注射DEX能够减轻神经损伤引起的痛觉过敏,抑制外周初级感觉神经系统中ERK信号通路的激活可能是其缓解的疼痛症状的机制之一.
목적 관찰중복복강주사우미탁미정(DEX)대신경병이성동통대서적통각과민화배근신경절(DRG)중ERK신호통로격활적영향.방법 급좌골신경부분결찰(PSNL)신경병이성동통대서중복복강주사불동제량적DEX.관찰각조대서적궤계、열통각과민역치.행위학측시완성후용면역형광화Western blot방법검측대서수술측L5 DRG중p-ERK적표체.결과 (1)복강주사DEX 40 μg/kg 7、14 d균명현감경PSNL유도적궤계、열통각과민(P＜0.05).이복강주사DEX20μg/kg대PSNL대서동통행위학무명현영향.(2)중복복강주사40μg/kg DEX 7、14 d p-ERK적평균형광강도비동일시간점적PSNL조명현감약(P＜0.05),단잉명현고우대조조(P＜0.05).중복복강주사20μg/kg대PSNL대서p-ERK적평균형광강도무명현영향(P＞0.05).(3)Westem blot 결과현시중복복강주사40μg/kg DEX 7、14 d명현억제PSNL유도적p-ERK적단백표체증다(P＜0.05).중복복강주사20μg/kg대PSNL대서p-ERK적단백표체무명현영향(P＞0.05).결론 중복복강주사DEX능구감경신경손상인기적통각과민,억제외주초급감각신경계통중ERK신호통로적격활가능시기완해적동통증상적궤제지일.
Objective To investigate the effect of systemic administration of dexmedetomidine, a selective alpha 2 adrenergic receptor agonist, on mechanical and thermal hyperalgesia and dorsal root ganglia ERK activation induced by neuropathic pain. Methods Intraperitoneal injection of dexmedetomidine was repeatedly given once daily for 7 days or 14 days with the first injection one day before partial sciatic nerve ligation ( PSNL) surgery. Mechanical and thermal nociceptive thresholds were assessed in all animals. Then, animals were killed at corresponding time points, and the L5 DRG was removed for L5 DRG ERK activation status analysis by using immunoflurecence and Western blotting. Results (1) Partial sciatic never ligation produced a robust mechanical and thermal hyperalgisia and ERK activation of the L5 DRG in P7 and P14 groups. At the dose of 40 μg/kg, dexmedetomidine significantly attenuated PSNL-induced ipsilateral hyperalgesia on the day 7 and 14 after surgery. But the dose of 20 μg/kg of dexmedetomidine had no effect on pain behaviorl; (2) PSNL-induced up-regulation of mean fluorescence intensity of pERK on ipsilateral side of the L5 DRG was significantly suppressed by day 7, 14 post-PSNL following 40 μg/kg dexmedetomidine application, whereas 20 μg/kg dexmedetomidine had no effect; (3) Western blotting revealed that up-regulation of the protein expression of p-ERK on ipsilateral side of the L5 DRG was significantly inhibited on the day 7, 14 post-PSNL following 40 μg/kg dexmedetomidine application,whereas 20 μg/kg dexmedetomidine had no effect. Conclusion Systemic dexmedetomidine inhibits the activation of ERK signals in L5 DRG, which is possibly associated with its antihyperalgesia in rats with neuropathtic pain.