机构地区:[1]华中科技大学同济医学院附属同济医院麻醉学教研室,武汉430030
出 处:《中国疼痛医学杂志》2012年第11期688-692,共5页Chinese Journal of Pain Medicine
基 金:国家自然科学基金资助项目(No.30872440)
摘 要:目的 :观察鞘内注射δ阿片受体特异性拮抗剂对吗啡耐受大鼠慢性疼痛的疼痛行为学的影响,探讨吗啡耐受机制。方法 :选择鞘内置管成功SD大鼠在成功建模后第10天随机分为8组并给药:骨癌痛+生理盐水对照组(BC组)、骨癌痛+吗啡组(BM组)、骨癌痛+呐曲吲哚+吗啡组(BN组)、骨癌痛+DPDPE(D-丙2-D-亮5-脑啡肽,[D-Pen2,D-Cl-Phe5]-enkephalin,δ受体特异性激动剂)+吗啡组(BD组)、SNI(spared nerve injury,坐骨神经分支选择性损伤模型)+生理盐水对照组(SC组)、SNI+吗啡组(SM组)、SNI+呐曲吲哚+吗啡组(SN组)、SNI+DPDPE+吗啡组(SD组)。BC组和SC组鞘内注射10μl生理盐水,BM组和SM组鞘内注射10μg/10μl吗啡,BN组和SN组鞘内注射10μg/10μl呐曲吲哚20 min后加注10μg/10μl吗啡,BD组和SD组鞘内注射1μg/10μl DPDPE 20min后加注10μg/10μl吗啡。SNI模型大鼠1天两次给药,骨癌痛模型大鼠1天3次给药,连续9天。采用von Frey丝分别于建模前(基础状态),建模后3、5、7、9 d(T3、T5、T7、T9),鞘内给药1、4、7、9 d(I1、I4、I7、I9)时测定术侧机械痛阈。骨癌痛模型大鼠连续9天鞘内注药后灌注取左右两侧胫骨,冰冻切片,HE染色,观察肿瘤生长及骨结构破坏情况。结果 :HE染色显示种植侧胫骨癌细胞大量生长,异型性明显,骨质大片缺损,骨癌痛模型建模成功。两种慢性疼痛模型中,给药前各组大鼠机械阈值皆明显降低形成痛觉过敏(P<0.05);给药过程中,各治疗组均有镇痛作用,其大鼠机械阈值均明显升高(P<0.05);在给药第7天及第9天,大鼠机械痛阈较治疗第1天相比明显降低(P<0.05)。骨癌痛模型中,与BN组相比,BM组在第9天其机械阈值明显降低(P<0.05)。在SNI模型,与SN组相比,SM组及SD组其机械阈值在给药的第7、9天皆明显降低。结论 :鞘内注射δ阿片受体特异性拮抗剂呐曲吲哚可以抑制或延缓吗啡耐受,δ阿片受体参与吗啡耐受形成。Objective: To investigate the effect of intrathecal δ-opioid receptor antagonists specificity on morphine tolerance in rats with chronic pain,and to explore possible mechanism of morphine tolerance.Methods: Sprague-Dawley rats were successfully modeled with bone cancer pain or spared nerve injury(SNI),and then intrathecal catheters were placed in.The animals were randomly divided into eight groups: bone cancer pain +saline group(group BC),bone cancer pain +morphine group(group BM),bone cancer pain +naltrindole +morphine group(group BN),bone cancer pain +DPDPE +morphine group(group BD),SNI +saline group(group SC),SNI +morphine group(group SM),SNI +naltrindole +morphine group(group SN),SNI +DPDPE +morphine group(group SD).Rats in each group began to give medicine ten days after pain models were made.Group BC/SC and group BM/SM rats were accepted intrathecal injection(I.T.) of saline and 10 μg morphine which dissolved in 10 μl saline,respectively.In group BN/SN,intrathecal morphine 10 μg/10 μl was given 20 minutes after intrathecal naltrindole 10 μg/10 μl was administered,while rats in group BD/SD were accepted intrathecal DPDPE 1 μg/10 μl at first,and then intrathecal morphine 10 μg/10 μl was injected 20 minutes later.All SNI model rats were injected twice a day for 9 consecutive days,while bone cancer model rats were injected three times a day for 9 consecutive days.The mechanical allodynia was measured respectively at baseline and 3,5,7,9 days(T3,T5,T7,T9) after SNI or bone cancer pain model operation and 1,4,7,9 days(I1,I4,I7,I9) during injection of drugs.Heart perfusion by 4% paraformaldehyde was performed in the implantation rats after the last injection of drugs.Then bilateral tibias of rats were sliced into frozen sections and stained with H-E.Results: H-E stain showed that cells of the implantation tibia had absolutely pleomorphism and the bone defects were extensive.The bone cancer pain model was successful.All anima
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