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鞘内注射芬太尼与电针合用对大鼠慢性炎性痛的镇痛效果
时间：2010-08-24 09:09:41 来源： 作者：
| The influence of hyperalgesia effect of electroacupuncture combined with fentannyl on chronic inflammatory rats ZHU Wen-zhi ,WANG Guo-lin ,YU Yong-hao. Department of Anesthesiology, Gengeral Hospital, Tianjin Medical University, Tianjin 300052, China [Abstract] Objective: To investigate the antinociceptive effect of electroacupuncture combined with fentanyl in the chronic inflammatory rats and the related mechanisms. Methods: The arthritis model was established by injection of complete Freund's adjuvant 0.05 ml into the right ankle joint of rats. 30 adult SD rats weighing 200～250g were randomly divided into five groups , 6 rats in each groups,including nomal control group, CFA group, EA group, fentanyl group and the combined application group.The nomal control group did not undergo any treatment. From the 1th day to the 7th day of the experiment, 1µg fentanyl(25µl) was injected intrathecally daily in fentanyl group and the combined application group，while 25µl normal saline was injected intrathecally in CFA group. On days 1 and 4 of the experiment, Han’s acupoint nerve stimulator(HANS) was connected to the needles inserded into the acupoints “yanglingquan”and “zusanli”with the parameters(intensity≤ 2mA, frequency 2/100Hz,30min each time).Recorded the changs of hyperalgesia score which was the difference of two hind paws withdrawal lantency on hot plate and examined the change of the quantity of through capillary electrophoresis(CE) and the expression of substance P in the spinal dorsal horn by the immunochemistry. Results: The quantity of glutamate in the lumbar spinal cord and the expression of SP in the spinal dorsal horn in the CFA group were higher than that of the other groups, while the hyperalgesia scores were lower .These changes of the CFA group had the statistical significance compared with the other groups (P<0.05 or 0.01).Compared with the EA group and fentanyl group, the quantity of glutamate and the expression of SP of the combined application group decreased and the hyperalgesia score was elevated significantly (P<0.05 or 0.01). Conclusion:Fentanyl can strengthen the antinociceptive effect of electroacupuncture ; the combined application attenuate the central sensitization to some extent. [Key words] Chronic inflammatory pain; Fentanyl; Electroacupuncture; Glutamate; Substance P 慢性炎性痛是一类常见的病理性疼痛，与中枢敏化及突触可塑性发生改变有关[1]，其中兴奋性递质谷氨酸（glutamate,Glu）及P物质（substance P,SP）对慢性炎性痛的形成和维持起着重要作用[2]。芬太尼是临床上常见的阿片类镇痛药,作用于体内阿片μ受体发挥作用，有实验证实腹腔注射芬太尼配合电针刺激可以提高痛阈[3]，而鞘内给予芬太尼合并电针的镇痛效果则尚需进一步探讨。本研究拟观察鞘内给予芬太尼和电针合用对大鼠慢性炎性痛的镇痛效果，探讨其可能机制，为临床治疗提供理论依据。 材料和方法 试剂和设备 完全弗氏佐剂( 批号01585, sigma公司,美国)。芬太尼 (批号040601,天津药物研究院药业有限公司)。SP一抗（sigma公司,美国）；毛细管电泳分析标准品glutamic acid （Beckman公司,美国）。LH202H韩氏穴位神经刺激仪，YLS-68智能热板仪（安徽淮北正华生物仪器设备有限公司），P／ACE 5010毛细管电泳仪(Beckman／Coulter公司,美国)。 动物及分组 健康成年雌性SD大鼠30只 (天津市动物中心)，体重200250g，随机分为5组（n=6）: 对照组（A组，不给予任何处理）、致炎组（B组，鞘内注射生理盐水25µl连续1周，每天1次）、电针组（C组，给药处理的第1天和第4天，采用电针仪电针大鼠“阳陵泉”和“足三里”两穴，强度≤2mA,频率2/100Hz，时间30min）、芬太尼组（D组，鞘内给25µl芬太尼,剂量1µg，每天1次,连续1周）和针药合用组（E组，处理与给药方法同C组、D组）。 关节炎模型建立及判断标准 大鼠右侧踝关节内注射弗氏佐剂50 µl致痛后，34h患侧关节出现红肿，大鼠出现自主活动减少，频繁舔拭并抬高患肢等伤害性行为，表明关节炎模型建立成功 [4]。关节炎大鼠模型建立后观察3天，痛阈稳定，第4天开始给药，连续7天。 测痛方法 给药第1天始,采用YLS-68智能热板仪，于每日9：00测定大鼠双后肢缩脚潜伏期（paw withdrawal latency,PWL）,计算痛敏分数（秒，s）=患侧缩脚潜伏期-对照侧缩脚潜伏期，连续观察7天。 置管方法 置管方法按照参考文献[5]方法。 针刺方法 给药第1、4天,在安静环境中，室温20℃，将大鼠躯干固定在特定筒架上，后肢暴露。待大鼠静止20min后，在大鼠右后肢的“足三里”和“阳陵泉”两穴上插人电针，以HANS电针治疗仪给予2/100Hz疏密波，强度以引起大鼠右后肢轻度抖动为宜(<2 mA)，持续30 min。 标本制备 给药第7天,大鼠在10%的水合氯醛液按0.0375㎎.㎏-1腹腔麻醉状态下，尽快取出脊髓L4-6段，一部分在放在液氮里冻存用于谷氨酸含量的分析。另一部分放于固定液（4％多聚甲醛)中固定6-12h，经梯度酒精脱水，二甲苯透明, 石蜡包埋,作连续冠状切片,切片厚5µm，用于免疫组化染色分析。 SP表达的测定 采用免疫组化染色SP法观察脊髓背角SP的表达。应用北京航空航天大学图像中心研制的CMIAS多功能真彩色病理图像分析系统，对免疫组化染色阳性反应物的积分光密度值进行统计分析。每个动物双侧脊髓L4～6背角各取4张连续切片，在400倍的光镜下对染色的免疫反应阳性物质进行图像分析处理。 表1 各组痛敏分数的比较（n=6, ±s）
9 张秀琳，朱崇斌，吴根诚等.大鼠侧脑室及鞘内注射孤啡肽减弱芬太尼镇痛效应.中国要药理学通报,1997,13:422-424. 10 管忍, 徐建国, 李伟彦.大鼠孤啡肽与吗啡的交叉耐受性.第二军医大学学报,2002,23:1363-1365. 11 Ohtori S, Takahashi K, Ino H,et al. Up-regulation of substance P and NMDA receptor mRNA in dorsal horn and preganglionic sympathetic neurons during adjuvant-induced noxious stimulation in rats. Ann Anat, 2002 ,184:71-76. 12 Khasabov SG, Rogers SD, Ghilardi JR, et al.Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci, 2002, 22:9086-9098. 13 Salter MW. Cellular neuroplasticity mechanisms mediating pain persistence. J Orofac Pain, 2004 ,18:318-324. 14 Herrero JF, Laird JM, Lopez-Garcia JA.Wind-up of spinal cord neurons and pain sensation: much ado about something? Prog Neurobiol, 2000 ,61:169-203. |
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