大鼠中缝大核内一氧化氮在痛觉调制和针刺镇痛中的作用(英文)

Role of nitric oxide in nucleus raphe magnus in pain regulation and electroacupuncture analgesia in rats

背景:L-精氨酸是内源性一氧化氮的前体物质,而一氧化氮参与外周脊髓水平和脊髓水平以上痛觉的调制。目的:探讨延髓中缝大核内一氧化氮在痛觉调制和针刺镇痛过程的作用。设计:以动物为观察对象的随机对照实验。单位:咸宁学院医学院生理教研室。材料:实验于2002-05/2003-03在咸宁学院医学院生理教研室完成。选用63只Wistar大鼠,随机分为7组,每组9只大鼠:①L-精氨酸量效关系实验分为5组:生理盐水组,L-精氨酸1,2,4,8mmol组。②L-精氨酸与电针镇痛关系实验分为两组:生理盐水+电针组,L-精氨酸+电针组。方法:①L-精氨酸量效关系实验:5组大鼠分别延髓中缝大核微量注射生理盐水及L-精氨酸1,2,4,8mmol,容积均为1.5μL。给药后每隔10min以(50±0.5)℃热水刺激甩尾测定痛阈,连续观察90min。②L-精氨酸与电针镇痛关系实验:两组大鼠分别延髓中缝大核微量注射生理盐水1.5μL及L-精氨酸8mmol(1.5μL),10min后电针刺激大鼠双侧后肢“足三里”(位,频率为4～16Hz,强度按1,2,3V顺序递增电压,每一强度电针10min,共电针30min并测痛3次,停针后继续每隔10min测痛1次,直至注药后90min。主要观察指标:各组大鼠不同时间点痛阈变化。结果:63只大鼠进入结果分析。①L-精氨酸1mmol组大鼠各个时间点痛阈低于生理盐水组,但统计学分析无差异(P>0.05),L-精氨酸2,4,8mmol组大鼠各个时间点痛阈均显著低于生理盐水组(P<0.001),作用持续至给药后80min;且随着浓度的增加,大鼠痛阈降低的幅度增加。②L-精氨酸+电针组大鼠给药后20～50min痛阈明显低于生理盐水+电针组(P<0.01)。结论:①延髓中缝大核微量注射L-精氨酸具有降低痛阈作用,其作用呈剂量依赖性。②电针能提高痛阈,L-精氨酸可削弱电针镇痛效应。③以上提示延髓中缝大核内一氧化氮参与痛和电针镇痛的病理生理过程,其含量增加明显降低痛阈。

BACKGROUND： L-arginine （L-Arg） is the precursor of endogenous nitric oxide （NO）, which joins the pain regulation of peripheral myeloid level and above. OBJECTIVE： To study the role and mechanism of NO in nucleus raphe magnus （NRM） in pain regulation and electroacupuncture analgesia. DESIGN： A random control experiment on rats. SETTING： Physiology Department of Medical College of Xianning College. MATERIALS： The experiment was done during May 2002 to March 2003 in the Physiology Department of Medical College of Xianning College. The 63 Wistar rats were randomized into 7 groups with 9 in each. ① Five groups for the experiment of L-Arg dose-effect relationship： Normal saline group and L-Arg 1, 2, 4, 8 mmol groups. ②. Two groups for the experiment of relationship between L-Arg and electroacupuncture analgesia： Norreal saline ＋ electroacupuncture group and L-Arg ＋ electroacupuncture group. METHODS： ① Experiment of L-Arg dose-effect relationship： Normal saline group was injected normal saline. L-Arg 1, 2, 4, 8 mmol groups were injected L-Arg 1, 2, 4, 8 mmol respectively. The volume was all 1.5 μL. Then, the hot water （50±0.5） ℃ was used to stimulate the tail once every 10 minutes to cause tail flick for testing the pain threshold. The observation was carried out continuously for 90 minutes. ②. Experiment of relationship between L-Arg and electroacupuncture analgesia： The two groups were injected normal saline and L-Arg 8 mmol respectively. The volume was all 1.5 μL. Ten minutes later, Zusanli （ST 36） of both posterior legs of rats were punctured with electric stimulation. The frequency was 4-16 Hz, and the intensity in an increasing order of 1, 2, 3V given 10 minutes of each. The electroacupuncture was totally 30 minutes, during which, testing the pain threshold 3 times. After needling, the pain threshold was still tested once every 10 minutes, till 90 minutes after injecting L-Arg. MAIN OUTCOME MEASURES： Pain threshold at different time points. RESULTS： The 63 rats entered the result analysis. ① The pain threshold of L-Arg 1 mmol group at all time points was lower than that of the normal saline group, but without statistical significance （P 〉 0.05）. The pain threshold of L-Arg 2, 4, 8 mmol groups was much lower than that of the normal saline group at all time points （P 〈 0.001）, and the effect was last- ing to 80 minutes after injecting L-Arg, and with the increase of L-Arg density, the amplitude of pain threshold lowering was increased. ② The pain threshold of L-Arg ＋ electroacupuncture group was much lower than that of the normal saline ＋ electroacupuncture group at the time points of 20-50 minutes （P 〈 0.01）. CONCLUSION： ① The L-Arg injection to NRM can lower the pain threshold and there is a dose-dependent effect in it. ②The electroacupuncture can raise the pain threshold, and the L-Arg injection can weaken the effect of electroacupuncture analgesia. ③ NO in NRM joins in the pathological and physiological processes of pain and electroacupuncture analgesia. Its increase can lower the pain threshold greatly.