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背景:镇痛是野罂粟主要功效之一。以往的研究证明其具有显著镇痛作用的主要有效部位为总生物碱。野罂粟碱是从其总生物碱中分离出来的一种新的生物碱。目的:探讨野罂粟碱的镇痛作用及其作用机制。设计:以实验动物为观察对象的随机对照实验。单位:承德医学院中药研究所材料:实验于2001-08/2003-12在承德医学院中药研究所(河北省中药研究与开发重点实验室)完成。选用140只小鼠,随机分为14组,每组10只。方法:①镇痛效果比较。随机分5组:盐水对照组,罂粟碱2.5,5.0和10.0mg/kg组和吗啡组。②与内啡肽关系比较。随机分5组:盐水对照组,野罂粟碱组,野罂粟碱+纳洛酮组,吗啡组和吗啡+纳洛酮组。③与一氧化氮关系比较。随机分4组,盐水对照组,野罂粟碱组,野罂粟碱+L-精氨酸400m g/kg组和L-硝基精氨酸甲酯37.5mg/kg组。致痛方法为小鼠右后足掌皮下注射10g/L 甲醛20μL,疼痛观察项目为行走自如得0分;跛行,不动时撑地得1分;抬足得2分;抖足或舔足得3分。观察分两个时相:致痛后0～10m in 为第1时相,20～30m in 为第2时相。主要观察指标:不同药物作用下各组小鼠的疼痛反应评分。结果:①野罂粟碱可显著的降低甲醛致痛小鼠第2时相的疼痛反应评分(P <0.05～0.01)。大剂量对第1时相的疼痛反应也有一定的抑制作用(P <0.05)。吗啡对两个时相的疼痛反应均有显著的抑制作用(P <0.01)。②纳洛酮可完全拮抗吗啡的镇痛作用,而对野罂粟碱的镇痛作用无明显影响。③L-精氨酸可减弱野罂粟碱对第2相疼痛反应的抑制作用,L-硝基精氨酸甲酯可增强野罂粟碱的镇痛作用。结论:野罂粟碱有显著的镇痛作用,阿片拮抗剂纳络酮可完全拮抗吗啡的镇痛作用,但不能改变野罂粟碱的作用,提示野罂粟碱的镇痛作用与内源性阿片系统无关。L-精氨酸可部分的抑制野罂粟碱的镇痛作用,而L-硝基精氨酸甲酯对野罂粟碱的镇痛作用有一定的增强作用。提示野罂粟碱的镇痛可能部分的与抑制一氧化氮的生成或释放有关。
Background: Analgesia is one of the main effects of wild poppy. Previous studies have demonstrated that the main effective site for significant analgesia is total alkaloids. Papaverine is a new alkaloid that is isolated from its total alkaloids. Objective: To investigate the analgesic effect of Papaverine and its mechanism of action. Design: A randomized controlled trial using experimental animals as the subject of observation. Unit: Institute of Traditional Chinese Medicine, Chengde Medical College Material: The experiment was completed at the Institute of Traditional Chinese Medicine, Chengde Medical College (Key Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province) from August 2001 to December 2003. 140 mice were randomly divided into 14 groups of 10 in each group. Methods: 1 Comparison of analgesic effects. Randomly divided into 5 groups: saline control group, papaverine 2.5, 5.0 and 10.0mg/kg group and morphine group. 2 Comparison with endorphins. Randomly divided into 5 groups: saline control group, papaverine group, papaverine + naloxone group, morphine group and morphine + naloxone group. 3 Comparison with nitric oxide. Randomly divided into 4 groups, saline control group, papaverine group, wild papaverine + L-arginine 400mg/kg group and L-nitroarginine methyl ester 37.5mg/kg group. The method of causing pain was subcutaneous injection of 10 g/L formaldehyde 20 μL into the right hind paw of the mouse. The pain observation item was 0 with ease when walking; the limp, 1 point when the animal was immobilized; and the foot was 2 points; Get 3 points. Observed in two phases: after the onset of pain 0 ~ 10m in the first phase, 20 ~ 30m in the second phase. MAIN OUTCOME MEASURES: Pain response scores of mice in each group under different drugs. RESULTS: 1Papaveropine significantly reduced the pain response score of the second phase of formaldehyde induced mice (P <0.05-0.01). Large doses also had a certain inhibitory effect on the pain response at the first phase (P < 0.05). Morphine had a significant inhibitory effect on the pain responses of both phases (P < 0.01). 2Naloxone can completely antagonize the analgesic effect of morphine, but has no significant effect on the analgesic effect of Papaverine. 3L-arginine can attenuate the inhibitory effect of Papaverine on the pain response of the second phase. L-nitroarginine methyl ester can enhance the analgesic effect of Papaverine. Conclusion: Papaverine has a significant analgesic effect. The opioid antagonist naloxone can completely antagonize the analgesic effect of morphine, but it can not change the effect of Papaverine, suggesting that the analgesic effect of Papaverine and endogenous opioid system Nothing to do. L-Arginine can partially inhibit the analgesic effect of Papaverine, and L-nitro-L-Arginine methyl ester can enhance the analgesic effect of Papaverine. It is suggested that the analgesic effect of Papaverine may be partly related to the inhibition of the production or release of nitric oxide.