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吗啡及多种阿片类激动剂对单神经病大鼠热觉过敏和痛觉过敏的不同作用

Differential action of morphine and various opioid agonists on thermal allodynia and hyperalgesia in mononeuropathic rats.

作者信息

Lee S H, Kayser V, Desmeules J, Guilbaud G

机构信息

Unité de Recherches de Physiopharmacologie du Système Nerveux, Inserm U 161, 2 rue d'Alesia, 75014, ParisFrance.

出版信息

Pain. 1994 May;57(2):233-240. doi: 10.1016/0304-3959(94)90228-3.

Abstract

In a rat model of mononeuropathy produced by 4 loose ligatures around the common sciatic nerve, the effects of 1 mg/kg morphine and mu-, delta- and kappa-agonists, DAMGO (2 and 3 mg/kg), BUBUC (3 and 6 mg/kg) and U-69,593 (1.5 mg/kg), were evaluated by measuring the struggle latency (SL in sec) to immersion of the paw on the nerve-injured side in a cold (10 degrees C) or hot (42 degrees C, 44 degrees C, and 46 degrees C) water bath. Experiments were performed 2 weeks after surgery. The agonists were used at doses that produced potent antinociceptive effects on the vocalization test in this model. At 46 degrees C (clearly in the noxious range), only morphine and DAMGO had significant effects. The effect of morphine lasted for more than 2 h with a maximum at 40 min (SL = 13.8 +/- 1.6 sec, 252% of control values). For 2 and 3 mg/kg DAMGO, the dose-related effect lasted for 120 min at least, with a maximum at 20-40 min (SL = 6.0 +/- 0.5 and 8.8 +/- 0.7 sec, 148% and 170% of control values, respectively). These effects were more potent and prolonged than in normal rats and were reversed by 0.1 mg/kg naloxone i.v. By contrast, morphine and all selective agonists failed to relieve the abnormal reactions to 10 degrees C, 42 degrees C (in the non-noxious range) and 44 degrees C (at the noxious threshold) stimuli. Our data illustrate a differential effect of opioids on nociceptive tests based on different stimulus modalities and intensities in this model of mononeuropathic pain.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在通过对坐骨神经进行4次松结扎制作的单神经病变大鼠模型中,通过测量将神经损伤侧爪子浸入冷(10℃)或热(42℃、44℃和46℃)水浴中的挣扎潜伏期(以秒为单位的SL),评估了1mg/kg吗啡以及μ、δ和κ激动剂DAMGO(2mg/kg和3mg/kg)、BUBUC(3mg/kg和6mg/kg)和U-69,593(1.5mg/kg)的作用。实验在手术后2周进行。这些激动剂的使用剂量在该模型的发声测试中产生了有效的镇痛作用。在46℃(明显处于有害范围)时,只有吗啡和DAMGO有显著作用。吗啡的作用持续超过2小时,在40分钟时达到最大值(SL = 13.8±1.6秒,为对照值的252%)。对于2mg/kg和3mg/kg的DAMGO,剂量相关作用至少持续120分钟,在20 - 40分钟时达到最大值(SL分别为6.0±0.5秒和8.8±0.7秒,分别为对照值的148%和170%)。这些作用比正常大鼠更强且更持久,并可被0.1mg/kg静脉注射的纳洛酮逆转。相比之下,吗啡和所有选择性激动剂均未能缓解对10℃、42℃(在非有害范围)和44℃(在有害阈值)刺激的异常反应。我们的数据表明,在该单神经病变性疼痛模型中,阿片类药物对基于不同刺激方式和强度的伤害性测试有不同作用。(摘要截断于250字)

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