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脊髓损伤大鼠中静脉注射μ阿片类和κ阿片类药物对伤害性反射和非伤害性反射的选择性

On the selectivity of intravenous mu- and kappa-opioids between nociceptive and non-nociceptive reflexes in the spinalized rat.

作者信息

Parsons C G, Headley P M

机构信息

Department of Physiology, School of Medical Sciences, University of Bristol.

出版信息

Br J Pharmacol. 1989 Oct;98(2):544-51. doi: 10.1111/j.1476-5381.1989.tb12628.x.

Abstract
  1. In electrophysiological experiments in spinalized, alpha-chloralose anaesthetized rats, opioids and anaesthetics were tested intravenously (i.v.) on the responses of individual motoneurones to alternating noxious (heat or pinch) and non-noxious (tap or vibration) stimuli. 2. On cells that were sensitive to low doses of mu-opioids, both fentanyl (0.5-4 micrograms kg-1 i.v.) and morphine (0.5 mg kg-1 i.v.) selectivity reduced reflexes to noxious stimuli to a greater degree than the higher doses required to reduce nociceptive reflexes (fentanyl 8 micrograms kg-1 i.v.; morphine 1-8 mg kg-1 i.v.) depressed non-nociceptive reflexes to a similar degree. 3. A similar spectrum of selectivity was seen with U-50,488 (0.5-16 mg kg-1 i.v.) although statistically significant selective depression of reflexes was only evident at the lowest dose tested (0.5 mg kg-1 i.v.). All effects of U-50,488 were readily reversed by low doses of the opioid antagonist, naloxone (10-100 micrograms kg-1 i.v.). 4. The dissociative anaesthetic/PCP ligand ketamine (0.5-4 mg kg-1 i.v.) was similar in having selective actions at low doses on sensitive cells but non-selective actions when higher doses were required. In contrast, the general anaesthetics methohexitone (4 mg kg-1 i.v.) and alphadolone/alphaxalone (1 mg kg-1 i.v.) were consistently non-selective between reflexes to noxious and non-noxious stimuli. alpha-Chloralose (20-40 mg kg-1 i.v.) had very little effect on reflexes to any of the synaptic inputs tested.
摘要
  1. 在脊髓麻醉、α-氯醛糖麻醉的大鼠进行的电生理实验中,静脉注射(i.v.)阿片类药物和麻醉剂,测试单个运动神经元对交替的有害(热或捏)和无害(轻拍或振动)刺激的反应。2. 在对低剂量μ-阿片类药物敏感的细胞上,芬太尼(0.5 - 4微克/千克静脉注射)和吗啡(0.5毫克/千克静脉注射)对有害刺激反射的选择性降低程度大于降低伤害性反射所需的较高剂量(芬太尼8微克/千克静脉注射;吗啡1 - 8毫克/千克静脉注射)对非伤害性反射的抑制程度。3. U - 50,488(0.5 - 16毫克/千克静脉注射)也有类似的选择性谱,尽管仅在测试的最低剂量(0.5毫克/千克静脉注射)时,反射的统计学显著选择性抑制才明显。U - 50,488的所有作用都可被低剂量的阿片类拮抗剂纳洛酮(10 - 100微克/千克静脉注射)轻易逆转。4. 解离性麻醉剂/苯环己哌啶配体氯胺酮(0.5 - 4毫克/千克静脉注射)在低剂量时对敏感细胞有选择性作用,但在需要较高剂量时则无选择性作用。相比之下,全身麻醉剂美索比妥(4毫克/千克静脉注射)和阿法多龙/阿法沙龙(1毫克/千克静脉注射)对有害和无害刺激的反射始终无选择性。α-氯醛糖(20 - 40毫克/千克静脉注射)对所测试的任何突触输入的反射影响很小。

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