Thomas David A, Anton Fernand, Kenshalo Daniel R, Williams Gene M, Dubner Ronald
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 USA.
Pain. 1993 Oct;55(1):63-70. doi: 10.1016/0304-3959(93)90185-R.
We examined the ability of the alpha 2-adrenoceptor agonist, ST-91, microinjected into the medullary dorsal horn (MDH), to diminish the sensory-discriminative features of noxious heat stimuli in awake behaving monkeys. Two monkeys performed a noxious thermal detection task and the time to detection of small increases in heat served as a measure of the perceived intensity of pain. ST-91 microinjected into the MDH (1.0, 3.0, 10.0 and 30.0 micrograms/0.4 microliter) produced dose-dependent increases in detection time to graded temperature increases (0.4-1.0 degrees C) from a noxious 46 degrees C base line. These dose-dependent effects were attenuated by the systemic administration of the alpha 2-adrenoceptor antagonist, idazoxan (2.0 mg/kg, i.m.), but not by the alpha 1-adrenoceptor antagonist, prazosin (0.5 mg/kg, i.m.) or the opioid-receptor antagonist, naloxone (0.5 mg/kg, i.m.). The effect of ST-91 on detection latency of thermal stimuli was not the result of alterations in attentional, motivational or motoric aspects of the monkeys' behavior, because detection of visual stimuli and non-noxious temperature coolings (36.0-34.5 degrees C) in a similar paradigm were not consistently altered. Microinjection of morphine (3.0 mg) into the MDH also increased detection latency of the noxious heat stimuli. Systemic administration of the opioid-receptor antagonist, naloxone (0.5 mg/kg), and the alpha 2-adrenoceptor antagonist, idazoxan (2.0 mg/kg, i.m.) attenuated these effects of morphine. In a separate experiment, morphine (5.0 micrograms) microinjected into the MDH induced facial scratching behavior. Idazoxan (2.0 mg/kg) was effective at attenuating this scratching behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了向延髓背角(MDH)微量注射α2-肾上腺素能受体激动剂ST-91,对清醒行为猴有害热刺激的感觉辨别特征的影响。两只猴子执行有害热检测任务,检测热小幅升高的时间作为疼痛感知强度的指标。向MDH微量注射ST-91(1.0、3.0、10.0和30.0微克/0.4微升),使从有害的46℃基线开始的分级温度升高(0.4-1.0℃)的检测时间呈剂量依赖性增加。这些剂量依赖性效应被α2-肾上腺素能受体拮抗剂咪唑克生(2.0毫克/千克,肌肉注射)全身给药减弱,但未被α1-肾上腺素能受体拮抗剂哌唑嗪(0.5毫克/千克,肌肉注射)或阿片受体拮抗剂纳洛酮(0.5毫克/千克,肌肉注射)减弱。ST-91对热刺激检测潜伏期的影响不是猴子行为的注意力、动机或运动方面改变的结果,因为在类似范式中视觉刺激和无害温度冷却(36.0-34.5℃)的检测并未持续改变。向MDH微量注射吗啡(3.0毫克)也增加了有害热刺激的检测潜伏期。阿片受体拮抗剂纳洛酮(0.5毫克/千克)和α2-肾上腺素能受体拮抗剂咪唑克生(2.0毫克/千克,肌肉注射)全身给药减弱了吗啡的这些效应。在另一个实验中,向MDH微量注射吗啡(5.0微克)诱发面部抓挠行为。咪唑克生(2.0毫克/千克)有效减弱了这种抓挠行为。(摘要截短于250字)