The narcotic antagonist naloxone enhances clinical pain
The narcotic antagonist naloxone enhances clinical pain
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麻醉拮抗剂纳洛酮可增强临床疼痛
作者：
J. Levine;N. Gordon;R. Jones;H. Fields
内源性阿片样物质（内啡肽）已从多种物种的大脑中分离出来，包括人类1,2。此外，最近有证据表明，大脑拥有一种镇痛系统。内啡肽的分布与中脑导水管周围灰质等中枢神经系统部位一致，在电刺激或微注射阿片激活时产生镇痛作用3 - 5。这就提出了镇痛是由内啡肽释放介导的可能性。目前，关于引发内啡肽释放的因素所知甚少。一个明显的可能性是，疼痛抑制系统是由有害刺激激活的。事实上，据观察，对身体某一部位的有害刺激会降低远处有害刺激的强度。此外，对这一镇痛系统的神经元组成的研究与它被有害刺激激活的观点一致7,8。如果镇痛系统的作用是由内源性吗啡类化合物介导的，那么纳洛酮（一种纯阿片拮抗剂）破坏该系统将会增加持续的有害刺激的感知强度。一些动物研究报告单独使用纳洛酮对基线疼痛阈值没有影响9,10；然而，在其他研究中，在热板和甩尾试验中观察到潜伏期缩短11,12。在人类中，疼痛阈值仅受纳洛酮的影响13,14。然而，电刺激（15,16）或针灸（17）所产生的镇痛逆转已有报道。1965年，Lasagna评论了纳洛酮对术后疼痛患者的“奇怪的超痛觉作用”18。这些观察结果表明，临床疼痛可能为研究内啡肽的作用提供更合适的模型。我们在这里证明，在拔除阻生智齿后，纳洛酮引起的疼痛强度明显高于安慰剂，这一观察结果与内啡肽参与内在疼痛抑制系统的建议一致。
ENDOGENOUS opiate-like substances (endorphins) have been isolated from the brain in a variety of species, including man1,2. Furthermore, there is recent evidence that the brain possesses an analgesia-producing system. The distribution of endorphins is consistent and overlaps significantly with central nervous system sites such as the midbrain periaqueductal grey which produce analgesia when activated by electrical stimulation or opiate microinjection3–5. This raises the possibility that the analgesia is mediated by endorphin release. At present very little is known about the factors which trigger endorphin release. One obvious possibility is that the pain suppression system is activated by noxious stimuli. In fact, it has been observed that noxious stimuli delivered at one region of the body reduce the reported intensity of a distant noxious stimulus6. Furthermore, studies of the component neurones of this analgesia-producing system are consistent with the idea that it is activated by noxious stimuli7,8. If the action of the analgesia-producing system is mediated by endogenous morphine-like compounds, then disruption of this system by naloxone, a pure opiate antogonist, would be expected, to increase the perceived intensity of a maintained noxious stimulus. Some animal studies report no effect of naloxone alone on baseline pain thresholds9,10; in other studies, however, a shortening of latencies on hot-plate and tail-flick tests has been observed11,12. In humans, pain thresholds are unaffected by naloxone alone13,14. However, reversal of analgesia produced by electrical stimulation15,16 or by acupuncture17 has been reported. In 1965 Lasagna commented on the “curious hyper-algesic effect” of naloxone in patients with postoperative pain18. These observations suggested that clinical pain might provide a more appropriate model to study the action of endorphins. We demonstrate here that following the extraction of impacted wisdom teeth, naloxone causes a significantly greater increase in reported pain intensity than placebo, an observation consistent with the suggested participation of endorphins in an intrinsic pain suppression system.