Westbrook R F, Greeley J D
School of Psychology, University of New South Wales, Sydney, Australia.
Q J Exp Psychol B. 1990 Feb;42(1):1-40.
Eight experiments examined the apparently paradoxical analgesia that accrues when rats are repeatedly injected with an opiate antagonist, naloxone, and exposed to a heat stressor. Experiments 1 and 2 showed that such pairings came to enhance in a dose-dependent manner the latencies with which rats paw-licked in response to the stressor. Experiment 3 demonstrated that the latencies to paw-lick in saline-treated rats decreased with increases in the intensity of the heat, indicating that naloxone had not provoked long latencies to paw-lick by increasing the functional intensity of the stressor. Experiment 4 documented a role for conditioning processes in recruiting the naloxone-induced analgesia. Experiment 5 showed that the analgesic effect was due to the pairings of the drug and the heat stressor, as a history of exposure to naloxone in a distinctive environment did not render the animals analgesic when challenged with the drug and the stressor. Experiments 6 and 7 provided evidence that the conditioned analgesia that accrued from drug-stressor pairings was non-opioid in nature, as the analgesia was observed in morphine-tolerant rats and was not reversed by an administration of naloxone in advance of exposure to the conditioning context. Experiment 8 demonstrated that the administration of morphine in the context previously associated with naloxone-stressor pairings provoked a superanalgesia. Although analgesic on the paw-lick assay, naloxone-treated subjects did not appear to be insensitive to the heat or impaired motorically, as they persistently reared with short latencies. The results were discussed in terms of the collateral inhibition model of the endogenous pain control system, and some speculations were offered concerning the relation between paw-licking and rearing.
八项实验研究了大鼠反复注射阿片类拮抗剂纳洛酮并暴露于热应激源时所产生的明显矛盾的镇痛现象。实验1和实验2表明，这种配对会以剂量依赖的方式延长大鼠对热应激源做出舔爪反应的潜伏期。实验3表明，生理盐水处理的大鼠舔爪潜伏期会随着热强度的增加而缩短，这表明纳洛酮并非通过增加应激源的功能强度来延长舔爪潜伏期。实验4记录了条件作用过程在引发纳洛酮诱导的镇痛中的作用。实验5表明，镇痛作用是由于药物与热应激源的配对，因为在一个独特环境中接触过纳洛酮的经历，在动物受到药物和应激源刺激时并不能使其产生镇痛作用。实验6和实验7提供了证据，表明药物 - 应激源配对产生的条件性镇痛本质上是非阿片类的，因为在吗啡耐受的大鼠中观察到了这种镇痛作用，并且在接触条件刺激环境之前预先给予纳洛酮并不能逆转这种镇痛作用。实验8表明，在先前与纳洛酮 - 应激源配对相关的环境中给予吗啡会引发超镇痛作用。尽管在舔爪试验中纳洛酮处理的大鼠表现出镇痛作用，但它们似乎对热并不不敏感，运动功能也未受损，因为它们会以短潜伏期持续站立。研究结果依据内源性疼痛控制系统的侧支抑制模型进行了讨论，并对舔爪和站立之间的关系提出了一些推测。
