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首页> 外文期刊>Life sciences >Lack of tolerance in peripheral opioid analgesia in mice.
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Lack of tolerance in peripheral opioid analgesia in mice.

机译：小鼠外周阿片类镇痛耐受性不足。

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摘要

We recently developed a sensitive peripheral analgesic test in mice. Bradykinin, a representative pain-producing substance, when given subcutaneously through a polyethylene tube into the plantar of the limb connected to a transducer, induced a flexor reflex response, in a dose dependent manner. When morphine, a mu-opioid receptor agonist, was added to the plantar through another polyethylene tube, bradykinin-induced responses were completely abolished in a naloxone-reversible manner. These peripheral analgesic effects were also observed with DAMGO, another mu-opioid receptor agonist, and U-69,593, a kappa-opioid receptor agonist, but not DSLET, a delta-opioid receptor agonist. When morphine was given subcutaneously to the back, a potent analgesia in the tail pinch test was observed. Repeated administrations of morphine once per day for 5 days showed a marked tolerance or reduction in morphine analgesia on the 6th day, while there was no significant reduction in the peripheral analgesia of morphine. These findings suggest that tolerance to morphine analgesia is mediated through synaptic plasticity in the central nervous system, but not through a receptor desensitization at the level of the single cell.
机译：我们最近在小鼠中开发了一种敏感的外周镇痛试验。缓激肽是一种典型的疼痛产生物质，当通过聚乙烯管皮下注射到与换能器相连的四肢的足底时，会以剂量依赖性方式引起屈肌反射反应。当吗啡（一种μ阿片类受体激动剂）通过另一个聚乙烯管加入足底时，缓激肽诱导的反应以纳洛酮可逆的方式被完全消除。这些外周镇痛作用还可以通过另一种阿片类阿片受体激动剂DAMGO和K-类阿片受体激动剂U-69,593来观察到，而δ-阿片类受体激动剂DSLET则没有。当吗啡皮下注射到背部时，在尾巴捏试验中观察到有效的镇痛作用。每天重复给药5天一次的吗啡，在第6天显示出明显的耐受性或吗啡镇痛作用降低，而吗啡的外周镇痛没有明显降低。这些发现表明，对吗啡镇痛的耐受性是通过中枢神经系统中突触可塑性介导的，而不是通过单细胞水平的受体脱敏来介导的。

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