Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin
Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin
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DOI：
10.1038/383535a0
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发表时间：
1996-10-10
期刊：
影响因子：
64.8
通讯作者：
Zimmer, A
中科院分区：
文献类型：
--
作者：
Konig, M;Zimmer, AM;Zimmer, A
脑啡肽是一种内源性阿片肽，来源于前脑啡肽前体蛋白(1，2)。它们被认为在调节许多生理功能方面至关重要，包括痛觉和止痛、对压力、攻击和支配的反应(3-5)。在这里，我们使用遗传学方法来研究哺乳动物阿片系统的作用。我们在胚胎干细胞中通过同源重组破坏了前脑啡肽原基因，从而产生了脑啡肽缺乏的小鼠。突变的Enk(-/-)动物健康、多产并照顾后代，但表现出显著的行为异常。携带Enk(-/-)基因的小鼠更焦虑，雄性表现出更强的攻击性。突变动物在脊柱上对疼痛刺激的反应上与对照组有显著差异，但在脊柱上没有明显差异。出乎意料的是，Enk(-/-)小鼠表现出正常的应激诱导镇痛作用。我们的结果表明，脑啡肽调节对疼痛刺激的反应。因此，遗传因素可能对疼痛的体验有很大影响。
ENKEPHALINS are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein(1,2). They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance (3-5). Here we have used a genetic approach to study the role of the mammalian opioid system. We disrupted the preproenkephalin gene using homologous recombination in embryonic stem cells to generate enkephalin-deficient mice. Mutant enk(-/-) animals are healthy, fertile, and care for their offspring, but display significant behavioural abnormalities. Mice with the enk(-/-) genotype are more anxious and males display increased offensive aggressiveness. Mutant animals show marked differences from controls in supraspinal, but not in spinal, responses to painful stimuli. Unexpectedly, enk(-/-) mice exhibit normal stress-induced analgesia. Our results show that enkephalins modulate responses to painful stimuli. Thus, genetic factors may contribute significantly to the experience of pain.