Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.
Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.
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疼痛敏感性和加压素镇痛是通过基因性 - 性 - 环境相互作用介导的。
DOI：
10.1038/nn.2941
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发表时间：
2011-10-23
影响因子：
25
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中科院分区：
文献类型：
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小鼠化学性/炎症性疼痛的定量性状基因座定位确定了Avpr 1a基因，编码血管加压素-1A受体（V1 AR），负责福尔马林和辣椒素的应变依赖性疼痛敏感性。一项人类遗传关联研究揭示了AVPR 1A内的单核苷酸多态性（rs 10877969）对辣椒素疼痛水平的影响，但仅限于在测试时报告压力的男性受试者。血管加压素类似物去氨加压素的镇痛功效揭示了药物和急性应激之间的类似相互作用，因为去氨加压素对辣椒素疼痛的抑制仅见于非应激受试者。在小鼠中的其他实验证实了V1 AR和应激的男性特异性相互作用，从而得出结论，加压素激活内源性镇痛机制，除非它们已经被应激激活。这些研究结果代表了第一个明确的证明镇痛效果取决于接受者的情绪状态，并说明了启发式的板凳到床边到板凳的翻译策略的力量。
Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, encoding the vasopressin-1A receptor (V1AR), as responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) within AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog, desmopressin, revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was seen only in non-stressed subjects. Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.