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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene
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Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene

机译：CGRP基因的差异表达介导了对有害热量的可变敏感性

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摘要

Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli. We further present convergent behavioral and electrophysiological evidence that the variable responses to noxious heat are due to strain-dependence of CGRP expression and sensitivity. Strain differences in behavioral response to noxious heat could be abolished by peripheral injection of CGRP, blockade of cutaneous and spinal CGRP receptors, or long-term inactivation of CGRP with a CGRP-binding Spiegelmer. Linkage mapping supports the contention that the genetic variant determining variable heat pain sensitivity across mouse strains affects the expression of the Calca, gene that codes for CGRP alpha.
机译：热敏性在人和实验动物中显示出相当大的功能可变性，并且是炎症性疼痛和可能的神经性疼痛的基础。至少在小鼠中，大多数这种变异是遗传的，因为近交品系对有害热量的行为敏感性差异很大。此处显示的这些应变差异反映了主要传入热伤害感受器对热刺激的不同响应。我们进一步提供了收敛的行为和电生理证据，表明对有害热量的可变反应是由于CGRP表达和敏感性的应变依赖性所致。可通过外周注射CGRP，阻断皮肤和脊髓CGRP受体或通过与CGRP结合的Spiegelmer长期灭活CGRP来消除对有害热量的行为反应中的菌株差异。连锁作图支持这样的论点，即确定跨小鼠品系的可变热痛敏感性的遗传变异会影响Calca（表达CGRPα的基因）的表达。

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