Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation.
Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation.
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DOI：
10.1097/j.pain.0000000000000770
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发表时间：
2017-02
期刊：
影响因子：
7.4
通讯作者：
Jankowski MP
中科院分区：
文献类型：
--
作者：
Liu X;Green KJ;Ford ZK;Queme LF;Lu P;Ross JL;Lee FB;Shank AT;Hudgins RC;Jankowski MP
皮肤炎症改变了受影响的背根神经节（DRG）中初级传入神经的功能和基因表达。然而，发育过程中损伤诱导的外周传入敏化和行为超敏反应的具体机制尚未完全了解。最近在儿童中的研究表明生长激素（GH）在疼痛调节中的潜在作用。生长激素调节损伤后的体内平衡和组织修复，但生长激素如何影响新生儿的伤害感受尚不清楚。为了确定生长激素是否在年轻小鼠皮肤炎症过程中调节感觉神经元功能和高反应性中发挥作用，我们使用离体毛状皮肤隐神经背根神经节（DRG）-脊髓制备检查了行为超敏反应和皮肤传入的反应特性。结果表明，在出生后第7天（P7）或P14开始的多毛后爪皮肤炎症降低了受影响皮肤中的GH水平。此外，用外源性GH预处理发炎小鼠，除了改变伤害感受器功能外，还可逆转机械和热超敏反应。这些作用可能是通过上调胰岛素样生长因子1受体（IGFr 1）介导的，因为GH在体外和体内调节DRG神经元中IGFr 1的转录输出。在炎症过程中IGFr 1的传入选择性敲低也防止了观察到的损伤诱导的皮肤传入和行为超敏反应的改变，类似于GH预处理后。这些结果表明，生长激素可以阻断炎症诱导的伤害性感受器敏感性在出生后的发展，导致减少疼痛样行为，可能通过抑制上调IGFr 1的背根神经节。
Cutaneous inflammation alters the function of primary afferents and gene expression in the affected dorsal root ganglia (DRGs). However specific mechanisms of injury-induced peripheral afferent sensitization and behavioral hypersensitivity during development are not fully understood. Recent studies in children suggest a potential role for growth hormone (GH) in pain modulation. GH modulates homeostasis and tissue repair after injury, but how GH effects nociception in neonates is not known. To determine if GH played a role in modulating sensory neuron function and hyper-responsiveness during skin inflammation in young mice, we examined behavioral hypersensitivity and the response properties of cutaneous afferents using an ex vivo hairy skin-saphenous nerve-dorsal root ganglion (DRG)-spinal cord preparation. Results show that inflammation of the hairy hindpaw skin initiated at either postnatal day 7 (P7) or P14 reduced GH levels specifically in the affected skin. Furthermore, pretreatment of inflamed mice with exogenous GH reversed mechanical and thermal hypersensitivity in addition to altering nociceptor function. These effects may be mediated via an upregulation of insulin-like growth factor 1 receptor (IGFr1) as GH modulated the transcriptional output of IGFr1 in DRG neurons in vitro and in vivo. Afferent-selective knockdown of IGFr1 during inflammation also prevented the observed injury-induced alterations in cutaneous afferents and behavioral hypersensitivity similar to that following GH pretreatment. These results suggest that GH can block inflammation-induced nociceptor sensitization during postnatal development leading to reduced pain-like behaviors, possibly by suppressing the upregulation of IGFr1 within DRGs.