A role for NT-3 in the hyperinnervation of neonatally wounded skin
A role for NT-3 in the hyperinnervation of neonatally wounded skin
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DOI：
10.1016/j.pain.2012.07.012
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发表时间：
2012-10-01
期刊：
影响因子：
7.4
通讯作者：
Fitzgerald, Maria
中科院分区：
文献类型：
--
作者：
Beggs, Simon;Alvares, Debie;Fitzgerald, Maria
神经营养因子-3 （NT-3）是一种调节感觉神经元存活和生长的靶源性神经营养因子。在这里，我们报道NT-3在皮肤感觉神经发芽中起关键的允许作用，这有助于年幼动物皮肤损伤后的疼痛和敏感性。新生大鼠和小鼠皮肤损伤后3-7天，新生真皮和表皮的感觉末端萌发伴随着NT-3转录、NT-3蛋白水平和NT-3蛋白释放的增加。在背根神经节/皮肤共培养中，用特异性抗体对NT-3活性进行功能性阻断，可大大减少损伤皮肤诱导的感觉神经突生长，而非单纯皮肤诱导的感觉神经突生长。在杂合转基因小鼠（NT-3(+/) lacZ）中，没有创伤诱导的高神经支配，证实了NT-3对体内感觉末端发芽的需求。我们得出结论，NT-3在新生儿损伤皮肤中的上调是介导感觉神经发芽的关键因素，而感觉神经发芽是皮肤损伤后过敏和疼痛的基础。(C) 2012年国际疼痛研究协会。Elsevier B.V.版权所有。
Neurotrophin-3 (NT-3) is a target-derived neurotrophic factor that regulates sensory neuronal survival and growth. Here we report that NT-3 plays a critical permissive role in cutaneous sensory nerve sprouting that contributes to pain and sensitivity following skin wounding in young animals. Sensory terminal sprouting in neonatally wounded dermis and epidermis is accompanied by increased NT-3 transcription, NT-3 protein levels, and NT-3 protein release 3-7 days post skin injury in newborn rats and mice. Functional blockade of NT-3 activity with specific antibodies greatly reduces sensory neurite outgrowth induced by wounded skin, but not by naive skin, in dorsal root ganglion/skin co-cultures. The requirement for NT-3 for sensory terminal sprouting in vivo is confirmed by the absence of wound-induced hyperinnervation in heterozygous transgenic mice (NT-3(+/) lacZ). We conclude that upregulation of NT-3 in neonatally wounded skin is a critical factor mediating the sensory nerve sprouting that underlies hypersensitivity and pain following skin injury. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.