Programme in Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, ON, Canada Faculty of Dentistry, University of Toronto, Toronto, ON, Canada Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.
Pain. 2012 Oct;153(10):2133-2139. doi: 10.1016/j.pain.2012.07.012. Epub 2012 Aug 4.
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 naïve 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.
神经生长因子-3（NT-3）是一种靶源性神经营养因子，可调节感觉神经元的存活和生长。在这里，我们报告说，NT-3 在皮肤感觉神经末梢的发芽中起着关键的许可作用，有助于幼年动物皮肤损伤后的疼痛和敏感性。在新生大鼠和小鼠皮肤损伤后 3-7 天，新生儿皮肤和表皮伤口处的感觉终末发芽伴随着 NT-3 转录物、NT-3 蛋白水平和 NT-3 蛋白释放的增加。用特异性抗体阻断 NT-3 活性可大大减少背根神经节/皮肤共培养物中由受伤皮肤诱导的感觉神经突生长，但不能由未受伤的皮肤诱导。NT-3(+/-)lacZ 杂合转基因小鼠中不存在伤口诱导的过度神经支配，证实了 NT-3 对体内感觉终末发芽的要求。我们的结论是，新生儿皮肤中 NT-3 的上调是介导皮肤损伤后感觉神经发芽的关键因素，这是过敏和疼痛的基础。
