NERVE GROWTH FACTOR AND PAIN

本研究的长期目标是开发一种脊柱模型。 使用神经生长因子的脐带可塑性。这种神经营养因子似乎 选择性作用于负责伤害性传入的 表明皮肤受损。这些实验将利用 电生理、解剖学和行为学方法研究 老鼠体内这种可塑性的各个方面。几个假设将是 调查，包括a)伤害性传入的可能性 在出生后关键期需要NCF和剥夺NGF 导致这些传入信号转换为低阈值 机械感受器；b)这种转换导致脊髓的变化 这些传入的投射；c)观察到行为痛敏 NGF治疗的成人是由于脊柱投射系统的变化， 尤其是涉及某些氨基酸(NMDA)受体的那些；和d) 成人伤害性感受器的再支配需要NCF。实验 设计包括检查神经生长因子及其抗体对感觉的影响 神经元(生理学或解剖学鉴定)，在鉴定的脊髓上 神经元和电路，以及对自然和 电刺激。用NGF或抗NGF治疗的动物将被 相互比较，并与年龄匹配的未经治疗的对照组进行比较。健康- 这些实验的相关意义源于需要 有关成人神经质能力的更多基本信息 系统在受伤后修改其连接性，并记录 神经生长因子等天然生物制剂的调节能力 这种可塑性。此外，NGF也是促进再生的候选因子。 损伤后某些神经元类型的变化，有必要确定 其对哺乳动物体内脊髓的功能影响。

The long term objective of this research is to develop a model of spinal cord plasticity using nerve growth factor. This neuronotrophin appears to act selectively on nociceptive afferents that are responsible for signalling damage to the skin. The experiments will make use of electrophysiological, anatomical and behavioral methods to investigate various aspects of this plasticity in rats. Several hypotheses will be investigated, including a) the possibility that nociceptive afferents require NCF in a postnatal critical period and that deprivation from NGF results in conversion of these afferents to low threshold mechanoreceptors; b) that such conversion results in changes in spinal projection of these afferents; c) that behavioral hyperalgesia observed in NGF-treated adults results from changes in spinal projection systems, particularly those involving certain amino acid (NMDA) receptors; and d) that reinnervation of nociceptors in adults requires NCF. Experimental design involves examining the effects of NGF and its antibody on sensory neurons (identified physiologically or anatomically), on identified spinal neurons and circuits, and on certain behavioral responses to natural and electrical stimulation. Animals treated with NGF or anti-NGF will be compared to each other and to age-matched untreated controls. The health- related significance of these experiments derives from the need to have further basic information concerning the capacity of the adult nervous system to modify its connectivity after injury, and to document the ability of naturally-occurring biological agents such as NGF to regulate this plasticity. Furthermore, NGF is a candidate to promote regeneration of certain neuronal types after injury, and it is necessary to ascertain its functional effects on the mammalian spinal cord in vivo.