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脊髓可塑性。 这种神经营养素似乎 选择性地作用于伤害性传入神经， 对皮肤造成伤害的信号。 这些实验将利用 电生理学、解剖学和行为学方法来研究 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， 需要NCF在出生后的关键时期， 导致这些传入神经转换为低阈值 B）这种转换导致脊髓神经元的变化， 这些传入神经的投射; c）在 接受神经生长因子治疗的成人是由于脊柱投射系统的变化， 特别是涉及某些氨基酸（NMDA）受体的那些;和d） 成人伤害感受器的神经再支配需要NCF。 实验 设计涉及检查神经生长因子及其抗体对感觉的影响， 神经元（在生理学或解剖学上识别），在识别的脊髓 神经元和电路，以及对自然和 电刺激 用NGF或抗NGF处理的动物将被 并与年龄匹配的未治疗对照组进行比较。 健康- 这些实验的相关意义来自于需要有 关于成人神经系统能力的进一步基本信息 系统在受伤后修改其连接性，并记录 天然存在的生物制剂如NGF调节 这种可塑性。此外，NGF是促进再生的候选者 损伤后的某些神经元类型，有必要确定 其在体内对哺乳动物脊髓的功能作用。

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.