SPINAL CORD PLASTICITY MODEL USING NERVE GROWTH FACTOR

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 电生理学、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NGF，而剥夺NGF 结果使这些传入物质转化为低阈值机械感受器； B)这种转换导致这些脊椎投影的改变 C)在接受NGF治疗的成人中观察到的行为痛敏 脊柱投射系统改变的结果，特别是 涉及某些氨基酸(NMDA)受体；以及d)神经再支配 成人的伤害性感受器需要神经生长因子。实验设计包括检查 神经生长因子及其抗体对感觉神经元的影响 生理上或解剖学上)，对已鉴定的脊髓神经元和 电路，以及对自然和电的某些行为反应 刺激。用NGF或抗NGF治疗的动物将分别与 其他和年龄匹配的未经处理的对照组。与健康相关的 这些实验的意义源于有必要进一步 有关成人神经系统能力的基本信息 在受伤后修改其连通性，并记录 自然产生的生物制剂，如NGF来调节这一点 可塑性。此外，NGF也是促进神经再生的候选因子。 损伤后的某些神经元类型，有必要确定其 在体对哺乳动物脊髓的功能影响。

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 behavioural methods to investigate various aspects of this plasticity in rats. Several hypotheses will be investigated, including a) the possibility that nociceptive afferents require NGF in a postnatal critical period and that deprivation from NGF results in conversion of these afferents to low threshold mechanoreceptor; b) that such conversion results in changes in spinal projection of these afferents; c) that behavioural 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 NGF. 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 behavioural 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.