PHYSIOLOGICAL CORRELATES OF NEURAL PLASTICITY

这项研究的长期目标是增加我们对 以下功能恢复和改变的潜在机制 脊髓损伤。人类脊椎下行通路的损伤 已发现脐带会导致过度疼痛的反应 有害的和非有害的刺激，在几个月的时间里形成 受伤后几周。首席调查员假设 这是由于失神经对P物质和/或其他物质超敏所致 速激肽存在于脊髓伤害性神经元中。为了测试这一点 假设，首席调查员将执行以下操作 正常动物和背外侧索动物的实验研究 (DLF)存活时间为1至30天的病变： 1.腰段脊髓神经元对伤害性刺激的反应特性 无毒刺激和谷氨酸脉冲将在 使用和不使用P物质时是否存在分级水平 同时应用5-羟色胺。 2.将使用特定的配体进行类似的实验 对于NK1、NK2和NK3速激肽受体，取代P物质。 3.P物质拮抗剂将长期应用于腰椎 完整动物的脊髓。这些动物将接受测试，以确定 这一过程是否能模仿DFL病变的效果。 4.正常和正常大鼠脊髓神经元的电学特性 将对受损动物进行测量，以确定这些变化 特性可以解释对速激肽的反应增加， 与速激肽受体的变化无关。 5.将使用受体结合放射自显影来测量水平 速激肽和5-羟色胺受体在大鼠脊髓灰质的表达 正常的和有损伤的动物。 前四项研究将涉及细胞外和细胞内。 电生理记录、离子导入和压力 药物在猫身上的应用。最后一项研究将涉及量化 大鼠和猫的受体结合放射自显影分析。 这些研究不仅涉及以下具体问题： 脊髓损伤后的慢性疼痛，也要更一般 中枢和中枢神经后失神经超敏反应的作用问题 周围神经系统损伤。这些结果可能最终导致 治疗脊柱术后顽固性疼痛的新药物疗法 脐带受伤。

The long term goal of this research is to increase our understanding of the mechanisms underlying recovery and alteration of function following spinal cord injury. Damage to descending pathways in the human spinal cord has been found to result in an exaggerated painful response to noxious and non-noxious stimuli, developing over a period of several weeks following injury. The Principal Investigator hypothesizes that this is due to denervation supersensivity to substance P and/or other tachykinins occurring in spinal cord nociceptive neurons. To test this hypothesis, the Principal Investigator will perform the following studies in normal animals and in animals with dorsolateral funiculus (DLF) lesions at survival times of 1 to 30 days: 1. The response properties of lumbar spinal cord neurons to noxious and non-noxious stimuli and to glutamate pulses will be tested in the presence of graded levels of applied substance P, with and without concurrent application of serotonin. 2. Similar experiments will be performed using ligands that are specific for NK1, NK2, and NK3 tachykinin receptors, in place of substance P. 3. A substance P antagonist will be applied chronically to the lumbar spinal cord of intact animals. These animals will be tested to determine if this procedure can mimic the effects of DFL lesions. 4. The electrical properties of spinal cord neurons in normal and lesioned animals will be measured to determine if changes in these properties can account for increased responsiveness to tachykinins, independent of changes in tachykinin receptors. 5. Receptor binding autoradiography will be used to measure the levels of tachykinin and serotonin receptors in the spinal cord grey matter of normal and lesioned animals. The first four studies will involve extracellular and intracellular electrophysiological recording, and iontophoretic and pressure application of drugs in cats. The last study will involve quantitative analysis of receptor binding autoradiography in rats and cats. These studies relate not only to the specific question of the basis for chronic pain after spinal cord injury, but also to the more general question of the role of denervation supersensivity following central and peripheral nervous system injury. These results may ultimately lead to new drug therapies for the treatment of intractable pain after spinal cord injury.