DORSAL HORN/THALAMIC CIRCUITRY

背角/丘脑回路

• 批准号: 6243557
• 负责人: HENRY J RALSTON
• 金额: $ 15.99万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243557
• 关键词: GABA receptor; Macaca fascicularis; afferent nerve; analgesia; brain mapping; central neural pathway /tract; dorsal horn; electrophysiology; gamma aminobutyrate; hyperalgesia; immunocytochemistry; laboratory rat; microscopy; neural degeneration; neural information processing; neural inhibition; neural transmission; neuronal transport; pain; sciatic nerve; spinal cord mapping; stimulus /response; thalamus

Project 4 of this Program Project is concerned with changes in the central nervous system that follow peripheral nerve injury. We will use an experimental mononeuropathy model in rat, and subsequently in monkey, which leads to pain behavior in the animals characterized by abnormal posture of the affected limb and exaggerated responses to innocuous stimuli (allodynia) as well as to noxious stimuli (hyperalgesia). Several investigators have shown that partial ligation of the sciatic nerve of the rat leads to degeneration of substantial populations of myelinated and of nonmyelinated axons in the nerve. In a pilot study we have shown that at 14 days postligature there is extensive axonal and synaptic degeneration in the dorsal horn of the rat spinal cord, during a period in which the animal exhibits pain behavior. Other studies have suggested that there is impaired inhibitory circuitry in the dorsal horn of such animals. We will use axon transport combined with immunocytochemical, electron microscopic techniques to examine the circuitry of the dorsal horn at various times following peripheral nerve injury as the pain-related behavior is first manifested until it gradually wanes over a two-month period. Our working hypothesis is that pain behavior can be correlated with changes in the dorsal horn, particularly in the GABAergic circuitry at various survival times. The second major aspect of the study is an examination of the projections of spinothalamic tract ells in the affected segments to the thalamus, the working hypothesis being that there are changes in circuitry in the thalamus that can be correlated with changes in pair behavior, particularly in the monkey. We have previously shown that there is a distinct difference between systems that convey pair information, as well as systems that convey information about innocuous stimuli, in the primate thalamus. We suggest that the thalamic circuitry receiving input from affected spinal segments will be modified as a consequence of the peripheral nerve injury. In humans, pain is often a consequence of peripheral nerve injury and out studies proposed here may lead to a design of rational therapies based upon an understanding of alterations in neural circuitry of the spinal cord and thalamus after peripheral nerve injury. In particular, we hypothesize that the inhibitory circuitry of the cord and thalamus is subject to changes following nerve injury and as we better understand the reorganization of the nervous system that takes place following peripheral nerve injury, improved pharmacological therapies designed to address these changes may ultimately be developed.

本项目的第四个项目涉及的是 周围神经损伤后中枢神经系统损害。 我们将使用 在大鼠中，随后在猴中， 导致动物的疼痛行为， 患肢的姿势和对无害物质的过度反应 刺激（异常性疼痛）以及伤害性刺激（痛觉过敏）。 一些研究者已经证明，部分结扎坐骨神经 大鼠的神经导致大量的 神经中有髓和无髓轴突。 在试点研究中， 已经表明，在结扎后14天，有广泛的轴突， 大鼠脊髓背角突触变性， 动物表现出疼痛行为的时期。 其他研究 表明脊髓背角的抑制回路受损 这样的动物。 我们将使用轴突运输结合 免疫细胞化学，电子显微镜技术，以检查 背角的电路在不同的时间后，周围神经 伤害作为疼痛相关的行为首先表现出来，直到它 在两个月内逐渐减弱。 我们的假设是 疼痛行为可以与背角的变化相关， 特别是在不同存活时间的GABA能回路中。 的 这项研究的第二个主要方面是审查预测， 脊髓丘脑束细胞在受影响的节段到丘脑， 工作假设是，有变化的电路中， 丘脑与配对行为的变化有关， 尤其是在猴子身上。 我们以前已经证明，有一个 传递配对信息的系统之间也有明显的区别， 作为传达无害刺激信息的系统， 灵长类丘脑 我们认为接受输入的丘脑回路 受影响的脊柱节段将被修改， 周围神经损伤 在人类中，疼痛通常是外周神经损伤和 这里提出的研究可能会导致合理的治疗设计， 在理解脊髓神经回路的改变后， 周围神经损伤后的脊髓和丘脑。 我们尤其 假设脊髓和丘脑的抑制回路 神经损伤后的变化，随着我们更好地了解 神经系统的重组发生在 周围神经损伤，改进的药理学治疗， 这些变化最终可能会得到发展。