DORSAL HORN/THALAMIC CIRCUITRY

背角/丘脑回路

• 批准号: 6112220
• 负责人: HENRY J RALSTON
• 金额: $ 16.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112220
• 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.

该计划项目的项目4涉及变化 遵循周围神经损伤的中枢神经系统。 我们将使用 大鼠的实验单肌病模型，随后在猴子中， 这导致以异常为特征的动物疼痛行为 受影响的肢体的姿势和对无害的反应 刺激（异常性）以及有害刺激（痛苦）。 一些调查人员表明，坐骨神经的部分结扎 大鼠的神经导致大量种群的变性 神经中的髓鞘和非乳腺轴突。 在一项试点研究中，我们 已经表明，在婚姻后14天有广泛的轴突和 大鼠脊髓背角的突触变性，期间 动物表现出疼痛行为的时期。 其他研究也有 建议在背喇叭中有抑制作用受损 这样的动物。 我们将使用轴突运输与 免疫细胞化学，电子显微镜技术检查 外周神经后不同时间的背角电路 受伤，因为与疼痛相关的行为首先表现为 在两个月的时间内逐渐减弱。 我们工作的假设是 疼痛行为可以与背喇叭的变化相关， 特别是在各种生存时间的GABA能电路中。 这 该研究的第二个主要方面是对预测的检查 丘脑的脊柱丘脑段Ells在丘脑的受影响段， 工作假设是电路中有变化 丘脑可以与成对行为的变化相关， 特别是在猴子中。 我们以前已经表明有一个 传达配对信息的系统之间的明显区别 作为传达有关无害刺激信息的系统 灵长类动物丘脑。 我们建议接收输入的丘脑电路 由于受影响的脊髓段将因 周围神经损伤。 在人类中，疼痛通常是周围神经损伤的结果 这里提出的研究可能导致基于理性疗法的设计 了解脊柱神经回路的改变 周围神经损伤后的绳索和丘脑。 特别是我们 假设绳索和丘脑的抑制作用是 受神经损伤后的变化，我们更好地了解 紧随其后发生神经系统的重组 周围神经损伤，改进的药理疗法 解决这些变化最终可能会开发出来。