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.

本计划的项目 4 项目涉及以下方面的变化： 周围神经损伤后的中枢神经系统。 我们将使用 在大鼠和随后的猴子中建立实验性单神经病模型， 这会导致动物出现异常的疼痛行为 受影响肢体的姿势以及对无害事物的过度反应 刺激（异常性疼痛）以及有害刺激（痛觉过敏）。 一些研究人员表明，坐骨神经的部分结扎 老鼠的神经会导致大量老鼠的退化 神经中的有髓鞘和无髓鞘轴突。 在一项试点研究中，我们 已经表明，在结扎后 14 天，存在广泛的轴突和 大鼠脊髓背角的突触变性 动物表现出疼痛行为的时期。 其他研究有 表明背角的抑制电路受损 此类动物。 我们将使用轴突运输结合 免疫细胞化学、电子显微镜技术来检查 背角在不同时间跟随周围神经的电路 伤害作为与疼痛相关的行为首先表现出来，直到它 在两个月的时间里逐渐减弱。 我们的工作假设是 疼痛行为可能与背角的变化相关， 特别是在不同生存时间的 GABA 电路中。 这 该研究的第二个主要方面是对预测的检验 脊髓丘脑束受影响的节段到丘脑， 工作假设是电路发生变化 丘脑可以与配对行为的变化相关， 尤其是在猴子身上。 我们之前已经证明有一个 传达配对信息的系统之间也存在明显差异 作为传达无害刺激信息的系统， 灵长类动物丘脑。 我们建议丘脑电路接收输入 受影响的脊柱节段将由于以下原因而被修改 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会导致基于合理疗法的设计 基于对脊髓神经回路变化的了解 周围神经损伤后的脊髓和丘脑。 特别是，我们 假设脊髓和丘脑的抑制回路是 神经损伤后会发生变化，并且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，改进的药物疗法旨在 最终可能会制定解决这些变化的方案。