Basal ganglia modulation of trigeminal intralaminar nuclei thalamic activity

基底神经节对三叉神经层内核丘脑活动的调节

• 批准号: 7268135
• 负责人: ERIC H CHUDLER
• 金额: $ 18.93万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268135
• 关键词: Affect; Animals; Basal Ganglia; Behavior; Behavioral; Cell Nucleus; Centromedian Thalamic Nucleus; Chemical Stimulation; Chemicals; Clinical Data; Clinical Research; Complex; Data; Dopamine; Electric Stimulation; Exhibits; Face; Formalin; Frequencies; Future; Goals; Human; Impairment; Injection of therapeutic agent; Intralaminar Nuclear Group; Light; Literature; Mechanical Stimulation; Mediating; Methods; Motor; Movement; Neostriatum; Neural Pathways; Neurons; Nociception; Nociceptive Stimulus; Oxidopamine; Pain; Parkinson Disease; Pathway interactions; Patients; Physiological; Play; Posture; Process; Range; Rattus; Reporting; Research; Research Personnel; Role; Sensory; Stimulus; Structure; Symptoms; System; Testing; Thalamic structure; Trigeminal Neuralgia; Trigeminal System; caudate nucleus; insight; neuropathology; neurophysiology; nigrostriatal pathway; nociceptive response; putamen; receptive field; research study; response; somatosensory; subcutaneous

DESCRIPTION (provided by applicant): The motor symptoms and underlying neuropathology resulting from damage to the basal ganglia such as that in Parkinson's disease (PD) have been described extensively. However, the basal ganglia role in somatosensory function, including that of pain and nociception, has been largely ignored. The proposed use of electrophysic-logical methods explores how the basal ganglia modulate the response of nociceptive neurons in the intralaminar nuclei of the thalamus to persistent trigeminal nociceptive stimuli. Our long range goal is to understand how the basal ganglia modulate nociceptive information. Dopaminergic degeneration of the nigrostriatal pathway is expected to enhance the response of thalamic neurons to persistent nociceptive trigeminal stimuli. The first specific aim is to analyze the connectivity between the caudate- putamen (CPu) and intralaminar nuclei of the thalamus by testing the effects of electrical CPu stimulation on the responsiveness of nociceptive neurons in the intralaminar nuclei of the thalamus. Activation of the CPu by electrical stimulation is expected to alter the discharge frequency of nociceptive thalamic neurons to noxious chemical and mechanical stimulation of the face. These electrophysiological experiments will also permit functional characterization,of a nociceptive thalamostriatal pathway. This thalamostriatal pathway has not been described previously. The second specific aim is to test the effects of dopamine depletion on the responsiveness of trigeminal nociceptive neurons in the intralaminar nuclei of the thalamus and investigate how dopamine depletions affects pain behavior. Unilateral injection of 6-hydroxydopamine into the CPu to destroy dopamine-containing neurons is expected to alter the evoked discharge frequency of nociceptive neurons in the intralaminar nuclei of the thalamus and increase nociceptive behavioral responses. These experiments will provide new insights about the role of the basal ganglia in pain and nociception and will shed light on a new dopaminergic pain modulatory system. It is possible that pain observed patients with PD is caused by an impairment of this pain modulatory system. These studies will help explain the complex sensory symptoms exhibited by patients with PD and may suggest new treatment strategies to alleviate such pain.

描述（由申请人提供）：基底神经节损伤（如帕金森病（PD））导致的运动症状和潜在神经病理学已被广泛描述。然而，基底神经节在躯体感觉功能中的作用，包括疼痛和伤害感受，在很大程度上被忽视了。建议使用电物理学方法探讨基底神经节如何调节丘脑板内核中的伤害性神经元对持续性三叉神经伤害性刺激的反应。我们的长期目标是了解基底神经节如何调节伤害性信息。黑质纹状体通路的多巴胺能变性预期增强丘脑神经元对持续性伤害性三叉神经刺激的反应。第一个具体目的是通过测试电刺激尾壳核（CPu）对丘脑板内核中伤害性神经元反应性的影响来分析尾壳核（CPu）与丘脑板内核之间的连接。预期通过电刺激激活CPu会改变伤害性丘脑神经元对面部有害化学和机械刺激的放电频率。这些电生理学实验也将允许伤害性丘脑纹状体通路的功能表征。这种丘脑纹状体通路以前没有被描述过。第二个具体目标是测试多巴胺耗竭对丘脑板内核中三叉神经伤害感受神经元的反应性的影响，并研究多巴胺耗竭如何影响疼痛行为。将6-羟基多巴胺单侧注射到CPu中以破坏含多巴胺的神经元，预期会改变丘脑板内核中伤害性神经元的诱发放电频率并增加伤害性行为反应。这些实验将为基底神经节在疼痛和伤害感受中的作用提供新的见解，并将揭示一种新的多巴胺能疼痛调节系统。PD患者的疼痛可能是由这种疼痛调节系统的损伤引起的。这些研究将有助于解释PD患者表现出的复杂感觉症状，并可能提出新的治疗策略来缓解这种疼痛。