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: 7129304
• 负责人: ERIC H CHUDLER
• 金额: $ 19.16万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7129304
• 关键词: basal ganglia; neurons; pain; thalamic nuclei; thalamus

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）：由基底神经节损伤（例如帕金森病（PD））引起的运动症状和潜在的神经病理学已被广泛描述。然而，基底神经节在体感功能（包括疼痛和伤害感受）中的作用在很大程度上被忽视了。拟使用电生理学方法探索基底神经节如何调节丘脑层内核中伤害性神经元对持续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计会增强丘脑神经元对持续伤害性三叉神经刺激的反应。第一个具体目标是通过测试 CPu 电刺激对丘脑层内核伤害性神经元反应性的影响，分析尾壳核 (CPu) 和丘脑层内核之间的连接性。通过电刺激激活 CPU 预计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。这些电生理学实验还将允许对伤害性丘脑纹状体通路进行功能表征。先前未曾描述过该丘脑纹状体通路。第二个具体目标是测试多巴胺耗竭对丘脑层内核中三叉神经伤害性神经元反应性的影响，并研究多巴胺耗竭如何影响疼痛行为。单侧向CPu注射6-羟基多巴胺以破坏含多巴胺的神经元，预计会改变丘脑层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，并将揭示新的多巴胺能疼痛调节系统。帕金森病患者观察到的疼痛可能是由这种疼痛调节系统受损引起的。这些研究将有助于解释帕金森病患者表现出的复杂的感觉症状，并可能提出减轻此类疼痛的新治疗策略。