Neural Mechanisms of Itch

瘙痒的神经机制

• 批准号: 7091706
• 负责人: ROBERT H LA MOTTE
• 金额: $ 100.5万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7091706
• 关键词: clinical research; human subject; hyperalgesia; neurochemistry; neurophysiology; pain; pruritis; psychophysics; sensation; skin; skin hypersensitivity; stimulus /response

DESCRIPTION (provided by applicant): The neural basis of itch is poorly understood despite its clinical importance. To address the problem, psychophysical measurements of itch sensation in humans will be compared to neurophysiological measurements of responses in primary afferent and spinothalamic tract (STT) neurons of the monkey. The use of similar experimental protocols in the 3 projects will facilitate the identification of the neural mechanisms of itch in primates. Project 1 will conduct psychophysical studies of itch in humans. An adjective-labeled scale will be used to compare the magnitude and time course of itch and pain sensations evoked by punctate mechanical and heat stimuli and by histamine and cowhage. The effects of these stimuli in evoking itch and itchy skin and the inhibitory effects of painful and non-painful stimuli on itch and itchy skin will be investigated. Project 2 will conduct neurophysiological studies in monkey to determine how primary afferent nerve fibers respond to the same pruritic and nociceptive stimuli used in the psychophysical studies. Single fiber recordings from mechanically insensitive and from mechanically sensitive polymodal nerve fibers will be used to test the hypothesis that subsets of primary afferents respond selectively to pruritic stimuli and provide the peripheral signal for itch sensation. Other properties, such as differences in fiber responses to heat and electrical stimuli will be tested to see if they distinguish candidate pruriceptors from nociceptors. Project 3 will conduct neurophysiological studies in monkey to determine how STT neurons respond to the same pruritic and nociceptive stimuli used in the psychophysical studies. Micro-antidromic stimulation techniques will identify STT neurons that project to either the ventral posterior inferior or posterior nuclei of the thalamus. A search will be made for pruriceptive STT neurons that respond specifically or selectively to pruritic stimuli, become sensitized to stimuli that evoke the characteristics of itchy skin, and whose responses to pruritic stimuli are enhanced or reduced by the non-pruritic stimuli shown in Project 1 to increase or decrease itch. A core providing administration, instrumentation, statistics and informatics will facilitate the collection, analysis and evaluation of the data obtained from each project. By increasing our understanding of the peripheral and central neural mechanisms that code and modulate itch, our combined studies will provide new targets for novel therapies to relieve itch.

描述（由申请人提供）： 尽管瘙痒具有临床重要性，但其神经基础却知之甚少。为了解决这个问题，将对人类瘙痒感的心理物理学测量与对猴子初级传入和脊髓丘脑束（STT）神经元反应的神经生理学测量进行比较。在这三个项目中使用类似的实验方案将有助于识别灵长类动物瘙痒的神经机制。项目 1 将进行人类瘙痒的心理物理学研究。形容词标记的量表将用于比较由点状机械和热刺激以及组胺和牛引起的瘙痒和疼痛感觉的强度和时间过程。将研究这些刺激对引起瘙痒和皮肤瘙痒的影响以及疼痛和非疼痛刺激对瘙痒和皮肤瘙痒的抑制作用。项目 2 将在猴子身上进行神经生理学研究，以确定初级传入神经纤维如何对心理物理学研究中使用的相同瘙痒和伤害性刺激做出反应。 来自机械不敏感和机械敏感的多模态神经纤维的单纤维记录将用于测试初级传入神经的子集选择性地响应瘙痒刺激并提供瘙痒感的外周信号的假设。其他特性，例如纤维对热和电刺激反应的差异，将进行测试，看看它们是否能够区分候选瘙痒感受器和伤害感受器。项目 3 将在猴子身上进行神经生理学研究，以确定 STT 神经元如何对心理物理学研究中使用的相同瘙痒和伤害性刺激做出反应。微逆向刺激技术将识别投射到丘脑腹侧后下核或后核的 STT 神经元。将寻找瘙痒性 STT 神经元，这些神经元对瘙痒刺激有特异性或选择性反应，对引起皮肤瘙痒特征的刺激变得敏感，并且其对瘙痒刺激的反应会被项目 1 中所示的非瘙痒刺激增强或减弱。增加或减少瘙痒。提供管理、仪器、统计和信息学的核心将促进从每个项目获得的数据的收集、分析和评估。通过增加我们对编码和调节瘙痒的外周和中枢神经机制的理解，我们的联合研究将为缓解瘙痒的新疗法提供新的靶点。