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）： 尽管其临床重要性，但瘙痒的神经基础知之甚少。为了解决这个问题，将人类瘙痒感的心理物理测量与猴子原发性传入和脊柱丘脑（STT）神经元中反应的神经生理学测量进行比较。在这3个项目中使用类似的实验方案将有助于识别灵长类动物中瘙痒的神经机制。项目1将对人类的瘙痒进行心理物理研究。形容词标记的量表将用于比较点状的机械和热刺激以及组胺和牛肝引起的瘙痒和疼痛感的大小和时间过程。这些刺激在唤起瘙痒和发痒的皮肤上的影响以及疼痛和非疼痛刺激对瘙痒和发痒的皮肤的抑制作用。项目2将在猴子进行神经生理研究，以确定主要传入神经纤维如何应对心理学研究中使用的同样的脑力和伤害性刺激。 机械不敏感和机械敏感的多峰神经纤维的单纤维记录将用于检验以下假设：主要传播物的亚集对鲁尿刺激有选择性地反应，并为瘙痒感提供外围信号。将测试其他特性，例如纤维对热量和电刺激的反应差异，以查看它们是否将候选人的Pruriceptors与伤害感受器区分开。项目3将在猴子进行神经生理研究，以确定STT神经元如何应对心理学研究中使用的同样的核和伤害性刺激。微抗肌刺激技术将鉴定出向丘脑的腹侧下部或后核投射的STT神经元。将搜索针对核刺激的特异性或有选择性反应的培养基STT神经元，对刺激引起刺激的刺激，并唤起瘙痒性皮肤的特征，并且在项目1中显示的非pruritic刺激的反应增强或减少了对瘙痒性刺激的反应。提供管理，仪器，统计和信息学的核心将有助于从每个项目获得的数据收集，分析和评估。通过增加对编码和调节瘙痒的外围和中心神经机制的理解，我们的合并研究将为新颖的疗法提供新的靶标，以缓解瘙痒。