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）： 瘙痒的神经基础是知之甚少，尽管它的临床重要性。为了解决这个问题，将人类瘙痒感觉的心理物理学测量与猴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瘙痒的神经机制。项目1将对人类瘙痒进行心理物理学研究。将使用形容词标记的量表比较点状机械和热刺激以及组胺和牛饲料诱发的瘙痒和疼痛感觉的幅度和时程。将研究这些刺激在引起瘙痒和皮肤瘙痒中的作用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疼痛和伤害性刺激作出反应。 将使用来自机械不敏感和机械敏感多模态神经纤维的单纤维记录来检验初级传入神经的子集选择性地响应瘙痒刺激并提供用于瘙痒感觉的外周信号的假设。其他属性，如纤维对热和电刺激的反应差异，将被测试，看看它们是否区分候选的伤害感受器。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刺激和伤害性刺激作出反应。微逆向刺激技术将识别投射到丘脑腹后下核或后核的STT神经元。将对刺激感受性STT神经元进行研究，这些神经元特异性或选择性地对瘙痒刺激作出反应，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被项目1中所示的非瘙痒刺激增强或减弱，以增加或减少瘙痒。一个提供行政、仪器、统计和信息学的核心将便利收集、分析和评价从每个项目获得的数据。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。