Central Nerual Mechanisms Involved in the Control of Itch

描述(由申请人提供)：瘙痒是一种主要的临床问题，患有各种疾病和感染的患者寻求缓解。抓挠和其他有害的反刺激阻断了对瘙痒的感知；然而，参与抑制瘙痒的神经回路和神经递质都不是很清楚。背角中的许多脊髓丘脑束(STT)神经元对瘙痒原(瘙痒产生物质)做出反应，并被认为将初级传入瘙痒感受器的活动与知觉经验联系起来。在猴子身上的初步发现表明，在对瘙痒药的反应中，有害的反刺激可以抑制STT神经元的放电。因此，这项研究的主要目的是确定抑制灵长类STT神经元瘙痒原诱发反应的机制。细胞外记录将从单个逆行鉴定的STT神经元进行，被确定为对瘙痒产生剂组胺或母牛饲料(一种非组胺能，因此与临床相关的瘙痒原)有反应。这个项目的具体目的是确定：1)脊髓上部位的下行通路是否参与抑制STT神经元的瘙痒原诱发反应；以及2)抑制瘙痒原引起的STT反应是否需要抑制性神经递质GABA和/或甘氨酸。这些研究将有助于全面了解瘙痒，并开始解决其控制的神经机制。对于大多数日常瘙痒来说，快速的瘙痒会消除这种厌恶的感觉；然而，疾病或感染引起的瘙痒是促使个人寻求专业医疗的主要症状之一。这项研究计划的目的是确定神经系统如何控制瘙痒。对控制瘙痒的大脑和脊髓机制的了解可能会导致更有效的瘙痒治疗，并改善公众健康。

DESCRIPTION (provided by applicant): Itch is a major clinical problem from which relief is sought by patients suffering from a variety of diseases and infections. Scratching and other noxious counter-stimuli block the perception of itch; however, neither the neural circuits nor the neurotransmitters involved in suppressing itch are known. Many spinothalamic tract (STT) neurons in the dorsal horn respond to pruritogens (itch producing agents) and are thought to link activity in primary afferent pruriceptors to perceptual experience. Preliminary findings in the monkey indicate that noxious counter-stimuli can inhibit the discharge of STT neurons during a response to a pruritic agent. Therefore, the major goal of this proposed study is to determine the mechanisms responsible for the inhibition of pruritogen evoked responses in primate STT neurons. Extracellular recordings will be performed from single, antidromically identified STT neurons determined to be responsive to the itch producing agent histamine or cowhage (a non-histaminergic and therefore clinically relevant pruritogen). The specific aims of this project are to determine: 1) whether a descending pathway from supraspinal sites is involved in inhibiting pruritogen evoked responses of STT neurons; and 2) whether the inhibition of a pruritogen evoked STT response requires the inhibitory neurotransmitters GABA and/or glycine. These studies will contribute to an overall understanding of itch and begin to address the neural mechanisms of its control. For most everyday itches, a quick scratch will abolish the aversive sensation; however, itch caused by disease or infection is one of the leading symptoms driving individuals to seek professional medical treatment. The aim of this research proposal is to determine how the nervous system controls itch. Knowledge about the brain and spinal cord mechanisms involved in the control of itch may lead to more effective treatments for itch and improve public health.