Central Nerual Mechanisms Involved in the Control of Itch

描述（由申请人提供）：瘙痒是一个主要的临床问题，患有各种疾病和感染的患者都在寻求缓解。瘙痒和其他有害的反刺激阻断了对瘙痒的感知;然而，无论是神经回路还是参与抑制瘙痒的神经递质都是未知的。背角中的许多脊髓丘脑束（STT）神经元对致痒剂（瘙痒产生剂）作出反应，并被认为将初级传入神经感受器的活动与感知体验联系起来。猴子的初步研究结果表明，有害的反刺激可以抑制STT神经元的放电过程中的反应，以过敏剂。因此，本研究的主要目的是确定灵长类STT神经元中促肾上腺皮质激素诱发反应的抑制机制。细胞外记录将从确定对瘙痒产生剂组胺或cowhage（一种非组胺能的，因此具有临床相关性的促瘙痒原）有反应的单个逆行性鉴定的STT神经元进行。本项目的具体目的是确定：1）是否从脊髓上的网站下行通路参与抑制STT神经元的促凝血酶原诱发的反应;和2）是否抑制促凝血酶原诱发的STT反应需要抑制性神经递质GABA和/或甘氨酸。这些研究将有助于对瘙痒的全面理解，并开始解决其控制的神经机制。对于大多数日常瘙痒，快速抓挠将消除令人厌恶的感觉;然而，由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。有关控制瘙痒的大脑和脊髓机制的知识可能会导致更有效的治疗瘙痒和改善公众健康。

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.