Central Nerual Mechanisms Involved in the Control of Itch

参与控制瘙痒的中枢神经机制

• 批准号: 7275086
• 负责人: Steve Davidson
• 金额: $ 3.19万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-12 至 2010-03-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275086
• 关键词: Absence of pain sensation; Address; Analgesics; Atopic Dermatitis; Automobile Driving; Bicuculline; Brain; Brain Stem; Cell Nucleus; Cells; Cervical spinal cord structure; Cholestasis; Chronic; Clinical; Disease; Esthesia; Failure; Glycine; Goals; HIV; Heating; Histamine; Histamine Agents; Hodgkin Disease; Individual; Infection; Interneurons; Knowledge; Lead; Link; Mediating; Medical; Monkeys; Nervous system structure; Neurons; Neurotransmitters; Numbers; Pain; Pathway interactions; Patients; Perception; Personal Satisfaction; Physiological; Play; Positioning Attribute; Primates; Process; Pruritus; Public Health; Research Proposals; Role; Site; Skin; Specificity; Spinal; Spinal Cord; Spinothalamic Tracts; Stimulus; Strychnine; Symptoms; Testing; Thinking; brain pathway; clinically relevant; design; dorsal horn; experience; extracellular; gamma-Aminobutyric Acid; improved; midbrain central gray substance; mind control; neural circuit; neuromechanism; phaclofen; response

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.

描述（由申请人提供）：瘙痒是一个主要的临床问题，患有多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碍了瘙痒的感知；但是，既不知道抑制瘙痒的神经回路或神经递质。背喇叭中的许多脊柱丘脑（STT）神经元对培养基（瘙痒产生剂）反应，并被认为可以将主要传播性疗程的活性与感知体验联系起来。猴子中的初步发现表明，有害的反刺激可以抑制对鲁尿剂剂的反应期间Stt神经元的排出。因此，这项拟议的研究的主要目标是确定导致灵长类动物STT神经元中瘙痒症状反应的抑制的机制。细胞外记录将从单一的，抗细胞鉴定的STT神经元对瘙痒产生毒剂组胺或牛肝的反应（一种非 - 抗二胺能，因此与临床相关的瘙痒）进行反应。该项目的具体目的是确定：1​​）来自脊柱上部位的下降途径是否参与抑制急诊蛋白诱发的急诊术的反应； 2）抑制瘙痒的抑制作用是否需要抑制性神经递质GABA和/或甘氨酸。这些研究将有助于对瘙痒的整体理解，并开始解决其控制的神经机制。对于大多数日常瘙痒，快速划痕会消除厌恶的感觉。但是，由疾病或感染引起的瘙痒是推动个人寻求专业医疗的主要症状之一。该研究建议的目的是确定神经系统如何控制瘙痒。关于控制瘙痒的大脑和脊髓机制的知识可能会导致更有效的瘙痒治疗方法并改善公共卫生。