Psychophysical Studies of Itch

瘙痒的心理物理学研究

• 批准号: 7762395
• 负责人: ROBERT H LA MOTTE
• 金额: $ 28.98万
• 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762395
• 关键词: Accounting; Afferent Neurons; Attenuated; Axon; Back; Burn injury; Capsaicin; Chemicals; Chronic; Clinical; Cutaneous; Cysteine Protease; Data; Disease; Dysesthesias; Esthesia; Exhibits; Fiber; Funding; Future; Grant; Hand; Heating; Histamine; Human; Human Volunteers; Hyperalgesia; Instruction; Lead; Left; Measurement; Measures; Mechanics; Mediating; Methods; Modality; Myelinated nerve fiber; Neuraxis; Neurons; Nociception; Nociceptors; Outcome Study; Pain; Pathway interactions; Peptide Hydrolases; Peripheral; Property; Pruritus; Psychophysiology; Role; Sensory; Signal Transduction; Site; Skin; Stimulus; Sting Injury; Structure of radial nerve; Testing; Time; base; desensitization; heat stimulus; nervous system disorder; neuromechanism; pressure; response; therapy design

Chemical activation of nociceptive neurons may contribute to chronic itch and pain in many disorders of the nervous system. During the last funding period, we determined that cowhage produces itch by a non¿ histaminergic mechanism, and we identified the pruritic agent in cowhage to be a cysteine protease. Endogenous proteases may contribute to clinical pruritus and pain. Using, among other stimuli, a new method of punctate application of a chemical that has been loaded into a heat-inactivated spicule of cowhage, we will psychophysically measure itch, pain and itchy skin (enhanced itch or pain) in human volunteers. Our aims are the following: (1) We will determine whether itch, pain, and cutaneous dysesthesias (enhanced itch or pain) from punctate application of mechanical or chemical pruritic stimuli such as an endogenous cysteine protease, are mediated by capsaicin sensitive primary afferent neurons; (2) We will test whether co-activation of the histaminergic and non-histaminergic pathways leads to the prolongation or enhancement of pruritic and nociceptive sensations and dysesthesias; (3) We will study the inhibitory effects of scratching, heating and algogenic chemicals on itch, pain and itchy skin while teasing apart the separate roles of stimulus modality (type of neuron activated), locus and intensity. (4) We will us a pressure block of conduction in myelinated nerve fibers to exam the separate roles of nociceptors with myelinated vs. non¿ myelinated axons in chemically and mechanically evoked itch, nociceptive sensations and dysesthesias. The outcomes of these studies will increase understanding of how itch and pain and dysesthetic states can co¿ exist as in certain clinical disorders; and how one or another sensory quality or dysesthetic state can be enhanced or inhibited. These psychophysical studies in human will provide a set of sensory conditions that must be accounted for by the responses of candidate pruriceptive and nociceptive-specific sensory neurons in the peripheral and central nervous system. RELEVANCE (See instructions): Psychophysical measurements of experimentally produced itch, pain and itchy skin in humans will further our understanding of the sensory conditions contributing to clinical pruritus and point to their underlying neural mechanisms. These mechanisms provide targets for future pharmacological therapies designed to relieve itch and pain in humans.

伤害性神经元的化学激活可能导致许多疾病的慢性瘙痒和疼痛 神经系统。在上一个资助期间，我们确定牛不会通过非自然因素产生瘙痒。 组胺能机制，我们鉴定出牛体内的瘙痒剂是半胱氨酸蛋白酶。 内源性蛋白酶可能导致临床瘙痒和疼痛。除其他刺激外，使用一种新的 点状施用化学物质的方法，该化学物质已装载到热灭活的针状体中 牛，我们将从心理物理角度测量人类的瘙痒、疼痛和皮肤瘙痒（增强的瘙痒或疼痛） 志愿者。我们的目标如下： (1) 我们将确定是否有瘙痒、疼痛和皮肤感觉迟钝 （加剧的瘙痒或疼痛）来自点状施加机械或化学瘙痒刺激，例如 内源性半胱氨酸蛋白酶，由辣椒素敏感的初级传入神经元介导； (2) 我们将 测试组胺能和非组胺能途径的共同激活是否会导致延长或 增强瘙痒和伤害性感觉以及感觉迟钝； (3) 研究抑制作用 抓挠、加热和致痛化学物质对瘙痒、疼痛和发痒的皮肤进行梳理，同时梳理分离的皮肤 刺激方式（激活的神经元类型）、位置和强度的作用。 (4) 我们将使用一个压力块 有髓神经纤维的传导，以检查有髓神经纤维与无髓神经纤维的伤害感受器的不同作用。 有髓轴突通过化学和机械方式引起瘙痒、伤害性感觉和感觉迟钝。这 这些研究的结果将增加人们对瘙痒、疼痛和感觉障碍如何相互影响的理解。 存在于某些临床疾病中；以及一种或另一种感觉质量或感觉障碍状态如何 增强或抑制。这些对人类的心理物理学研究将提供一系列的感觉条件， 必须通过候选瘙痒和伤害性特异性感觉神经元的反应来解释 在周围和中枢神经系统中。 相关性（参见说明）： 对人类实验产生的瘙痒、疼痛和皮肤瘙痒进行心理物理学测量将进一步促进我们的研究 了解导致临床瘙痒的感觉条件并指出其潜在的神经元 机制。这些机制为未来的药物治疗提供了目标，旨在缓解 人类的瘙痒和疼痛。