Psychophysical Studies of Itch

瘙痒的心理物理学研究

• 批准号: 8111282
• 负责人: ROBERT H LA MOTTE
• 金额: $ 27.85万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8111282
• 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。在最后的资金期间，我们确定Cowhage会通过非 组胺能机制，我们确定牛乳中的核剂是半胱氨酸蛋白酶。 内源性蛋白酶可能有助于临床瘙痒和疼痛。在其他刺激中使用了新的 点燃化学物质的点状方法，该化学物质已被加载到热灭活的spicule中 CowHage，我们将在人类的心理物理上测量瘙痒，疼痛和瘙痒的皮肤（增强的瘙痒或疼痛） 志愿者。我们的目标是以下内容：（1）我们将确定瘙痒，疼痛和皮肤发抖 （增强的瘙痒或疼痛）来自点状的机械或化学核刺激（例如 内源性半胱氨酸蛋白酶是由辣椒素敏感的原发性传入神经元介导的。 （2）我们会的 测试组敏能和非 - 抗胺能途径的共激活是否导致延长或 增强核和伤害感受的感觉以及发抖； （3）我们将研究抑制作用 瘙痒，疼痛和瘙痒性皮肤上的刮擦，加热和算法化学物质，分开分开 刺激方式（神经元激活的类型），基因座和强度的作用。 （4）我们将使我们有一个压力块 髓神经纤维的传导以检查伤害感受器的单独作用，并用髓鞘和非。 髓鞘的轴突在化学和机械上引起瘙痒，伤害感受和发抖。 这些研究的结果将增加对瘙痒，疼痛和主体状态如何能够同时发生的理解。 像某些临床疾病一样存在；以及一个或另一个或另一个感觉质量或动物虚构状态如何 增强或抑制。这些在人类中的心理物理研究将提供一系列的感官条件 必须由候选人的诊断和伤害性特异性感觉神经元的响应来解释 在周围和中枢神经系统中。 相关性（请参阅说明）： 实验产生的瘙痒，疼痛和人类皮肤发痒的心理物理测量将进一步 了解有助于临床瘙痒的感觉状况并指向其潜在神经 机制。这些机制为未来的药理疗法提供了旨在营救的药理疗法的目标 人类瘙痒和疼痛。