Peripheral Neuronal Mechanisms of Itch

瘙痒的周围神经机制

• 批准号: 9764268
• 负责人: ROBERT H LA MOTTE
• 金额: $ 62.98万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-19 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764268
• 关键词: Acids; Acute; Adrenal Glands; Affect; Agonist; Allergic Contact Dermatitis; Antipruritics; C Fiber; Capsaicin; Cattle; Chemicals; Clinical; Code; Cutaneous; Dermatologic; Development; Disease; Electrophysiology (science); Esters; Esthesia; Fiber; Frequencies; Future; G-Protein-Coupled Receptors; Goals; Human; Hypersensitivity; Individual; Link; Mediating; Modeling; Monkeys; Mus; Nerve Fibers; Neurologic; Neurons; Neurotransmitters; Nociception; Nociceptors; Outcome; Pain; Patients; Pattern; Peripheral; Peripheral Nerves; Peripheral Nervous System; Pharmaceutical Preparations; Population; Primates; Proteins; Pruritus; Psychophysics; Quality of life; Role; Signal Transduction; Skin; Spinal Cord; Stimulus; Symptoms; Systemic disease; Testing; Time; Translating; beta-Alanine; chronic itch; clinically relevant; desensitization; excitatory neuron; experimental study; heat stimulus; inhibitory neuron; interest; nonhuman primate; novel; pain sensation; predictive modeling; response; treatment strategy

Itch accompanies many neurological, dermatological and systemic diseases and leads to suffering and loss in the quality of life. The peripheral neuronal mechanisms underlying this sensation in human are still poorly understood. The overall goal of our proposal is to determine how acute itch and the prolonged itch from a pruritic disease are encoded in the discharges of cutaneous nociceptors. We propose electrophysiological experiments in nonhuman primate to characterize the responses to pruritic chemical stimuli in subtypes of peripheral nociceptive nerve fibers and complementary, correlative psychophysical studies in human to determine the role of these different neuronal populations in itch sensation. We will test the predictions of models that propose that cutaneous nociceptors differentially signal pruritic and algesic stimuli either by the overall number of afferents activated or by the rates or patterns of their discharges. In a clinically relevant model of prolonged itch, namely the SADBE model of allergic contact dermatitis, we will investigate the neuronal mechanisms of spontaneous itch and enhanced itch to chemical and heat stimuli using psychophysical studies in humans and electrophysiological recordings from nociceptive afferents in monkeys. By studying both acute and prolonged itch, we will be able to identify, for the first time, changes that occur in the peripheral nervous system in a clinically relevant itch condition. A better understanding of how nociceptors mediate the sensation of itch in normal and pruritic skin will increase the possibility of developing and evaluating novel, peripherally acting drugs that reduce the abnormal nociceptor function underlying chronic itch.

瘙痒伴随着许多神经、皮肤和全身性疾病，并导致痛苦和损失， 生活品质人类这种感觉背后的外周神经机制仍然很差 明白我们建议的总体目标是确定急性瘙痒和长期瘙痒的程度， 皮肤伤害感受器的放电是皮肤炎性疾病的编码。我们建议电生理学 在非人灵长类动物中进行的实验，以表征 外周伤害性神经纤维和补充，相关的心理物理学研究， 确定这些不同的神经元群体在瘙痒感觉中的作用。我们将检验 模型提出，皮肤伤害感受器的差异信号刺激和痛觉刺激， 被激活的传入神经的总数，或由其放电的速率或模式决定。以临床相关 长时间瘙痒的模型，即变应性接触性皮炎的SADBE模型，我们将研究 自发性瘙痒和化学和热刺激增强瘙痒的神经元机制， 人类的心理物理学研究和猴子的伤害性传入的电生理学记录。 通过研究急性和长期瘙痒，我们将能够识别，第一次，发生的变化， 周围神经系统在临床上相关的瘙痒条件。更好地理解伤害感受器 在正常和过敏性皮肤中调解瘙痒的感觉将增加发展的可能性， 评价新型的外周作用药物，减少慢性伤害感受器功能异常， 发痒.