Itch neurons studied in vivo

体内研究的痒神经元

基本信息

批准号：
8320114
负责人：
ROBERT H LA MOTTE
金额：
$ 20.75万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-15 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8320114
关键词：
Ache Action Potentials Acute Afferent Neurons Agonist Animals Antimalarials Attention Axotomy Behavior Burn injury Calcium Cell model Chemicals Chloroquine Chronic Code Cutaneous Dose Esthesia Exhibits Generations Genes Genetic Heating Histamine Human Image In Vitro Label Link Measurement Measures Mechanics Mediating Mediator of activation protein Membrane Membrane Potentials Methods Modeling Molecular Molecular Genetics Mus Neuroglia Neurologic Neurons Nociception Nociceptors Outcome Pain Peripheral Pharmaceutical Preparations Physiological Preparation Property Quality of life Sensory Signal Transduction Spinal Ganglia Stimulus Sting Injury Systemic disease Testing Tissues Topical application Transgenic Mice base beta-Alanine chronic pain design drug development imaging modality in vivo intradermal injection molecular marker neuromechanism neuronal cell body patch clamp receptive field receptor research study response seryl-leucyl-isoleucyl-glycyl-arginyl-leucine

项目摘要

DESCRIPTION (provided by applicant): Chronic itch, like chronic pain, is clinically recognized as a major cause of suffering and loss in the quality of life. Although itch accompanies many neurological, dermatological and systemic diseases, it has received less attention than pain in studies of underlying peripheral neural mechanisms. There have been two general approaches to studying the physiological properties of dorsal root ganglion neurons that respond to chemical stimuli that evoke itch in humans or itch-associated behavior in animals. The first is to electrophysiologically record action potentials evoked in these neurons in response to a pruritic chemical applied to their cutaneous receptive fields. The second approach is to examine the cellular molecular mechanisms of chemical sensory transduction using the cell body (soma), dissociated and placed in culture, as a model of the peripheral terminal endings. In a test of this model, we will combine these two approaches and compare the response properties of the soma and the receptive field in the intact, visualized, nociceptive DRG neuron, in vivo. We will use genetic-molecular fluorescent markers to identify the soma of a particular type of DRG neuron in the anesthetized mouse. Action potentials will be recorded extracellularly from the soma in response to pruritic and algesic stimuli delivered to its cutaneous receptive field. Then pruritic chemicals that activated the receptive field will be topically applied to the soma and alterations in somal membrane excitability or intracellular calcium will be measured. Similar measurements will be obtained, for comparison, from acutely dissociated somas with the same fluorescent markers. If successful, the outcome will point to new methods of studying the underlying cellular mechanisms of how itch mediating chemicals are sensed in peripheral neurons, an important precursor to the development of drugs that will act specifically to block pathological itch in humans.

描述（由申请人提供）：慢性瘙痒与慢性疼痛一样，在临床上被认为是造成痛苦和生活质量下降的主要原因。尽管瘙痒伴随许多神经、皮肤病和全身性疾病，但在潜在的周围神经机制的研究中，它比疼痛受到的关注要少。有两种通用方法来研究背根神经节神经元的生理特性，这些神经元对引起人类瘙痒或动物瘙痒相关行为的化学刺激做出反应。第一个是电生理学记录这些神经元响应施加到其皮肤感受野的瘙痒化学物质而诱发的动作电位。第二种方法是使用分离并置于培养物中的细胞体（体细胞）作为外周末端的模型来检查化学感觉转导的细胞分子机制。在对该模型的测试中，我们将结合这两种方法，并比较体内完整、可视化、伤害性 DRG 神经元的体细胞和感受野的响应特性。我们将使用遗传分子荧光标记来识别麻醉小鼠中特定类型 DRG 神经元的体细胞。动作电位将在细胞外记录，从体细胞响应传递到其皮肤感受野的瘙痒和痛觉刺激。然后，激活感受野的瘙痒化学物质将局部应用于体细胞，并测量体细胞膜兴奋性或细胞内钙的变化。为了比较，将从具有相同荧光标记的急性解离体中获得类似的测量结果。如果成功，结果将指出研究外周神经元如何感知瘙痒介导化学物质的潜在细胞机制的新方法，这是开发专门阻止人类病理性瘙痒的药物的重要先驱。