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Modulating single cell types in the sensory nervous system

调节感觉神经系统中的单细胞类型

基本信息

批准号：
10522412
负责人：
Eric W Schmidt
金额：
$ 54.21万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10522412
关键词：
Address Affect Afferent Neurons Animal Disease Models Animal Model Animals Behavioral Biological Assay Biological Process Biology Cardiac Cells Chemicals Chemistry Chronic Constipation Data Development Disease Drug Targeting Elan brand of omega-conopeptide MVIIA Electrophysiology (science)Esthesia FDA approved Health Human Individual Ion Channel Lead Ligands Maps Mechanics Mediating Medical Mental Depression Methods Molecular Target Movement Natural Products Nervous system structure Neurons Neuropathy Neuropharmacology Pain Pain management Peripheral Persons Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacology Physiological Positioning Attribute Pruritus Reaction Role Sensory Signal Transduction Specificity Spinal Ganglia System Testing Therapeutic Therapeutic Agents Time Touch sensation Treatment Efficacy United States Ventilatory Depression Work addiction allodynia cell type cellular imaging chronic pain chronic pain management chronic painful condition debilitating pain drug action in vivo innovation microbiome nervous system disorder novel novel therapeutics opioid epidemic pain model pain sensation painful neuropathy programs receptor recruit response sensory system side effect somatosensory synergism therapeutic evaluation therapeutic target tool ziconotide

项目摘要

Project Summary/Abstract Some of the best drugs to study and to treat pain and other nervous system disorders originate in the diverse chemistry made by animals and their microbiomes. These chemicals evolved to mediate interactions between animals, often triggering very precise responses in animal neurons. In particular, sensory neurons are major targets because they provoke an almost immediate behavioral reaction from the receiving animal. In humans, the somatosensory nervous system is a major target for drugs to treat pain and other nervous system disorders. Here, we seek to understand how natural compounds from animals and the animal microbiome mediate somatosensory signaling. We will interrogate this problem at the level of individual subclasses of neurons. The sensory system encodes many distinct cell types, each of which is responsible for a very specific type of sensation. For example, there are several different types of neurons that sense different kinds of heat, cold, pain, touch, itch, and bodily position. By applying neuroactive ligands to these natural mixtures of sensory cells, we are able to immediately visualize compounds that target just a single subset of cells, such as those responsible for mechanical or cold pain. In turn, those ligands may provide good drugs or drug leads to mediate the chronic pain conditions that are primarily caused by damage to those neurons. This project will map the functional pharmacology of neurons responsible for sensation, with a focus on pain sensation and central control of pain. At the same time, we will discover new ligands with potential application as tool compounds or as new therapies for chronic pain and other neurological diseases. To do so, our specific aims are to: 1) Discover ligands that target specific cell types in the sensory neurons; 2) Test the therapeutic efficacy of ligands by strategically selecting animal models of disease; and 3) Characterize the physiological targets and off-targets of test compounds in synergy with medicinal chemistry.

项目总结/文摘