Central mechanisms of itch transmission

瘙痒传播的中枢机制

基本信息

批准号：
10545020
负责人：
ZHOUFENG CHEN
金额：
$ 50.97万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-01 至 2023-09-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10545020
关键词：
Ablation Acute Address Affect Afferent Neurons Anatomy Behavior Bombesin Receptor Brain Cells Data Dedications Development Disease Electrophysiology (science)Etiology Genetic Immune Injections Interneurons Label Mediating Medical Modeling Molecular Mus Neuroanatomy Neuromedin K Receptor Neurons Neuropeptides Neurotransmitters Nociception Nociceptors Pain Pathway interactions Persons Phenotype Property Pruritus Quality of life Role Skin Slice Spinal Spinal Cord Stimulus Substance P Synapses TACR3 gene Tachykinin Techniques Testing Vertebral column Work chronic itch design dorsal horn excitatory neuron experimental study gamma-Aminobutyric Acid genetic approach inflammatory pain inhibitory neuron insight interdisciplinary approach neuromechanism optogenetics pain inhibition patch clamp pharmacologic transmission process virus genetics

项目摘要

Abstract Chronic itch is an unmet medical problem associated with numerous skin, immune, and nervous diseases. An imbalance of excitatory and inhibitory transmission of itch may contribute to the etiology of chronic itch. Understanding of inhibitory mechanisms of itch transmission is important for developing targeted anti-itch therapies. The spinal cord interneurons expressing gastrin-releasing peptide receptor (GRPR) are crucial for itch transmission. Recent studies suggest that a subset of inhibitory neurons expressing neurokinin 3 receptor (TacR3) may be activated by pain for itch inhibition. We will employ an interdisciplinary approach to test the hypothesis that TacR3 inhibitory neurons inhibit itch but not pain by inhibiting GRPR neurons. Aim 1 will determine anatomic and electrophysiological properties of TacR3 inhibitory neurons. Aim 2 will determine the role of spinal TacR3 inhibitory neurons in itch inhibition. Aim 3 will determine whether TacR3 neurons inhibit GRPR neurons via GABAergic transmission. These studies should yield fundamental insight onto the spinal mechanisms by which itch is inhibited by pain.

抽象的慢性瘙痒是一个未得到解决的医学问题，与许多皮肤、免疫和神经疾病相关。一个瘙痒的兴奋性和抑制性传播的不平衡可能导致慢性瘙痒的病因。了解瘙痒传播的抑制机制对于开发有针对性的止痒药物非常重要疗法。表达胃泌素释放肽受体（GRPR）的脊髓中间神经元对于瘙痒至关重要传播。最近的研究表明，表达神经激肽 3 受体的抑制性神经元子集 (TacR3) 可能会被疼痛激活以抑制瘙痒。我们将采用跨学科的方法来测试假设 TacR3 抑制性神经元通过抑制 GRPR 神经元来抑制瘙痒，但不能抑制疼痛。目标1将确定 TacR3 抑制性神经元的解剖学和电生理学特性。目标 2 将确定脊髓 TacR3 抑制神经元在抑制瘙痒中的作用。目标 3 将确定 TacR3 神经元是否抑制 GRPR 神经元通过 GABA 能传输。这些研究应该对脊柱产生基本的了解疼痛抑制瘙痒的机制。