Central mechanisms of itch transmission

瘙痒传播的中枢机制

• 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
• 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

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 慢性瘙痒是与多种皮肤，免疫和神经疾病有关的未解决的医学问题。一个 瘙痒的兴奋性和抑制性传播的不平衡可能有助于慢性瘙痒的病因。 了解瘙痒传播的抑制机制对于开发目标反ic很重要 疗法。表达胃蛋白释放肽受体（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，表达神经运动素3受体的抑制性神经元的子集 （TACR3）可能会因瘙痒抑制而被激活。我们将采用跨学科的方法来测试 假设TACR3抑制性神经元可以通过抑制GRPR神经元抑制瘙痒，但不能抑制疼痛。目标1意志 确定TACR3抑制性神经元的解剖学和电生理特性。 AIM 2将确定 脊柱TACR3抑制性神经元在瘙痒抑制中的作用。 AIM 3将确定TACR3神经元是否抑制 GRPR神经元通过GABA能传播。这些研究应对脊柱产生基本洞察力 瘙痒被疼痛抑制的机制。