Central mechanisms of itch transmission

摘要 慢性瘙痒是一种与多种皮肤、免疫和神经疾病相关的未被治疗的医学问题。一个 瘙痒的兴奋性和抑制性传递失衡可能与慢性瘙痒的发病机制有关。 了解瘙痒传播的抑制机制对于开发靶向止痒药物具有重要意义 治疗。表达胃泌素释放肽受体(GRPR)的脊髓间神经元在瘙痒中起关键作用 变速箱。最近的研究表明，表达神经激肽3受体的抑制神经元的亚群 (TacR3)可能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抑制神经元通过抑制GRPR神经元抑制瘙痒而不是疼痛。目标1将 测定TacR3抑制神经元的解剖和电生理特性。目标2将决定 脊髓TacR3抑制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能传递。这些研究应该对脊柱有基本的洞察力 通过疼痛抑制瘙痒的机制。

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.