Itch-specific brain circuit and dopaminergic gene polymorphisms influencing individual differences in itch perception

瘙痒特异性脑回路和多巴胺能基因多态性影响瘙痒感知的个体差异

• 批准号: 10735592
• 负责人: Hideki Mochizuki
• 金额: $ 33.44万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735592
• 关键词: Achievement; Affect; Alleles; Area; Binding; Brain; Brain Stem; Brain imaging; Brain region; Corpus striatum structure; Development; Disease; Dopamine; Dopamine D1 Receptor; Dopamine D2 Receptor; Dorsal; Esthesia; Etiology; Functional Magnetic Resonance Imaging; Genes; Genetic; Genetic Polymorphism; Genotype; Human; Individual Differences; Investigation; Location; Methods; Motivation; Motor; Neurotransmitters; Pain; Participant; Pathway interactions; Patients; Perception; Persons; Play; Prefrontal Cortex; Pruritus; Reporting; Research Project Grants; Research Proposals; Role; Signal Transduction; Spinal; Stimulus; Thalamic structure; Vertebral column; Work; brain based; chronic itch; genetic information; global health; imaging study; novel; pain sensation; success; therapeutic target

Abstract Itch is a global health problem, affecting tens of millions of people. The brain plays a crucial role in itch perception; thus the specific circuit for itch processing in the brain has the potential to become a therapeutic target for itch in a wide range of pruritic diseases. Our understanding about the brain mechanism of itch has advanced in the past decades. Previous studies identified a key brain circuit related to itch, which includes the ascending pathway projecting from the thalamus to the posterior insular cortex (pIC) and networks originating from the pIC. In addition, dopamine was found to be a key neurotransmitter associated with itch. These achievements have also identified two important topics that must be understood to develop effective itch treatment targeting the brain. First, the brain circuit of itch is similar to that of pain, though itch and pain are clearly distinct sensations. An itch-specific ascending pathway and network have not yet been identified within the circuit (an itch-specific circuit). Second, there could be dopaminergic gene polymorphisms that determine individual differences in itch perception. If such polymorphisms are identified, brain imaging studies focusing on these genes can identify key loci regulating itch perception within the itch-specific circuit. This line of work will eventually enable us to develop brain-based, tailored itch treatment. To this end, it is crucial to identify an itch- specific circuit and dopaminergic gene polymorphisms influencing individual differences in itch perception. Our research proposal will address this significant gap. Aims 1 and 2 will use fMRI to determine an itch-specific ascending pathway and network by comparing brain activity between itch and pain stimuli. Aim 3 will use our novel method for quantitatively assessing genetic impacts on itch to identify dopaminergic gene polymorphisms that influence individual differences in itch perception. Success of our project will eventually lead to the development of brain-based tailored itch treatment, which will advance the treatment of chronic itch regardless of the underlying etiology.

摘要 瘙痒是一个全球性的健康问题，影响着数千万人。大脑在瘙痒中起着关键作用 因此，大脑中处理瘙痒的特定回路有可能成为一种治疗方法。 作为治疗多种皮炎疾病瘙痒的靶点。我们对瘙痒的大脑机制的理解 在过去的几十年里取得了进步。以前的研究确定了一个与瘙痒有关的关键大脑回路，其中包括 从丘脑到后岛叶皮质（pIC）的上行通路和起源于 从pIC。此外，多巴胺被发现是与瘙痒相关的关键神经递质。这些 研究成果还确定了两个重要的主题， 针对大脑的治疗。首先，瘙痒的大脑回路与疼痛的大脑回路相似，尽管瘙痒和疼痛是相似的。 明显不同的感觉。一个瘙痒特异性的提升路径和网络还没有被确定 电路（瘙痒特定电路）。其次，多巴胺能基因多态性可能决定了 瘙痒感知的个体差异。如果这种多态性被确定，脑成像研究的重点是 这些基因可以鉴定在瘙痒特异性回路中调节瘙痒感知的关键位点。这行工作将 最终使我们能够开发出基于大脑的，量身定制的瘙痒治疗方法。为此，识别瘙痒是至关重要的- 特定回路和多巴胺能基因多态性影响瘙痒感知的个体差异。我们 研究计划将解决这一重大差距。目标1和2将使用fMRI来确定瘙痒特异性 通过比较瘙痒和疼痛刺激之间的大脑活动来研究上升通路和网络。Aim 3将使用我们的 用于定量评估遗传对瘙痒的影响以鉴定多巴胺能基因多态性的新方法 影响个体瘙痒感知的差异。我们项目的成功将最终导致 开发基于大脑的定制瘙痒治疗方法，无论如何都将推进慢性瘙痒的治疗 潜在的病因