The impact of amygdala CGRP receptors on the development of persistent bladder pain.

杏仁核 CGRP 受体对持续性膀胱疼痛发展的影响。

• 批准号: 10613435
• 负责人: Lakeisha Lewter
• 金额: $ 7.38万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10613435
• 关键词: Acute; Affect; Aftercare; Amygdaloid structure; Animal Model; Animals; Area; Attention; Attenuated; Automobile Driving; Behavior; Biochemical; Bladder; Brain; Calcitonin Gene-Related Peptide; Calcitonin-Gene Related Peptide Receptor; Cell Nucleus; Cells; Central Lateral Nucleus; Central Nervous System; Chronic; Chronic Prostatitis; Clinical; Cyclophosphamide; Data; Development; Electrophysiology (science); Etiology; Experimental Designs; Functional disorder; Genetic; Goals; Human; Image; Individual; Injury; Interstitial Cystitis; Lateral; Learning; Left; Maintenance; Mediating; Modeling; Mus; Neurons; Neuropeptides; Nociception; Pain; Pain Research; Pathology; Patients; Pelvis; Play; Process; Reaction; Research; Research Personnel; Rodent; Role; Saline; Syndrome; Techniques; Testing; Time; Training; Viral; Visceral; Visceral pain; Work; Zymosan; antinociception; awake; bladder pain; cell type; chronic pain; chronic pelvic pain; cohort; in vivo; in vivo calcium imaging; inflammatory pain; insight; nerve injury; neurophysiology; novel; overexpression; pain model; painful neuropathy; parabrachial nucleus; persistent symptom; pharmacologic; receptor; targeted treatment; urologic chronic pelvic pain syndrome

PROJECT SUMMARY Urologic chronic pelvic pain syndrome (UCPPS) affects millions of individuals worldwide, and current treatments are limited due to their lack of efficacy. Although the underlying mechanisms of the development and maintenance of visceral pain are poorly understood, visceral pain is thought to engage brain circuits that may contribute to chronicity. The central nucleus of the amygdala (CeA) has received increasing attention as a significant region in the pathology of chronic pain. Findings from both human and rodent studies have revealed hemispheric lateralization of the CeA in pain modulation. While the right CeA has been shown to drive pain in models of somatic and visceral pain, the left CeA has been shown to attenuate visceral bladder pain. Recent evidence has implicated that CeA neuronal activity is not only asymmetric, but also changes with time once neuropathic pain is induced. However, it is unknown whether time-dependent activation of the CeA is prevalent in persistent bladder pain. I aim to further explore the hemispheric and temporal changes of the CeA in the context of bladder sensitization and injury, as well as identify cell-types that might be responsible for driving these changes. Calcitonin gene-related peptide (CGRP) is a neuropeptide that has been shown to produce divergent asymmetric functions within the CeA. In somatic pain, CGRP has been shown to have an antinociceptive function in the left CeA and a pronociceptive function in the right. However, little is understood about the role of CGRP and CGRP receptors in the brain in models of bladder pain. The overall objective of this proposal is to determine the influence of CGRP receptors on bladder pain-related lateralization over time. I will approach this goal by: 1) determining how CGRP receptor positive neurons (located in the right or left CeA) may influence pain-like behavior in two persistent bladder pain models, and 2) studying CeA activity of CGRP projection cells from the left or right parabrachial nucleus (PBn) in awake-behaving mice. Focusing on the contributions of CGRP receptors in visceral pain modulation could provide insight into the underlying mechanisms contributing to pain-related lateralization within the CeA. This, in turn, will lead to the development and advancement of effective CNS targeted therapies for bladder pain.

项目概要 泌尿科慢性盆腔疼痛综合征 (UCPPS) 影响着全世界数百万人，目前 由于缺乏疗效，治疗受到限制。尽管发展的根本机制 人们对内脏疼痛的发生和维持知之甚少，人们认为内脏疼痛会影响大脑回路 可能会导致慢性化。杏仁核中央核（CeA）作为一个重要的神经系统受到越来越多的关注。 慢性疼痛病理学中的重要区域。人类和啮齿动物研究的结果表明 CeA 在疼痛调节中的半球偏侧化。虽然右侧 CeA 已被证明可以减轻疼痛 在躯体和内脏疼痛模型中，左侧 CeA 已被证明可以减轻内脏膀胱疼痛。最近的 有证据表明，CeA 神经元活动不仅是不对称的，而且还会随时间而变化。 诱发神经性疼痛。然而，尚不清楚 CeA 的时间依赖性激活是否普遍存在。 持续性膀胱疼痛。我的目标是进一步探索 CeA 在半球和时间上的变化 膀胱敏感和损伤的背景，以及识别可能负责驾驶的细胞类型 这些变化。降钙素基因相关肽（CGRP）是一种神经肽，已被证明可以产生 CeA 内不同的不对称功能。在躯体疼痛中，CGRP 已被证明具有 左侧 CeA 具有抗伤害感受功能，右侧 CeA 具有促伤害感受功能。然而了解甚少 关于膀胱疼痛模型中 CGRP 和大脑中 CGRP 受体的作用。总体目标 该提案旨在确定 CGRP 受体随时间推移对膀胱疼痛相关偏侧化的影响。我 将通过以下方式实现这一目标：1) 确定 CGRP 受体阳性神经元（位于右侧或左侧 CeA）如何 可能会影响两种持续性膀胱疼痛模型的疼痛样行为，2) 研究 CGRP 的 CeA 活性 来自清醒小鼠左侧或右侧臂旁核（PBn）的投射细胞。专注于 CGRP 受体在内脏疼痛调节中的贡献可以提供对潜在机制的深入了解 导致 CeA 内疼痛相关偏侧化的机制。这反过来又会导致发展 以及针对膀胱疼痛的有效中枢神经系统靶向治疗的进展。