Impact of Amygdala Lateralization on Processing and Modulation of Bladder Pain

杏仁核偏侧化对膀胱疼痛处理和调节的影响

基本信息

批准号：
10736493
负责人：
BENEDICT J KOLBER
金额：
$ 58.97万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10736493
关键词：
3-Dimensional Absence of pain sensation Acute Affect Amygdaloid structure Analgesics Anatomy Animal Model Anxiety Area Behavior Bladder Bladder Control Bladder Injury Brain Calcitonin Gene-Related Peptide Calcitonin-Gene Related Peptide Receptor Cells Central Nervous System Chronic Chronic Prostatitis Clinical Clustered Regularly Interspaced Short Palindromic Repeats Cognitive Complex Computer Models Data Development Disease Electrophysiology (science)Emotional Emotions Failure Foundations Goals Heterogeneity Human Hyperalgesia Hypersensitivity Injury Interstitial Cystitis Laboratories Language Learning Left Limbic System Location Maintenance Measures Mediating Mediator Messenger RNA Modeling Molecular Mus Neurons Neuropeptides Nociception Output Pain Pain Disorder Pathologic Pathway interactions Patients Pelvic Pain Peptide Signal Sequences Peripheral Peripheral Nervous System Persistent pain Physiological Physiology Play Population Production Quality of life Recovery Regulation Research Rodent Model Role Sensory Side Slice Stress Structure of terminal stria nuclei of preoptic region Substantia Innominata Symptoms Syndrome Testing Time Viscera Visceral pain Work affective disturbance behavior test bladder pain cell type chronic pelvic pain clinically relevant effective therapy experimental study gray matter human model in vivo calcium imaging innovation insight knock-down new therapeutic target novel optogenetics pain chronification pain model pre-clinical prevent response three-dimensional modeling time use treatment site urologic urologic chronic pelvic pain syndrome visual processing zona incerta

项目摘要

PROJECT SUMMARY Urologic chronic pelvic pain syndrome (UCPPS) represents the most common type of chronic visceral pain disorder. Although dysregulation of peripheral inputs from the viscera likely account for a number of the symptoms UCPPS, a failure to understand and treat central nervous system (CNS) changes likely prevents complete recovery for affected patients. The long-term goal of our lab is to understand the extent to which areas in the brain are responsible for the development and maintenance of persistent pain and accompanying affective disturbances that exist within urologic conditions. Recent evidence has suggested that the central amygdala in the CNS may be an important locus for the interaction between visceral pain and anxiety, potentially serving as a driver for chronic conditions like UCPPS. By determining the role of the amygdala in animal models of bladder pain, insight will be provided into the underlying physiology of the human condition. Evidence from human and animal models has shown that the left and right amygdala may differentially regulate pain. Variances in left and right hemisphere activation are well described in human language production, visual processing, and complex planning tasks. Functional lateralization exists in emotional processing areas of the brain, including the amygdala, across multiple taxa where the right brain serves as a reactive center to stress and injury. This conservation suggests that lateralization of limbic circuits is an evolutionarily important phenomenon. The idea that dysregulation in lateralization might also play a significant role in disease is a novel concept with clinical relevance. UCPPS patients show lateralized changes in amygdala gray matter and lateralized amygdala functional connectivity to other areas in the CNS. We recently identified a key molecular mediator through which lateralization of the amygdala modulates bladder pain bi- directionally in mice depending on the side of the brain this neuropeptide is applied. The objective of this proposal is to dissect the impact of this neuropeptide during the transition of acute to persistent bladder pain in a rodent model including exploring the efferent circuits from the amygdala that mediate brain-induced analgesia or hyperalgesia for bladder pain. This objective will be met through three distinct but complementary specific aims. In Aim 1, we will determine the extent to which the development of persistent bladder pain alters left versus right amygdala lateralization. In Aim 2, we will manipulate specific efferent outputs from the amygdala to identify the unique analgesic versus hyperalgesic pathways. In Aim 3, we will incorporate new and existing physiology data to develop a realistic 3-dimensional computational model of the amygdala that can be used to predict laboratory results to progress bladder pain studies and therapies. Overall, this proposal will help determine the extent and mechanisms of amygdala activation during painful bladder stimulation and the mechanisms by which an overactive amygdala may contribute to bladder pain as seen in UCPPS.

项目概要泌尿科慢性盆腔疼痛综合征 (UCPPS) 是最常见的慢性内脏疼痛类型紊乱。尽管来自内脏的外周输入失调可能是许多症状 UCPPS，未能理解和治疗中枢神经系统 (CNS) 变化可能会阻止受影响的患者完全康复。我们实验室的长期目标是了解大脑中负责持续疼痛和伴随疼痛的发展和维持的区域泌尿科疾病中存在的情感障碍。最近的证据表明，中央中枢神经系统中的杏仁核可能是内脏疼痛和焦虑之间相互作用的重要部位，可能成为 UCPPS 等慢性病的驱动因素。通过确定杏仁核的作用膀胱疼痛的动物模型，将有助于了解人类状况的基本生理学。来自人类和动物模型的证据表明，左右杏仁核可能存在差异调节疼痛。人类语言很好地描述了左右半球激活的差异生产、视觉处理和复杂的规划任务。功能侧化存在于情感中大脑的处理区域，包括杏仁核，跨越多个类群，其中右脑充当对压力和伤害的反应中心。这种保守性表明边缘回路的侧化是一种进化上重要的现象。侧化失调也可能发挥重要作用在疾病中的作用是一个具有临床意义的新概念。 UCPPS 患者表现出单侧变化杏仁核灰质和侧化杏仁核与中枢神经系统其他区域的功能连接。我们最近确定了一个关键的分子介质，杏仁核的偏侧化通过该介质调节膀胱疼痛在小鼠中根据大脑的一侧定向应用这种神经肽。此举的目的建议剖析这种神经肽在急性膀胱疼痛向持续性膀胱疼痛转变过程中的影响啮齿动物模型，包括探索调节脑诱导的杏仁核传出回路膀胱疼痛的镇痛或痛觉过敏。这一目标将通过三个不同但互补的目标来实现具体目标。在目标 1 中，我们将确定持续性膀胱疼痛的发展程度左侧与右侧杏仁核偏侧化。在目标 2 中，我们将操纵来自杏仁核来识别独特的镇痛与痛觉过敏途径。在目标 3 中，我们将纳入新的和现有的生理学数据来开发真实的杏仁核 3 维计算模型用于预测实验室结果以推进膀胱疼痛研究和治疗。总体而言，该提案将帮助确定疼痛性膀胱刺激期间杏仁核激活的程度和机制以及杏仁核过度活跃可能导致膀胱疼痛的机制，如 UCPPS 中所见。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Erratum.

勘误表。

DOI：
发表时间：
2024-04-15
期刊：
影响因子：
10.6
作者：
通讯作者：

Developing a 3-D computational model of neurons in the central amygdala to understand pharmacological targets for pain.

开发中央杏仁核神经元的 3D 计算模型，以了解疼痛的药理学靶点。

DOI：
发表时间：
2023
期刊：
影响因子：
0
作者：
Miller Neilan, Rachael;Reith, Carley;Anandan, Iniya;Kraeuter, Kayla;Allen, Heather N;Kolber, Benedict J
通讯作者：
Kolber, Benedict J

Agent-based modeling of the central amygdala and pain using cell-type specific physiological parameters.

使用细胞类型特定的生理参数对中央杏仁核和疼痛进行基于代理的建模。

DOI：
发表时间：
2021
期刊：
影响因子：
4.3
作者：
Miller Neilan, Rachael;Majetic, Gabrielle;Gil;Adke, Anisha P;Carrasquillo, Yarimar;Kolber, Benedict J
通讯作者：
Kolber, Benedict J

How to differentiate induced pluripotent stem cells into sensory neurons for disease modelling: a functional assessment.

如何将诱导多能干细胞分化为用于疾病建模的感觉神经元：功能评估。

DOI：
发表时间：
2024-04-05
期刊：
影响因子：
7.5
作者：
Kalia, Anil Kumar;Rösseler, Corinna;Granja;Ahmad, Ayesha;Pancrazio, Joseph J;Neureiter, Anika;Zhang, Mei;Sauter, Daniel;Vetter, Irina;Andersson, Asa;Dussor, Gregory;Price, Theodore J;Kolber, Benedict J;Truong, Vincent;Walsh
通讯作者：
Walsh

Visceral pressure stimulator for exploring hollow organ pain: a pilot study.

用于探索中空器官疼痛的内脏压力刺激器：一项试点研究。