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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.

项目总结

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）

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

DOI：
10.3389/fpain.2023.1183553
发表时间：
2023
期刊：
FRONTIERS IN PAIN RESEARCH
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.

Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons.

DOI：
10.3390/md21020110
发表时间：
2023-02-02
期刊：
Marine drugs
影响因子：
5.4
作者：
通讯作者：

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

DOI：
10.1186/s12938-021-00870-y
发表时间：
2021-03-25
期刊：
Biomedical engineering online
影响因子：
3.9
作者：
DeLong M;Gil-Silva M;Hong VM;Babyok O;Kolber BJ
通讯作者：
Kolber BJ

Novel TRPV1 Modulators with Reduced Pungency Induce Analgesic Effects in Mice.

DOI：
10.1021/acsomega.1c05727
发表时间：
2022-01-25
期刊：
ACS omega
影响因子：
4.1
作者：
Treat A;Henri V;Liu J;Shen J;Gil-Silva M;Morales A;Rade A;Tidgewell KJ;Kolber B;Shen Y
通讯作者：
Shen Y

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