Effects of Central Amygdala Lateralization on Descending Control of Bladder Pain

中央杏仁核偏侧化对膀胱疼痛下行控制的影响

基本信息

批准号：
9127225
负责人：
Katelyn Sadler
金额：
$ 2.04万
依托单位：
DUQUESNE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-22 至 2017-01-08
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9127225
关键词：
Affect Affective Age Air American Amygdaloid structure Animals Attention Bladder Brain Brain region Cell Nucleus Cells Comorbidity Corticotropin-Releasing Hormone Data Development Diagnosis Emotional Emotional Disturbance Emotions Exhibits Figs - dietary Frequencies Goals Growth Halorhodopsins Health Imaging Techniques Immunohistochemistry Interneurons Interstitial Cystitis Label Left Link MAPK3 gene Major Depressive Disorder Maps Mediating Mitogen-Activated Protein Kinases Modeling Molecular Neurons Neurotransmitters Nociception Nociceptive Stimulus Nocturia Outcome Output Pain Pain Disorder Panic Attack Pathway interactions Patients Pattern Pelvic Pain Physiological Population Population Heterogeneity Population Projection Process Proteins Publishing Recombinants Reporting Research Personnel Rodent Model Route Site Stimulus Symptoms Synapses Techniques Testing Tracer Training United States Urination Viral Visceral Visceral pain Visit Woman Work affective disturbance base behavioral response bladder pain cell type chronic pain clinically relevant differential expression experience inflammatory pain molecular marker new therapeutic target novel novel therapeutics optogenetics protein expression recombinant virus research study response

项目摘要

DESCRIPTION (provided by applicant): Ongoing visceral pain is one of the principal causes of doctors' visits in the United States. Patients suffering from such conditions, including interstitial cystitis/ bladder pain syndrome, commonly experience physiological symptoms like pelvic pain and increases in urination frequency in addition to emotional disturbances like clinical depression and panic attacks. In order to better understand the supraspinal processing that mediates symptoms and co-morbidities of visceral pain conditions, we are investigating the central amygdala (CeA), a brain region known to process both nociceptive and affective information. As the major information output nucleus of the amygdala, the CeA is able to process noxious stimuli and modulate descending nociceptive pathways. Interestingly, the left and right CeA modulate asymmetrical molecular and behavioral responses to noxious somatic stimuli. It remains to be seen if the left and right CeA differentially process noxious visceral stimuli like bladder pain. The objective of these experiments is to determine the physiological extent of bladder pain lateralization between the left and right CeA and the anatomical and molecular mechanism of this phenomenon. In order to determine if the left and right CeA differentially modulate physiological responses to bladder pain, optogenetics and urinary bladder distension, a common model of rodent bladder nociception, will be used; optogenetics will allow activation or inhibition of the left or right CeA to occur while animals' bladders are being distended with increasing levels of compressed air. To further understand the mechanisms behind asymmetrical CeA processing of noxious stimuli, immunohistochemistry and viral tracing techniques will be used. Following bladder distension, localization of pain-induced neuronal markers will be compared to natively expressed neurotransmitters in the CeA to elicit specific cell types involved in visceral pain processing. Finally, recombinant viruses wil be used to study differences in descending projection neurons arising from the left versus the right CeA.

描述（由申请人提供）：持续的内脏疼痛是医生在美国就诊的主要原因之一。患有这种疾病的患者，包括间质性膀胱炎/膀胱疼痛综合征，通常会出现诸如骨盆疼痛之类的生理症状，除了临床抑郁症和恐慌发作之类的情绪障碍外，除了情绪障碍外，还会出现排尿频率的增加。为了更好地了解介导内脏疼痛状况的症状和合并症的脊柱上部加工，我们正在研究中央杏仁核（CEA），杏仁核（CEA）是一个已知的大脑区域，该区域已知可以处理伤害性和情感信息。作为杏仁核的主要信息输出核，CEA能够处理有害刺激并调节降低的伤害感受途径。有趣的是，左右CEA调节对有害体细胞刺激的不对称分子和行为反应。左和右CEA是否会差异地处理有害内脏刺激（如膀胱疼痛）还有待观察。这些实验的目的是确定左右CEA之间膀胱疼痛侧向化的生理程度以及该现象的解剖学和分子机制。为了确定左和右CEA是否会使用对膀胱疼痛的生理反应，将使用光遗传学和膀胱延伸，这是一种常见的啮齿动物膀胱伤伤害感受模型；光遗传学将使左或右CEA激活或抑制动物的膀胱随着压缩空气水平的增加而膨胀时发生。为了进一步了解有害刺激的不对称CEA处理背后的机制，将使用免疫组织化学和病毒追踪技术。膀胱扩张后，将疼痛诱导的神经元标记物的定位与CEA中的本质表达的神经递质进行比较，以引起与内脏疼痛处理有关的特定细胞类型。最后，将使用重组病毒来研究由左侧与右CEA引起的下降投影神经元的差异。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Central amygdala activation of extracellular signal-regulated kinase 1 and age-dependent changes in inflammatory pain sensitivity in mice.

DOI：
10.1016/j.neurobiolaging.2017.04.010
发表时间：
2017-08
期刊：
Neurobiology of aging
影响因子：
4.2
作者：
Sadler KE;Gartland NM;Cavanaugh JE;Kolber BJ
通讯作者：
Kolber BJ

Urine Trouble: Alterations in Brain Function Associated with Bladder Pain.

DOI：
10.1016/j.juro.2015.10.198
发表时间：
2016-07
期刊：
The Journal of urology
影响因子：
0
作者：
Sadler KE;Kolber BJ
通讯作者：
Kolber BJ

Divergent functions of the left and right central amygdala in visceral nociception.

DOI：
10.1097/j.pain.0000000000000830
发表时间：
2017-04
期刊：
Pain
影响因子：
7.4
作者：
Sadler KE;McQuaid NA;Cox AC;Behun MN;Trouten AM;Kolber BJ
通讯作者：
Kolber BJ

Postinflammatory hyperpigmentation after human cold pain testing.

人体冷痛测试后炎症后色素沉着过度。

DOI：
10.1097/pr9.0000000000000569
发表时间：
2016
期刊：
Pain reports
影响因子：
4.8
作者：
Wolz,MelissaJ;Sadler,KatelynE;Long,CaelaC;Brenner,DanielS;Kim,BrianS;Gereau4th,RobertW;Kolber,BenedictJ
通讯作者：
Kolber,BenedictJ