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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）：持续的内脏疼痛是美国医生就诊的主要原因之一。患有这种病症的患者，包括间质性膀胱炎/膀胱疼痛综合征，除了临床抑郁症和惊恐发作等情绪障碍外，通常还会出现盆腔疼痛和排尿频率增加等生理症状。为了更好地了解介导内脏疼痛症状和合并症的脊髓上处理，我们正在研究中央杏仁核（CeA），这是一个已知处理伤害性和情感信息的大脑区域。作为杏仁核的主要信息输出核团，CeA能够处理伤害性刺激并调节下行伤害性通路。有趣的是，左和右CeA调节不对称的分子和行为反应的伤害性躯体刺激。它仍然有待观察，如果左，右CeA差异处理伤害性内脏刺激，如膀胱疼痛。这些实验的目的是确定膀胱疼痛偏侧的生理程度之间的左，右CeA和这种现象的解剖和分子机制。为了确定左和右CeA是否差异性地调节对膀胱疼痛的生理反应，将使用光遗传学和膀胱扩张（啮齿动物膀胱伤害感受的常见模型）;当动物的膀胱用增加水平的压缩空气扩张时，光遗传学将允许激活或抑制左或右CeA。为了进一步了解背后的机制不对称CeA处理伤害性刺激，免疫组织化学和病毒示踪技术将被使用。膀胱扩张后，将疼痛诱导的神经元标记物的定位与CeA中天然表达的神经递质进行比较，以引出参与内脏疼痛处理的特定细胞类型。最后，重组病毒将被用来研究下行投射神经元的差异，从左与右CeA。

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