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：
8927343
负责人：
Katelyn Sadler
金额：
$ 3.84万
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 2017-09-21
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8927343
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 Major Depressive Disorder Maps Mediating Mitogen-Activated Protein Kinase 3 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就诊的主要原因之一。患有此类疾病（包括间质性膀胱炎/膀胱疼痛综合征）的患者，除了临床抑郁症和惊恐发作等情绪障碍外，通常还会出现骨盆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并发症的脊髓上处理，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，CeA 能够处理有害刺激并调节下行伤害感受通路。有趣的是，左右 CeA 调节对有害躯体刺激的不对称分子和行为反应。左、右 CeA 是否有差异地处理膀胱疼痛等有害内脏刺激，还有待观察。这些实验的目的是确定左右 CeA 之间膀胱疼痛偏侧化的生理程度以及这种现象的解剖学和分子机制。为了确定左右 CeA 是否差异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）；当动物的膀胱随着压缩空气水平的增加而膨胀时，光遗传学将允许激活或抑制左或右 CeA。为了进一步了解 CeA 不对称处理有害刺激背后的机制，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，重组病毒将用于研究左侧与右侧 CeA 产生的下降投射神经元的差异。