Effects of Central Amygdala Lateralization on Descending Control of Bladder Pain

描述（由申请人提供）：在美国，持续的内脏疼痛是就诊的主要原因之一。患有这些疾病的患者，包括间质性膀胱炎/膀胱疼痛综合征，通常会出现生理症状，如盆腔疼痛和排尿频率增加，以及临床抑郁和恐慌发作等情绪障碍。为了更好地了解介导内脏疼痛症状和并发症的椎骨上加工，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性通路。有趣的是，左侧和右侧的CeA调节着对有害躯体刺激的不对称的分子和行为反应。左、右CeA是否会对有害的内脏刺激（如膀胱疼痛）产生不同的反应还有待观察。本实验的目的是确定膀胱疼痛在左右CeA之间偏侧的生理程度及其解剖学和分子机制。为了确定左、右CeA是否对膀胱疼痛、光遗传学和膀胱膨胀的生理反应有差异调节，将使用一种常见的啮齿动物膀胱伤害感觉模型；光遗传学将允许激活或抑制左或右CeA发生，当动物的膀胱被增加的压缩空气水平膨胀。为了进一步了解不对称CeA处理有害刺激的机制，将使用免疫组织化学和病毒追踪技术。膀胱膨胀后，疼痛诱导的神经元标记物的定位将与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，重组病毒将被用于研究左侧和右侧CeA产生的下行投射神经元的差异。

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.