Effects of Central Amygdala Lateralization on Descending Control of Bladder Pain

描述(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。患有此类疾病的患者，包括间质性膀胱炎/膀胱痛综合征，除了临床抑郁和恐慌发作等情绪障碍外，通常还会出现盆腔疼痛和尿频增加等生理症状。为了更好地了解调节内脏疼痛症状和共病的棘上加工，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。CEA作为杏仁核的主要信息输出核，能够处理伤害性刺激，调节下行的伤害性感受通路。有趣的是，左右两侧的CEA调节着对伤害性躯体刺激的不对称分子和行为反应。左侧和右侧CEA是否以不同方式处理有害的内脏刺激，如膀胱痛，仍有待观察。本实验的目的是确定左侧和右侧CEA之间的膀胱痛偏侧的生理范围以及这种现象的解剖学和分子机制。为了确定左侧和右侧CEA是否对膀胱疼痛的生理反应有不同的调制作用，将使用光遗传学和膀胱扩张，这是一种常见的啮齿动物膀胱伤害性感受模型；光遗传学将允许在动物的膀胱被越来越多的压缩空气扩张时，左侧或右侧CEA的激活或抑制发生。为了进一步了解非对称CEA处理有害刺激的机制，将使用免疫组织化学和病毒跟踪技术。在膀胱扩张后，疼痛诱导的神经元标志物的定位将与CEA中自然表达的神经递质进行比较，以获得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左侧CEA和右侧CEA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.