Effects of Central Amygdala Lateralization on Descending Control of Bladder Pain

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。

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.