Medial Pain Inputs to Monkey Anterior Cingulate Cortex

猴子前扣带皮层的内侧疼痛输入

• 批准号: 6984755
• 负责人: Brent Alan Vogt
• 金额: $ 27.46万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984755
• 关键词: Macaca fascicularis; biological signal transduction; calbindin; central neural pathway /tract; chronic pain; cingulate gyrus; comorbidity; dextrans; dopamine beta monooxygenase; horseradish peroxidase; irritable bowel syndrome; neurofilament; nociceptors; pain threshold; psychotherapy; stressor; thalamus; visceral afferent nerve

DESCRIPTION (provided by applicant): Anterior cingulate cortex is the most frequently activated cortex in human pain studies and is comprised of perigenual and midcingulate regions. Nociceptive information passes through the midline and intralaminar thalamic nuclei, however, links between the spinothalamic tract and spinoreticulothalamic system to the midline nuclei has never been made directly to cingulate cortex. A case of irritable bowel syndrome with severe visceral pain shows alleviation of symptoms with psychotherapy and reduced midcingulate and increased anterior insular activity. Two hypotheses guide these studies: Functions of perigenual areas 32, 25, 24a-c and midcingulate areas 32' and 24a'-d are driven by different midline thalamic inputs and these nuclei conduct parallel circuits for nociception and stress. Each animal will receive horseradish peroxidase either in the spinal cord or dorsocaudal medullary reticular nucleus, and three fluorescent dextran amine retrograde tracers in contralateral cingulate and/or insular areas followed by reactions for 4 antibodies. Specific Aim #1 will evaluate the immunoarchitecture of the midline and dorsocaudal medullary nuclei with a neuron-specific antibody and antibodies for neurofilaments and calbindin. #2 will determine the projections of the midline nuclei to perigenual, midcingulate, and insular cortices with multiple fluorescent tracers that have the same uptake, transport, and signal properties. #3 will evaluate the topography of inputs to the midline nuclei with anterograde horseradish peroxidase following cervical spinal cord injections. #4 will assess the topography of inputs to the midline nuclei with horseradish peroxidase in the dorsocaudal medullary nucleus. #5 will evaluate overlap of dopamine-13 hydroxylase in each of the midline nuclei with inputs from spinothalamic and medullary nuclei to determine the overlap of nociceptive and stress circuits in the thalamus. These studies will provide the first evidence for differential projections of the midline thalamus to limbic cortex and the extent of spinothalamic, medullary, and locus coeruleus overlap in the medial thalamus and modulatation of sensory, affective, and motor domains of pain processing in anterior cingulate and insular cortices. The mechanisms of medial pain system processing will be identified and this will help interpret human imaging studies and assist in developing objective cdteria and therapies for treating the psychiatric consequences of chronic pain.

描述（由申请人提供）：前扣带皮层是人类疼痛研究中最常激活的皮层，由膝周和中扣带回区域组成。伤害感受信息通过中线和层内丘脑核，然而，脊髓丘脑束和脊髓网状丘脑系统与中线核之间的联系从未直接与扣带皮层建立。一例伴有严重内脏疼痛的肠易激综合征病例显示，心理治疗可缓解症状，扣带回中部减少，岛叶前部活动增加。两个假设指导这些研究： 膝周区域 32、25、24a-c 和中扣带回区域 32' 和 24a'-d 的功能由不同的中线丘脑输入驱动，并且这些核团传导伤害感受和压力的并行电路。每只动物将在脊髓或背尾髓质网状核中接受辣根过氧化物酶，并在对侧扣带回和/或岛叶区域中接受三种荧光右旋糖酐胺逆行示踪剂，然后对 4 种抗体进行反应。具体目标#1 将使用神经元特异性抗体以及神经丝和钙结合蛋白抗体评估中线和背尾髓核的免疫结构。 #2 将使用具有相同摄取、运输和信号特性的多种荧光示踪剂确定中线核对膝周、中扣带皮层和岛叶皮质的投影。 #3 将评估颈脊髓注射后顺行辣根过氧化物酶对中线核输入的形貌。 #4 将评估背尾髓核中辣根过氧化物酶对中线核输入的形貌。 #5 将评估每个中线核中多巴胺 13 羟化酶与来自脊髓丘脑和髓质核的输入的重叠，以确定丘脑中伤害感受和应激回路的重叠。这些研究将为中线丘脑到边缘皮质的差异投影以及内侧丘脑中脊髓丘脑、延髓和蓝斑重叠的程度以及前扣带回和岛叶皮质中疼痛处理的感觉、情感和运动域的调节提供第一个证据。将确定内侧疼痛系统处理的机制，这将有助于解释人类成像研究，并协助开发治疗慢性疼痛的精神后果的客观标准和疗法。