Medial Pain Inputs to Monkey Anterior Cingulate Cortex

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，由周扣带和中扣带区组成。伤害性信息通过丘脑中线核和层内核传递，然而，脊髓丘脑束和丘脑棘网系统与中线核之间的联系从未直接传递给扣带皮层。一例伴有严重内脏疼痛的肠易激综合征，经心理治疗后症状减轻，扣带中部减少，岛叶前部活动增加。两种假设指导了这些研究：外展区32、25、24a-c和扣带中区32‘和24a’-d的功能是由不同的丘脑中线输入驱动的，这些核在伤害感觉和应激方面进行平行回路。每只动物在脊髓或尾侧背髓网状核处注射辣根过氧化物酶，在对侧扣带区和/或岛状区注射三种荧光葡聚糖胺逆行示踪剂，然后进行4种抗体的反应。特异性目的#1将用神经元特异性抗体和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将用多种具有相同摄取、运输和信号特性的荧光示踪剂确定中线核向周、扣带中部和岛叶皮质的投射。#3将在颈椎脊髓注射后用顺行辣根过氧化物酶评估中线核输入的地形。#4将利用尾侧髓核的辣根过氧化物酶来评估中线核输入的地形。#5将评估每个中线核中多巴胺-13羟化酶的重叠与脊髓丘脑和髓质核的输入，以确定丘脑中伤害性和应激回路的重叠。这些研究将提供第一个证据，证明丘脑中线到边缘皮层的不同投射，以及丘脑内侧的脊髓、髓质和蓝斑重叠的程度，以及前扣带和岛状皮质疼痛处理的感觉、情感和运动域的调节。内侧疼痛系统处理的机制将被确定，这将有助于解释人类成像研究，并协助开发客观的细菌和治疗慢性疼痛的精神后果的疗法。

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.