Physiology of Lamina I and V STT Cells

Lamina I 和 V STT 细胞的生理学

• 批准号: 6683189
• 负责人: ARTHUR D CRAIG
• 金额: $ 37.38万
• 依托单位: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6683189
• 关键词: Aotus; Macaca fascicularis; analgesia; basal lamina; central neural pathway /tract; cold temperature; microelectrodes; neurons; nontherapeutic iontophoresis; pain; pruritis; sensory mechanism; thermoreception

The spinothalamic tract (STT) is an important ascending pathway for activity associated with pain, temperature and itch sensations in primates and humans. Prior studies in this laboratory indicate that modality- selective lamina I STT neurons that project in the lateral STT have a integral role in these sensations. Studies in other laboratories, hoever, report that the responses of 'wide dynamic range' (WDR) STT neurons in lamina V, which ascend in the anterior STT, correlate with pain sensation and with hyperalgesia. Indeed, neurons in both populations are activated by stimulate that evoke pain, temperature, and itch sensations, yet both comprise several subclasses of cells that are activated by particular stimuli. This project is based on the global hypothesis that subclasses of lamina I and lamina V STT neurons carry complementary information to the forebrain that must be integrated to produce the several aspects of these sensations This hypothesis is consistent with clinical data suggesting that multiple ascending pathways are involved in pain, and with imaging observations showing that multiple forebrain regions are activated during these sensations. Knowledge of the activity in different subclasses of laminae I and V STT neurons that project to different targets in the primate thalamus is inadequate, despite considerable prior work. For example, polymodal nociceptive (HPC) lamina I STT cells that project to Vmpo have never been characterized, and the role of lamina V STT cells that project to VPL in the thermal grill illusion of pain has never been examined. In order to test specific hypothesis that anticipate which subclasses of laminae I aNd V STT cells display responses corresponding to different sensations, we will functionally characterize single laminae I and V STT neurons using five noel quantitative stimulus paradigms that distinguish different aspects of these sensations: (Aim 1) repeated brief contact heat [,second pain']; (Aim 2) graded tonic pressure ['first pain']; (Aim 3) iontophoretic histamine [itch]; (Aim 4) the algogens capsaicin and mustard oil (burning pain and hyperalgesia]; and (Aim 5) the thermal grill [illusory cold pain]. Using protocols that hae been refined in experiments in cats (which have almost no WDR lamina I STT cells and comparatively few lamina V STT cells), the goal of these experiments will be to obtain data in macaque monkeys that can be directly compared (across primates) with published human psychophysical evidence obtained using the same stimulus paradigms. Preliminary findings verify the feasibility of these experiments and validate the discriminative value of these paradigms. This research will provide new insights into the synergy between lamina I and V STT neurons and into the integration underlying pain, temperature and itch sensations that is altered in clinical disorders.

脊丘脑束(STT)是灵长类动物和人类与疼痛、温度和瘙痒相关的活动的重要上行通路。本实验室先前的研究表明，投射在外侧STT的I型选择性板层STT神经元在这些感觉中起着不可或缺的作用。然而，其他实验室的研究报告称，在前部STT上升的第V板层的宽动态范围(WDR)STT神经元的反应与痛觉和痛觉过敏有关。事实上，这两个群体中的神经元都是由引起疼痛、温度和瘙痒感觉的刺激激活的，但两者都包括由特定刺激激活的几个亚类细胞。这个项目是基于这样一种全球假设，即I层和V层STT神经元的亚类携带补充信息到前脑，必须整合这些信息才能产生这些感觉的几个方面。这一假说与临床数据一致，表明多条上升通路与疼痛有关，而且成像观察显示，在这些感觉过程中，多个前脑区域被激活。尽管之前的工作相当多，但对投射到灵长类丘脑不同靶点的I层和V层STT神经元的不同亚类的活动的了解还不够充分。例如，投射到Vmpo的多模式伤害性感受性(HPC)板层I STT细胞从未被表征，投射到VPL的板层V STT细胞在热烤痛觉错觉中的作用从未被研究过。为了测试预测板层I和V层的哪些亚类STT细胞显示对应于不同感觉的反应的特定假设，我们将使用五种区分这些感觉的不同方面的NOEL定量刺激范例来从功能上表征I层和V层的单层STT神经元：(目标1)重复短暂接触热[，第二次疼痛]；(目标2)分级紧张压[‘第一痛’]；(目标3)离子透入性组胺[痒]；(目标4)变应原辣椒素和芥子油(灼痛和痛敏)；(目标5)热烧烤[幻觉冷痛]。使用在猫的实验中改进的方案(几乎没有WDR I层STT细胞和相对较少的V层STT细胞)，这些实验的目标将是获得猕猴的数据，这些数据可以直接与(跨灵长类)公开的人类心理物理证据进行比较，这些证据是使用相同的刺激模式获得的。初步研究结果验证了这些实验的可行性，并验证了这些范式的区分价值。这项研究将为I层和V层STT神经元之间的协同作用以及临床疾病中改变的疼痛、温度和瘙痒感觉的整合提供新的见解。