Physiology of Lamina I and V STT Cells

Lamina I 和 V STT 细胞的生理学

• 批准号: 6829087
• 负责人: ARTHUR D CRAIG
• 金额: $ 37.92万
• 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 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6829087
• 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.

脊髓丘脑束（STT）是灵长类动物和人类中与疼痛、温度和瘙痒感觉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的形态选择性板层I STT神经元在这些感觉中具有不可或缺的作用。然而，其他实验室的研究报告称，在前STT中上升的V层中的“宽动态范围”（WDR）STT神经元的反应与疼痛感觉和痛觉过敏相关。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，但两者都包含几个由特定刺激激活的细胞亚类。这个项目是基于一个全球性的假设，即I层和V层STT神经元的亚类携带补充信息的前脑，必须整合产生这些感觉的几个方面。这个假设是一致的临床数据表明，多个上行通路参与疼痛，并与成像观察显示，多个前脑区域在这些感觉被激活。知识的活动，在不同的亚类板层I和V STT神经元，项目在灵长类动物丘脑的不同目标是不够的，尽管有相当多的工作。例如，投射到Vmpo的多模式伤害性（HPC）板层I STT细胞从未被表征过，投射到VPL的板层V STT细胞在疼痛的热格栅错觉中的作用从未被研究过。为了检验预测哪一个亚类的板层I和V STT细胞显示对应于不同感觉的反应的特定假设，我们将使用区分这些感觉的不同方面的五种诺埃尔定量刺激范例来功能性地表征单个板层I和V STT神经元：（Aim 1）重复的短暂接触热[，第二疼痛“];（Aim 2）分级的强直压力[，第一疼痛”];（目标3）离子电渗组胺[瘙痒];（目标4）致痛物质辣椒素和芥末油（烧灼痛和痛觉过敏）;（目标5）热烧烤[虚幻的冷痛]。使用在猫实验中改进的方案（几乎没有WDR板层I STT细胞和相对较少的板层V 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使用相同刺激范式获得的已发表的人类心理物理学证据进行比较（在灵长类动物中）。初步研究结果验证了这些实验的可行性和验证了这些范式的区分价值。这项研究将提供新的见解板I和V STT神经元之间的协同作用，并到整合潜在的疼痛，温度和瘙痒的感觉是改变临床疾病。