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.

脊髓丘脑束（STT）是灵长类动物和人类与疼痛、温度和瘙痒感相关的活动的重要上升通路。该实验室之前的研究表明，投射到外侧 STT 的模态选择性层 I STT 神经元在这些感觉中发挥着不可或缺的作用。然而，其他实验室的研究报告称，第五层中的“宽动态范围”(WDR) STT 神经元（在前 STT 中上升）的反应与痛觉和痛觉过敏相关。事实上，这两个群体中的神经元都会被引起疼痛、温度和瘙痒感的刺激激活，但两者都包含由特定刺激激活的几个细胞亚类。该项目基于这样的总体假设：I 层和 V 层 STT 神经元的亚类向前脑携带补充信息，必须整合这些信息才能产生这些感觉的多个方面。该假设与临床数据一致，表明多个上行通路与疼痛有关，并且成像观察表明在这些感觉期间多个前脑区域被激活。尽管之前进行了大量工作，但对投射到灵长类丘脑不同目标的 I 层和 V 层 STT 神经元不同亚类的活动的了解还不够。例如，投射到 Vmpo 的多模式伤害感受 (HPC) 层 I STT 细胞从未被表征，投射到 VPL 的层 V STT 细胞在热烤疼痛错觉中的作用也从未被研究过。为了测试预测哪些 I 层和 V STT 细胞亚类表现出与不同感觉相对应的反应的具体假设，我们将使用五种区分这些感觉不同方面的诺埃尔定量刺激范式对单个 I 层和 V STT 神经元进行功能表征：（目标 1）重复短暂接触热 [，第二次疼痛 ]； （目标 2）分级强直压力 ['第一痛']； （目标 3）离子导入组胺[痒]； （目标 4）生物质辣椒素和芥末油（灼痛和痛觉过敏）；以及（目标 5）热烧烤[虚幻的冷痛]。使用在猫实验中完善的方案（几乎没有 WDR I 层 STT 细胞和相对较少的 V 层 STT 细胞），这些实验的目标是获得猕猴的数据，这些数据可以直接比较（跨物种） 灵长类动物），并使用相同的刺激范例获得已发表的人类心理物理学证据。初步结果验证了这些实验的可行性，并验证了这些范式的判别价值。这项研究将为了解 I 层和 V 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。