Physiology of Lamina I and V STT Cells

脊髓丘脑束（STT）是灵长类动物和人类与疼痛、温度和瘙痒感觉相关的重要上行通路。本实验室先前的研究表明，模式选择性的I层STT神经元投射到外侧STT中，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STT前部上升的V层STT神经元的“宽动态范围”（WDR）反应与痛觉和痛觉过敏有关。的确，这两类人的神经元都能被引起疼痛、温度和瘙痒感觉的刺激激活，但它们都包含几个被特定刺激激活的细胞亚类。这个项目是基于一个整体假设，即I层和V层STT神经元的亚类向前脑携带互补的信息，这些信息必须被整合以产生这些感觉的几个方面。这个假设与临床数据一致，表明疼痛涉及多个上升通路，并且成像观察显示多个前脑区域在这些感觉中被激活。尽管之前有大量的工作，但对灵长类丘脑中不同亚类的I和V STT神经元的活动的了解是不充分的。例如，投射到Vmpo的多模伤害性（HPC） I层STT细胞从未被描述过，投射到VPL的V层STT细胞在热烤架疼痛错觉中的作用从未被研究过。为了验证预测I和V STT层细胞的哪些亚类对不同的感觉表现出相应的反应的特定假设，我们将使用区分这些感觉的不同方面的五种新的定量刺激范式来功能表征单个I和V STT层神经元：（目的1）重复短暂接触热[，第二次疼痛]；（目的2）渐进式紧张性压力[“首次疼痛”]；（目的3）离子电泳组胺[痒]；（实验4）高原辣椒素和芥末油（灼痛和痛觉过敏）；（实验5）热烤架（虚幻的冷痛）。使用在猫（几乎没有WDR层I STT细胞和相对较少的层V STT细胞）实验中改进的方案，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证据进行比较（跨灵长类）。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。

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.