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.

Spinothalamic道（STT）是与灵长类动物和人类疼痛，温度和瘙痒相关的活动的重要上升途径。该实验室的先前研究表明，横向STT中突出的模态选择性椎板I STT神经元在这些感觉中具有不可或缺的作用。在其他实验室的研究中，hoever报告说，在层中升高的Lamina V中“广泛的动态范围”（WDR）STT神经元的反应与疼痛感觉和Hypergersia相关。实际上，两个群体中的神经元都通过引起疼痛，温度和瘙痒感激活，但两者都构成了几个被特定刺激激活的细胞的子类。该项目基于全球假设，即椎板I和Lamina v Stt神经元的子类带有补充信息到前脑，必须集成以产生这些感觉的几个方面，该假设与临床数据一致，这表明临床数据表明，多个上升途径与疼痛有关，并且表明成像观察表明在这些感觉中激活了这些感觉。尽管先前的工作相当大，但了解将在灵长类动物丘脑中的不同目标的不同子类和V stt神经元的不同子类中的知识。例如，从未表征将投射给VMPO的多峰性伤害感受器（HPC）薄片I STT细胞，并且从未检查过lamina v STT细胞在疼痛的热烧烤幻觉中投射的作用。为了测试特定假设，即预测层层I和V stt细胞的哪些亚类显示与不同感觉相对应的响应，我们将使用五个NOEL定量刺激范式来表征单个Laminae I和V STT神经元，以区分这些感觉的不同方面： （AIM 2）分级强调压力['第一疼痛']； （AIM 3）离子遗传组胺[itch]； （目标4）算法辣椒素和芥末油（燃烧疼痛和痛觉过敏]；（目标5）热烤[虚幻的冷痛]。使用在猫的实验中进行完善的协议（几乎没有WDR层层I的sTT细胞，并且可以与lamina v stt细胞相比，几乎没有wdr层层），而麦克基则是直接的数据。使用相同的刺激范式获得的人类心理物理学证据。