Discovering mechanisms of pro-nociception: The role of spinal and supraspinal structures

发现促伤害感受机制：脊柱和脊柱上结构的作用

• 批准号: RGPIN-2016-05456
• 负责人: Kramer, John
• 金额: $ 2.62万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709720
• 关键词: Discovering; mechanisms; pro; nociception; role

Although it is unpleasant, pain is crucial for all animals. Pain is a warning signal, to protect normal tissue from damage, and damaged tissue from further harm. The human experience of pain is incredibly variable: people respond differently to the same painful stimulus. While there are multiple reasons for this, recent evidence suggests that different people may actually be wired differently; that is, there are differences in how pain information is transmitted and encoded in the nervous system. The long-term goal of my research is to identify differences in pain processing. The focus of our current research is how the experience of pain changes over time. When a painful stimulus (e.g., a hot probe) is applied for a long time, the perception of pain fluctuates, even if the temperature of the probe remains the same. This feature of pain is called modulation, and is due, in part, to processing that occurs in the nervous system. Modulation can either amplify (turn up) or inhibit (turn down) pain. My laboratory is working to identify which circuits in the brain and spinal cord modulate pain, and how. We perform two types of experiments in human subjects. In one test, a hot (45C) probe is applied to the hand. The subject is given a controller, and adjusts probe temperature so that the sensation of the probe remains constant. If the subject turns the temperature up, this indicates that inhibitory modulation is occurring; probe temperature hasn't changed, but the nervous system reports that the probe is getting cooler (or less painful). Conversely, if the subject turns the temperature down, the nervous system is amplifying the incoming, painful signal. In another test, we apply the same hot probe, and measure concentrations of neurotransmitters chemicals that allow nerve cells to communicate in the brain and spinal cord. We will use a cutting-edge technique (MRS): this technique allows us to measure the concentration of chemicals inside the body safely and non-invasively, without removing fluid from the nervous system. The field of pain research is limited by relying on tests that require subjects to rate their pain. In contrast, the tests described here provide objective information about pain processing. Identifying circuits that control our perception of pain is the crucial first step to understanding why two seemingly similar people respond so differently to a painful stimulus.

尽管疼痛令人不快，但对所有动物来说，疼痛都是至关重要的。疼痛是一个警告信号，以保护正常组织免受损害，并保护受损组织免受进一步伤害。人类对疼痛的体验是千变万化的：人们对同样痛苦的刺激的反应是不同的。虽然这有多种原因，但最近的证据表明，不同的人实际上可能有不同的连接方式；也就是说，疼痛信息在神经系统中的传输和编码方式存在差异。我研究的长期目标是找出疼痛处理过程中的差异。 我们目前的研究重点是疼痛体验如何随着时间的推移而变化。当长时间施加痛苦的刺激(例如，热探头)时，即使探头的温度保持不变，疼痛的感觉也会波动。疼痛的这种特征被称为调制，部分原因是神经系统中发生的处理。调制可以放大(调高)或抑制(调低)疼痛。我的实验室正在努力识别大脑和脊髓中哪些回路调节疼痛，以及如何调节。 我们在人类受试者身上进行了两种类型的实验。在一项测试中，将一个热的(45摄氏度)探头放在手上。受试者被给予一个控制器，并调整探头温度，以使探头的感觉保持恒定。如果受试者将温度调高，这表明正在发生抑制性调制；探头温度没有变化，但神经系统报告探头正在变冷(或疼痛减轻)。相反，如果受试者将体温调低，神经系统就会放大传入的痛苦信号。 在另一项测试中，我们应用了同样的热探头，并测量了神经递质化学物质的浓度，这些化学物质允许神经细胞在大脑和脊髓中进行交流。我们将使用尖端技术(MRS)：这项技术允许我们安全、非侵入性地测量体内化学物质的浓度，而不需要从神经系统移除液体。 疼痛研究领域受到依赖于要求受试者对他们的疼痛进行评级的测试的限制。相反，这里描述的测试提供了有关疼痛处理的客观信息。识别控制我们对疼痛的感知的回路是理解为什么两个看似相似的人对疼痛刺激的反应如此不同的关键第一步。