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

尽管疼痛令人不快，但对所有动物来说都是至关重要的。疼痛是一种警告信号，可以保护正常组织免受伤害，也可以保护受损组织免受进一步伤害。人类对疼痛的体验千差万别：对于同样的疼痛刺激，人们的反应是不同的。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是不同的；也就是说，疼痛信息在神经系统中的传递和编码方式是不同的。我研究的长期目标是确定疼痛处理的差异。我们目前研究的重点是疼痛的体验是如何随时间变化的。当疼痛刺激（如热探针）长时间施加时，即使探针的温度保持不变，痛觉也会波动。疼痛的这种特征被称为调节，部分原因在于神经系统中的处理过程。调制可以放大（放大）或抑制（降低）疼痛。我的实验室正在努力确定大脑和脊髓中的哪些回路调节疼痛，以及如何调节疼痛。******我们在人类受试者中进行两种类型的实验。在一项测试中，一个热的（45摄氏度）探针被应用到手上。给受试者一个控制器，调整探针温度，使探针的感觉保持恒定。如果受试者将体温调高，这表明抑制调节正在发生；探针的温度没有改变，但神经系统报告探针正在变冷（或疼痛减轻）。相反，如果受试者降低体温，神经系统就会放大传入的疼痛信号。******在另一项测试中，我们使用同样的热探针，测量神经递质的浓度，这种化学物质允许神经细胞在大脑和脊髓中进行交流。我们将使用一种尖端技术（MRS）：这项技术使我们能够安全、无创地测量体内化学物质的浓度，而不会从神经系统中清除液体。******疼痛研究领域受到限制，依赖于要求受试者对疼痛进行评级的测试。相反，这里描述的测试提供了关于疼痛处理的客观信息。要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，识别控制我们对疼痛感知的回路是至关重要的第一步。**

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. **