Studies of human psycho-physiological responses to visceral pain.

拟议研究的性质：虽然疼痛是一种常见的人类体验，但我们对它的容忍度各不相同。这是因为影响疼痛感知的因素，如生活经历、精神状态和基因，在个体之间是不同的。此外，当我们感知疼痛时，神经系统的不同部分被激活。这些神经包括将疼痛信号从身体传递到大脑的神经，控制心脏和肠道等器官功能的神经，以及控制皮质醇等有助于对抗压力的激素分泌的神经。在我们的初步研究中，我们通过在健康人的食道（食道）中吹一个气球来诱导疼痛，同时测量控制心脏的神经的活动。我们证明了减缓心脏跳动的迷走神经的活动在一些受试者中增加，在另一些受试者中减少。有趣的是，活动量增加的受试者通常比活动量减少的受试者更焦虑和担心。这些结果表明，在对疼痛的反应方式上存在两种截然不同的人群。我们现在想对更多的受试者进行研究，以确定这两种对疼痛的反应有多普遍，并确定个体的特定反应是否可随着时间的推移而重现。此外，我们想确定两种类型的个体对压力的激素反应（皮质醇水平）是否不同，以及他们的食道在酸损伤后变得敏感的程度是否也不同。最后，我们想要确定的是，患有由食道引起的慢性疼痛但无法确定病因的患者是否也表现出与健康受试者相同的两种类型的疼痛反应。我们还将确定对疼痛表现不同的个体是否因为与其他人有不同的基因而这样做。预期结果：我们预计这项研究将提高我们对为什么个体对疼痛的反应不同的理解，以及某些个体是否更容易患上慢性疼痛。对人类健康的预期益处：如果某些人患慢性疼痛的风险更大，那么可以根据导致这种风险增加的原因制定治疗策略，然后可以采取预防措施，保护这些人免受可能使他们易患慢性疼痛的环境影响。

Nature of proposed research: while pain is a common human experience, our tolerance to it varies. This is because factors that influence pain perception such as life experiences, mental state and our genes, differ between individuals. Furthermore, when we perceive pain different parts of the nervous system are activated. These include nerves that carry pain signals from the body to the brain, control organ function e.g. heart and gut, and those that control the secretion of hormones such as cortisol that help combat stress. In our preliminary studies, we induced pain by blowing up a balloon in the healthy human oeosphagus (gullet) while we measured the activity of nerves that control the heart. We demonstrated that the activity of the vagus nerve which slows down the heart increased in some subjects and decreased in others. Interestingly, subjects who showed an increase in activity were in general more anxious and worried than those who showed a decrease in activity. These results suggest that two distinct populations exist in the way they respond to pain. We now want to carry out studies in a larger number of subjects to determine how prevalent the two types of responses to pain are and also to determine whether a particular response in an individual is reproducible over time. Furthermore we want to determine whether the hormonal response (cortisol levels) to stress is different in the two types of individuals and whether they also differ in the degree to which their oesophagus becomes sensitive after injury with acid. Finally we want to determine if patients who have chronic pain arising from the oesophagus but in whom no cause can be identified also demonstrate the same two types of response to pain as healthy subjects. We will also determine whether individuals who behave differently to pain do so because they have different genes from others. Prospective outcomes: we anticipate that this research will improve our understanding of why individuals differ in their response to pain and also whether certain individuals are more likely to developing chronic pain conditions. Expected benefit to human health: if certain individuals are more at risk of developing chronic pain then treatment strategies can be developed based on the reasons leading to this increase in risk, and preventative measures can then be taken to protect these individuals from environmental influences that may predispose them to the development of chronic pain conditions.