Mechanosensitive afferent nerves and gastrointestinal motility

这个项目旨在从肠道中识别引起饱腹感、恶心或疼痛等感觉的不同类型的感觉神经。这些感觉神经还会激活重要的反射，协调肠道的不同区域，以确保食物得到适当的消化和推进。许多研究已经检查了这些感觉神经，以及它们如何通过拉伸肠壁来激活，但非常基本的问题仍有待回答。我们不知道有多少种不同类型的感觉神经，也不知道它们是否都以同样的方式对拉伸做出反应。我们无法在肠壁中辨认出它们的特殊结局。虽然这些感觉神经肯定会对拉伸做出反应，但众所周知，它们也会对肠壁的收缩做出反应。尽管如此，我们不明白肠壁的正常运动是如何激活它们的，也不知道为什么一些运动会导致疼痛。大多数实验将在取自人类杀死的豚鼠的小组织上进行，并在高度受控的条件下在器官浴中进行研究。其余的研究将在手术中获得的人类肠道组织样本上进行。这个项目将使用新的技术来记录肠壁拉伸和收缩过程中的感觉神经，以了解是什么激活了它们。此外，它们的末端将被贴上染料的标签，以揭示它们不同的形状。使用计算机化的成像技术，我们将识别它们是否对肠壁中的特定运动模式做出反应。最后，我们将记录人类结肠活标本中的这些感觉神经元，看看人类中是否存在与小动物相同类型的感觉神经。这项研究将首次全面描述肠壁上对扩张做出反应的感觉神经，包括那些激活疼痛通路的感觉神经。这是设计新药的先决条件，这些新药将以最小的副作用针对这些神经细胞。

This project aims to identify the different types of sensory nerves from the gut which cause sensations such as fullness, nausea or pain. These sensory nerves also activate important reflexes that coordinate different regions of the gut to ensure that food is properly digested and propelled. Many studies have examined these sensory nerves and how they can be activated by stretching the gut wall, but very basic questions remain to be answered. We do not know how many different types of sensory nerves there are and whether they all respond to stretch in the same way. We cannot identify their specialised endings in the wall of the gut. While these sensory nerves definitely respond to stretch, they are also known to respond to contractions of the gut wall. Despite this, we do not understand how the normal movements of the gut wall activate them, nor why some movements can lead to pain. Most of the experiments will be carried out on small pieces of tissue taken from humanely killed guinea pigs and studied, under highly controlled conditions, in organ baths. The remainder of the study will be on specimens of human gut tissue obtained at surgery. This project will use new techniques to record sensory nerves during both stretch and contraction of the gut wall to understand what activates them. In addition, their endings will be labelled with dye to reveal their different shapes. Using computerised imaging techniques we will identify whether they respond to particular patterns of movement in the gut wall. Lastly we will record from these sensory neurones in live specimens of human colon to see whether the same types of sensory nerves are present in humans as in the small animals. This study will provide the first comprehensive account of sensory nerves to the gut wall that respond to distension, including those that activate pain pathways. This is a pre-requisite for designing new drugs that will target these nerve cells with minimal side effects.