How does inflammation of the gut change its sensory innervation?

大量因肠道疼痛和不适而被转诊至胃肠科医生的患者得不到有效的治疗。这对生活质量有很大影响，通常涉及侵入性测试，以排除炎症或癌症原因。这些患者被归类为肠易激综合征(IBS)。患有结肠镜检查阳性的可诊断炎症性肠病(IBD)的患者可能会出现类似的症状，但也不能治疗这种症状。越来越明显的是，IBS患者中有一大部分人曾经历过感染或炎症，事实上，他们肠道活检中的细胞类型也发生了变化。因此，IBS和炎症有共同的特点。这可能为我们寻找治疗IBS和IBD症状的新方法提供一种手段。小鼠实验性炎症后结肠的微观变化与人类相似，所以我们可以从这个模型中发现更多。我们最近证实，小鼠结肠和直肠有几种类型的感觉神经纤维，它们传递收缩、扩张和化学介质从组织释放到中枢神经系统的信息。几乎可以肯定，这些都是导致患者出现症状的原因。在这个项目中，我们的目标是发现在实验性炎症中，这些感觉神经对机械和化学刺激的反应是如何变化的。重要的是，我们将研究组织中存在的可能激活感觉神经的介质和--或者可能增加的感觉神经上的受体。我们希望这些实验将提供一个靶点，针对IBS和IBD症状的新药物治疗。

A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.