Effect of pharmacological modulation of the autonomic nervous system on human oesophageal pain hypersensitivity

腹痛是多种胃肠道疾病患者常见且重要的症状。其中一些没有明显的潜在结构原因，因此被称为“功能性”。这种越来越被认可的功能性胃肠疾病（FGID）现在已知至少部分是由于肠道对化学物质和机械拉伸等刺激的敏感性增加而发生的（称为内脏疼痛过敏：VPH）。我们通过实验将酸引入健康志愿者的食道（食道），建立了一种有效的人体VPH模型。这个模型使我们能够研究为什么有些人对酸比其他人更敏感。我们最近表明，影响这种反应的一个重要因素是神经系统中被称为自主神经系统（ANS）的一部分的活动。ANS控制许多不自主的功能，如心率和血压，它有两个主要部分（称为交感神经和副交感神经）。根据这些部分的相对活性不同，不同个体对酸的反应也不同。我们希望进一步探索导致这一观察结果的确切机制，并证明用药物改变这两种ANS活性可能会影响模型中VPH的程度。这有可能导致现有药物的新用途，特别是在FGID患者中，但也可能在一般的慢性疼痛管理领域。

Abdominal pain is a very common and important symptom reported by patients with a variety of gastrointestinal diseases. Some of these have no evident underlying structural cause and are thus called ?functional?. Such increasingly recognized functional gastrointestinal disorders (FGID) are now known to at least in part occur because of increased gut sensitivity to stimuli such as chemicals and mechanical stretching (called visceral pain hypersensitivity: VPH). We have developed a well-validated human model of VPH by experimentally introducing acid into the oesophagus (gullet) of healthy volunteers. This model has allowed us to study why some people sensitize more to acid than others. We have recently shown that one important factor affecting this response is the activity of a part of the nervous system called the autonomic nervous system (ANS). The ANS controls many involuntary functions such as heart rate and blood pressure and has two main parts (called the sympathetic and parasympathetic). Depending on the relative activities of these parts different individuals show different responses to acid. We wish to further explore the exact mechanisms that lead to this observation and also prove the concept that altering these 2 ANS activities with drugs could affect the degree of VPH in the model. This has potential to lead to new uses of existing drugs particularly in patients with FGID, but also perhaps in the field of chronic pain management in general.