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

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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.