Visceral hypersensitivity in non-erosive reflux disease

Non-erosive reflux disease (NERD) is defined as the presence of classic symptoms of gastro-oesophageal reflux disease (GORD) in the absence of oesophageal mucosal injury (or Barrett’s oesophagus) as determined by inspection at upper gastrointestinal endoscopy.1 As such it is regarded as being one of the two main phenotypes of GORD, the other being erosive oesophagitis (EO) where ulceration or erosions are evident. GORD is common, with estimates of 20–44% of Western populations having symptoms of GORD at least once a month and 20% weekly.2 The proportion of such patients with NERD is estimated to be between 503 and 70%.4 It is acknowledged that responses to standard acid suppressive treatments are 20–30% lower in patients with NERD than those with EO.5 Considering this, and the high prevalence of NERD, which is likely to increase in parallel with societal body mass index,6 the pathophysiological understanding of this condition remains a priority. The concept of visceral hypersensitivity (VH) is now well established in a variety of overtly inflammatory as well as functional gastrointestinal conditions.7 ,8 This review introduces the molecular and physiological basis of VH, particularly in respect of acid-sensing receptors, and presents the evidence that VH plays an important role in the pathophysiology of NERD. Within the spectrum of GORD, the pathophysiological relationship of EO and NERD remains the subject of debate.9 The classical and perhaps intuitive view that NERD is a mild form of GORD that might progress with time to EO is supported by some physiological, anatomical and histopathological findings. For instance, whilst demonstration of acid exposure is not a requirement for the definition of EO or NERD, there are studies that demonstrate that acid exposure as determined by 24 h pH studies is abnormal in only 45% of NERD patients …