Esophageal afferent innervation and its role in gastro-esophageal reflux disease symptoms

Despite the wide prevalence of gastro-esophageal reflux disease (GERD), the neurophysiological mechanisms underlying heartburn perception in the esophagus of patients with GERD remains incompletely understood. Recent studies have highlighted the potential influence sensory afferent nerves innervating the oesophageal epithelium may have on heartburn pathogenesis. The purpose of this review is to consider the current understanding of esophageal afferent neuronal innervation, including the nociceptive role of acid-sensing receptors expressed on these sensory nerves, in relation to pain perception in the esophagus of GERD patients.Central and peripheral pathways of sensitization following noxious stimulation of nociceptive receptors expressed on afferent nerves can regulate the strength of sensory nerve activation in the esophagus, which can result in the amplification or suppression of afferent signal transmission. The localization and characterization of mucosal sensory afferent nerves vary between GERD phenotypes and may explain the heterogeneity of symptom perception in patients with apparently similar levels of reflux.In this review, we discuss the relevance of afferent esophageal innervation in heartburn perception, with a particular focus on the pathways of reflux-induced activation of nociceptive nerves.