As overlap between these functional syndromes comes to be accepted as a clinical reality, it has posed a dilemma for those who seek to develop precise clinical definitions for the individual functional disorders. For example, where does NERD end and functional dyspepsia begin?  This is far more than an issue of semantics; the inclusion of patients with predominant heartburn in a dyspepsia study population which examines the response to an acid-suppressing agent will significantly bias the study in a positive direction , ; as a corollary, the exclusion of heartburn, as advocated by some , will lessen the impact of the same agents. The approach to definition will similarly have a significant impact on studies of the epidemiology, pathophysiology and natural history of the respective disorders. The need to delineate succinct patient categories notwithstanding, the clinical reality is that many NERD patients complain of heartburn and dyspepsia; attempts to separate patients on the basis of the relative "predominance" of one or other symptom complex seems unrealistic, if not impossible. Other data supports the overlap between the disorders.
Firstly, the intimacy of physiological relationships between the lower esophagus and the upper stomach continues to be revealed. Thus, fundic distension is a primary mechanism of induction of transient lower esophageal relaxations (TLESR's) ; which are, in turn, responsible for most episodes of reflux in both health and in GERD . Secondly, similar disturbances in upper gut motility, including gastric emptying delay, have been described in NERD and functional dyspepsia . In functional dyspepsia, impaired fundic accommodation appears to be a prominent feature . Very recent data suggest that dysfunction of the upper stomach may occur in NERD also , . Just as the overlap with functional dyspepsia, and the potential role of motility and or sensory dysfunction in symptom generation, have been implicated to explain the relatively inferior response to proton pump inhibitors in NERD, these same factors have encouraged investigation of a potential role for prokinetic agents. To date there have been few studies of pro-kinetic agents in NERD; those that have been performed have not proven encouraging , , .
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