New insights in the pathophysiology of primary motility disorders of the esophagus.

Primary esophageal motility disorders (i.e. achalasia, diffuse spasm and related conditions) but also gastroesophageal reflux disease are characterised by a more or less pronounced dysfunction of esophageal body peristalsis and gastroesophageal sphincter relaxation. A normal interplay between inhibitory and excitatory peripheral nerves in the smooth muscle part of the esophagus is essential for the generation of esophageal peristalsis. The inhibitory nerve pathway determines the timing of the contraction; its neurotransmitter is NO. The excitatory pathway mainly determines the strength of the contraction; the neurotransmitter is acetylcholine. We have recently developed a technique to visualize the effect of the inhibitory nerves in the human tubular esophagus as a manometric relaxation of an artificial high pressure zone. We used this technique in patients with achalasia, diffuse spasm and related conditions and found an inverse relationship between percent inhibition and progression velocity of the contractions. We have examined with the same technique patients with reflux disease and found in these patients that the occurrence of acid reflux during TLESR's is accompanied by inhibition of the esophagus, whereas in normal controls it is accompanied by excitation. From a pathogenetic viewpoint we conclude as follows. Disorders of the inhibitory nerve pathway result in achalasia, diffuse spasm or related condition. We do not know exactly what happens when the excitatory pathway is diseased; there are arguments that these patients may have reflux disease.