Neuromuscular function of the human lower oesophageal sphincter in reflux disease and Barrett's oesophagus

Background-Columnar lined (Barrett's) oesophagus is often considered a sequ el to chronic severe reflux disease. Aberrant lower oesophageal sphincter ( LOS) motility associated with Barrett's oesophagus includes reduced basal L OS pressures. The aim of this study was to characterise neuromuscular funct ion of the LOS in normal (squamous cell carcinoma (SCC) with uninvolved LOS ) and reflux affected (Barrett's) oesophagus in vitro. Methods-Strips of LOS muscle were prepared at biopsy following oesophagecto my from 16 patients with SCC and seven patients with oesophageal adenocarci noma and Barrett's oesophagus associated with a history of reflux disease. LOS smooth muscle responses were recorded in response to electrical field s timulation (EFS), potassium chloride (KC1), DMPP, isoprenaline, capsaicin, bethanechol, and tachykinins. Results-Basal LOS tone and LOS relaxations in response to isoprenaline, EFS , and DMPP were not significantly altered in the Barrett's group. After tet rodotoxin pretreatment, responses to KCL and DMPP were significantly reduce d in the SCC but not in Barrett's LOS. Maximal contraction in response to b ethanechol was significantly decreased in Barrett's LOS while substance P a nd NK-2 receptor mediated contraction was unaltered. Capsaicin, NK-1, and N K-3 receptor agonists exerted negligible effects on LOS tone. Conclusions-LOS muscle strips from patients with reflux associated Barrett' s oesophagus exhibit a reduction in cholinergic muscle contraction while re taining similar features of basal tone, responses to tachykinins, and inhib itory muscle and neural function. Enteric inhibitory neurones in LOS muscle strips from patients with reflux associated Barrett's oesophagus display r esistance to axonal sodium channel blockade. No evidence for functional NK- 1 or NK-3 receptors or capsaicin sensitive axon collateral reflexes was obs erved in the human LOS.