Lower oesophageal sphincter hypersensitivity to opioid receptor stimulation in patients with idiopathic achalasia

Abstract

Impairment of non-cholinergic innervation of the lower oesophageal sphincter has been suggested in idiopathic achalasia. As opioid nerves are present in the lower oesophageal sphincter and opioid peptides affect lower oesophageal sphincter motility, the effect of an opioid agonist, morphine (100 μg/kg iv), and an opioid blocker, naloxone (80 μg/kg iv), on lower oesophageal sphincter motor function was assessed in 10 healthy subjects and in 10 patients with untreated idiopathic achalasia on separate days and in randomised order. In addition, in six of the patients, naloxone 0.8 mg iv was injected 60 minutes after morphine and recordings continued for a further five minutes. Lower oesophageal sphincter pressure was monitored by a sleeve device. In the healthy subjects morphine decreased (p < 0.01) resting lower oesophageal sphincter pressure by 4 (1) mm Hg (23 (8)%). In the achalasia patients the effect was more marked, lower oesophageal sphincter pressure being reduced (p < 0.01) by 11 (2) mm Hg (46 (8)%). Naloxone reversed lower oesophageal sphincter pressure to basal. Both absolute and percentage decreases after morphine were significantly greater (p < 0.05) in the achalasia patients than in the healthy subjects. Swallow induced lower oesophageal sphincter relaxation was significantly decreased (p < 0.05) by morphine in the healthy subjects but not in the achalasia patients. Naloxone had no effect on resting lower oesophageal sphincter pressure or swallow induced relaxation in either healthy subjects or achalasia patients. In conclusion achalasia patients are hypersensitive to the effect of morphine on resting lower oesophageal sphincter pressure. This finding is unlikely to be the result of a denervation process involving opioid nerves.