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 ,uggkg iv), and an opioid blocker, naloxone (80 ,ug/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 ofthe patients, naloxone 0x8 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<001) 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<005) in the achalasia patients than in the healthy subjects. Swallow induced lower oesophageal sphincter relaxation was significantly decreased (p<005) 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 ofa denervation process involving opioid nerves. (Gut 1993; 34: 16-20) Idiopathic achalasia is a disease ofthe oesophagus characterised by absent peristalsis, impaired lower oesophageal sphincter relaxation after swallows and often a high lower oesophageal sphincter resting pressure.' Achalasia is thought to be determined by a visceral neuropathy which probably involves the vagal preganglionic and the postganglionic nerve fibres of the oesophagus.2 During the past years the attention has been focused mainly on the lower oesophageal sphincter, and some results suggest that noncholinergic inhibitory nerves are impaired4 whereas cholinergic innervation is at least partly preserved.Opioid nerves have been shown in the myenteric plexus of normal lower oesophageal sphincter in man" and various opioid receptors have been identified in the opossum lower oesophageal sphincter, in the sphincter muscle and the nerve fibres surrounding it.'" Furthermore, evidence exists that opioid peptides affect lower oesophageal sphincter motor function."-'5 In particular one study'4 showed that an opioid agonist, morphine, administered to healthy subjects determined a decrease and an opioid blocker, naloxone, an increase, although modest, in lower oesophageal sphincter pressure. The latter finding may suggest that endogenous opioids contribute to th...

The effect of cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux was investigated in nine healthy subjects. All subjects were studied twice in a randomized order according to a common protocol: 30 min after completion of a 700-kcal meal they put their nondominant hand in water either at 37 degrees C (control stimulus) or at 4 degrees C (stressful stimulus) cyclically for 20 min. Pulse rate and blood pressure rose significantly (P less than 0.01) during the stressful stimulus, but remained unaffected by the control stimulus. Rate of transient lower esophageal sphincter relaxations/30 min [median (interquartile range)] was similar before and during control stimulus, 4 (2.7-5.0) and 3 (2.0-4.5), respectively, whereas it was markedly inhibited during the stressful stimulus [from 5 (3.7-6.0) to 2 (1.0-2.0); P less than 0.05 vs control stimulus]. Rate of reflux episodes/30 min was also similar before and during control stimulus, 1 (0-1.2) and 1 (1.0-2.2), but fell consistently during the stressful stimulus [from 2 (0-3.2) to 1 (0-2.0); P less than 0.05 vs control stimulus]. Percentage of transient lower esophageal sphincter relaxations accompanied by a reflux episode was unaffected by stress as was basal lower esophageal sphincter pressure. It is concluded that cold stress decreases the postprandial rate of transient lower esophageal sphincter relaxations and reflux episodes in healthy humans.

Our findings indicate that in patients with idiopathic achalasia oral administration of loperamide at a high dose markedly decreases resting LOS pressure. This may not occur through opioid receptor stimulation and requires intestinal absorption of the drug. The possible effect of combining a small dose of loperamide with the traditional achalasia drugs awaits further evaluation.

The effect of cold stress on esophageal peristalsis was assessed in nine healthy subjects after ingestion of a 700-kcal meal. All subjects underwent a control stimulus (immersion of the nondominant hand in water at 37" C) and a stressful stimulus (immersion in water at 4" C ) on separate days and in randomized order. When compared to the control stimulus, stress increased blood pressure ( p < 0.01) and pulse rate ( p < 0.05). It also determined an increase of 9 k 3 mm H g (mean & SEM) in amplitude ( p < 0.05), of 0.2 & 0.1 seconds in duration ( p < 0.11, and of 0.3 * 0.1 cm per second in propagation velocity ( p < 0.05) of peristalsis, as assessed after water swallows. Percentage of failed peristalsis was unaffected by stress. We conclude that cold stress exerts only minor effects on variables of the peristaltic waue and does not induce dysmotility in the esophagus of healthy subjects during the postprandial period. (Journal of Gastrointestinal Motility Key Words: 1 991 ; 3(3): 1 63-1 67) stress; esophageal function; esophagus.