Abstract
Background & AimsGastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis.MethodsAcid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily.ResultsRats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn.ConclusionsAcid reflux directly causes sleep disturbances in rats with chronic esophagitis.
Highlights
Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus [1], and it is characterized by typical symptoms such as heartburn and acid regurgitation [2]
Recent studies suggest that the association between GERD and sleep disturbances is bidirectional [10,14]; GERD causes sleep problems such as difficulty in falling asleep, frequent awakenings because of nighttime heartburn, early morning awakenings, and poor sleep quality [15]
The concepts that a nighttime reflux event precedes the arousal response [17] and that acid reflux is caused by a transient lower esophageal sphincter relaxation (TLESR) triggered by the awakening [18] remain somewhat controversial
Summary
Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus [1], and it is characterized by typical symptoms such as heartburn and acid regurgitation [2]. Sleep deprivation appears to cause worsening of the symptoms of GERD by promoting esophageal mucosal hypersensitivity against gastric acids [16]. Several factors are attributable for the association between GERD and sleep disturbances, nighttime reflux is the key factor. Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis
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