title: Acid reflux directly causes sleep disturbances in rat with chronic esophagitis.
abstract: OBJECTIVE
  Gastroesophageal 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.
  
  
  METHODS
  Acid 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.
  
  
  RESULTS
  Rats 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improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn.
  
  
  CONCLUSIONS
  Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakahara
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Shiba
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Japan; Molecular Sleep Biology Laboratory, International Institute for Integrative Sleep Medicine, World Premier International Research Center, Tsukuba University, Tsukuba, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004942:Esophagitis, Peptic / Q000150:complications* / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D004947:Esophagus / Q000473:pathology; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D012892:Sleep Deprivation / Q000150:complications / Q000503:physiopathology; D012894:Sleep Stages / Q000187:drug effects; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology
chemical_list: D054328:Proton Pump Inhibitors; D009853:Omeprazole