title: Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity.
abstract: OBJECTIVE
  Autonomic nervous system dysfunction has been implicated in visceral hypersensitivity. However, the specific contribution of the parasympathetic nervous system (PNS) is unclear. We aimed to determine whether physiological and pharmacological manipulation of parasympathetic tone influences the development of hypersensitivity in a validated model of acid-induced oesophageal pain.
  
  
  METHODS
  Prior to, and following, a 30-min distal oesophageal infusion of 0.15 M hydrochloric acid, pain thresholds to electrical stimulation were determined in the proximal non-acid exposed oesophagus in healthy subjects. Validated sympathetic (skin conductance response) and parasympathetic (cardiac vagal tone) parameters were measured at baseline and continuously thereafter. In study 1, 55 subjects were randomised in a pragmatic blinded crossover design to receive deep breathing or un-paced breathing during acid infusion. In study 2, 32 subjects were randomised in a blinded, crossover design to receive intravenous atropine or placebo (saline) with deep breathing during acid infusion.
  
  
  RESULTS
  Study 1: Deep breathing increased cardiac vagal tone (2.1±2.3 vs -0.3±2.3, p=0.0006) with concomitant withdrawal of skin conductance response (-0.6±4.9 vs 3±4.8, p=0.03) in comparison with un-paced breathing. Deep breathing prevented the development of acid-induced oesophageal hypersensitivity in comparison with sham breathing (p=0.0001). Study 2: Atropine, in comparison with placebo, blocked the attenuating effect of deep breathing on the development of acid-induced oesophageal hypersensitivity (p=0.046).
  
  
  CONCLUSIONS
  The development of oesophageal hyperalgesia is prevented by physiologically increasing parasympathetic tone. This effect is pharmacologically blocked with atropine, providing evidence that the PNS influences the development of oesophageal pain hypersensitivity.
authors.affiliation: Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: Claude
authors.initials: C
authors.lastname: Botha
authors.affiliation: Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Farmer
authors.affiliation: Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Matias
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Brock
authors.affiliation: Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Gavrila
authors.affiliation: Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
authors.affiliation: Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Knowles
authors.affiliation: Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: Qasim
authors.initials: Q
authors.lastname: Aziz
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004947:Esophagus; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D010275:Parasympathetic Nervous System / Q000502:physiology*; D012119:Respiration; D055815:Young Adult
keywords: Abdominal Pain; Visceral Hypersensitivity; Visceral Nociception; Visceral Sensitivity