title: Visceral hypersensitivity in irritable bowel syndrome: evidence for involvement of serotonin metabolism--a preliminary study.
abstract: BACKGROUND
  Altered serotonergic (5-HT) metabolism and visceral perception have been associated with the pathogenesis of irritable bowel syndrome (IBS). Aim of this preliminary study was to assess the effect of the direct precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on systemic 5-HT metabolites and visceral perception and to assess potential differential responses between IBS and controls.
  
  
  METHODS
  15 IBS patients and 15 healthy volunteers participated in this randomized double-blind placebo controlled study. Visceroperception was measured by rectal barostat. The 100 mg 5-HTP or placebo was ingested orally. Serotonergic metabolites were assessed in platelet poor plasma.
  
  
  RESULTS
  5-HTP induces rectal allodynia in a significant number of healthy controls; IBS patients exhibit lowered pain thresholds in both placebo and 5-HTP conditions. 5-HTP induces rectal hyperalgesia in hypersensitive but not in non-hypersensitive IBS patients. Administration of 5-HTP significantly increased plasma 5-HTP levels (p < 0.001), did not affect 5-HT levels (p > 0.05), while levels of the main metabolite of 5-HT, 5-hydroxyindoleacetic acid, increased significantly (p < 0.05) in both groups. The magnitude of these changes observed in 5-HT metabolites was significantly greater in IBS patients.
  
  
  CONCLUSIONS
  Oral administration of 5-HTP induced significant alterations in systemic 5-HT metabolites that were accompanied by increased visceroperception of pain in controls and hypersensitive IBS patients. Changes in 5-HT metabolism appear to be important factors involved in visceral hypersensitivity as the 5-HTP-induced pro-nociceptive response was observed in all hypersensitive IBS patients and to a lesser magnitude in a significant number of healthy controls but in none of the non-hypersensitive IBS patients.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.|Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Keszthelyi
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.|Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: Troost
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.|Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: Jonkers
authors.affiliation: Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van Eijk
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Dekker
authors.affiliation: School for Mental Health and Neuroscience, Division Neuroscience, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.|Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: A A M
authors.initials: AA
authors.lastname: Masclee
mesh_terms: D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D055698:Touch Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D012701:Serotonin; D006916:5-Hydroxytryptophan
keywords: irritable bowel syndrome; rectal distension; serotonin; visceral hypersensitivity; visceral perception