Visceral hypersensitivity in irritable bowel syndrome: evidence for involvement of serotonin metabolism--a preliminary study

Neurogastroenterol Motil. 2015 Aug;27(8):1127-37. doi: 10.1111/nmo.12600. Epub 2015 May 31.

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.

Key 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 & inferences: 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.

Keywords: irritable bowel syndrome; rectal distension; serotonin; visceral hypersensitivity; visceral perception.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / administration & dosage
  • 5-Hydroxytryptophan / metabolism*
  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Female
  • Humans
  • Hyperalgesia / chemically induced
  • Hyperalgesia / complications
  • Hyperalgesia / metabolism*
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / psychology
  • Male
  • Middle Aged
  • Pain Perception / drug effects
  • Pain Perception / physiology
  • Pain Threshold / drug effects
  • Serotonin / metabolism*
  • Touch Perception / drug effects
  • Touch Perception / physiology

Substances

  • Serotonin
  • 5-Hydroxytryptophan