D Keszthelyi1,2, F J Troost1,2, D M Jonkers1,2, H M van Eijk3, J Dekker1, W A Buurman4, A A M Masclee1,2. 1. Top Institute Food and Nutrition, Wageningen, The Netherlands. 2. Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands. 3. Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands. 4. School for Mental Health and Neuroscience, Division Neuroscience, Maastricht University Medical Centre+, Maastricht, The Netherlands.
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.
RCT Entities:
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 IBSpatients 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; IBSpatients exhibit lowered pain thresholds in both placebo and 5-HTP conditions. 5-HTP induces rectal hyperalgesia in hypersensitive but not in non-hypersensitiveIBSpatients. 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 IBSpatients. 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 hypersensitiveIBSpatients. 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 hypersensitiveIBSpatients and to a lesser magnitude in a significant number of healthy controls but in none of the non-hypersensitiveIBSpatients.
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