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Neurogastroenterology/motility
Are functional constipation and constipation-subtype irritable bowel syndrome distinct with respect to 5-hydroxytryptamine signalling and motor-sensory function?
  1. C Shekhar *1,
  2. P Monaghan2,
  3. J Adaway2,
  4. J Morris3,
  5. P Whorwell1,
  6. B Keevil2,
  7. L A Houghton1,4
  1. 1Neurogastroenterology Unit, University of Manchester, Manchester, UK
  2. 2Biochemistry Department, UHSM, Manchester, UK
  3. 3Statistics, UHSM, Manchester, UK
  4. 4College of Medicine, Mayo Clinic, Florida, USA

Abstract

Introduction Recent studies suggest that patients identified by Rome III criteria for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) are not distinct groups. We have shown that patients with IBS-C exhibit limited 5-HT response to meal ingestion, with plasma concentrations remaining similar to fasting. Our aim was to determine whether patients with FC show a similar 5-HT meal response as IBS-C, and to investigate relationships to motor-sensory function.

Methods 23 IBS-C patients (aged 19–50 years; Rome III), 11 FC patients (25–46 years; Rome III) and 23 healthy volunteers (HV) (20–49 years) were recruited. Plasma 5-HT concentrations were measured under fasting (2 h) and fed (4 h) conditions. Within 2 weeks, oro-caecal (hydrogen breath) and colonic (radio-opaque markers followed by X-ray) transit, along with rectal sensitivity (barostat) were determined.

Results FC and IBS-C had similarly reduced 5-HT responses to meal ingestion (mean increase from fasting (SD), FC: −1.1 nmol/l (±6.9), p=0.1; IBS-C: −1.9 nmol/l (±7.0), p=0.02) compared with HV (+ 4.7 nmol/l (±9.6)), but comparable fasting 5-HT concentrations (FC: 34.2 nmol/l (±13.2); IBS-C: 27.8 nmol/l (±17.3); HV: 27.0 nmol/l (±9.6)). Likewise, FC and IBS-C have reduced colonic (FC: 61.6 h (±17.9), p=0.001; IBS-C: 55.6 h (±18.5), p=0.001 vs HV: 34.6 h (±17.8)) but not orocecal ((FC: 321.4 min (±96.6); IBS-C: 311.7 min (±96.6) vs HV: 301.8 min (±87.5)) transit compared with HV. Only rectal sensitivity differed, with IBS-C exhibiting lower pain thresholds (23.4 mm Hg (±8.3), p=0.03) but not FC (32.7 mm Hg (±12.2) compared with HV (30.7 mm Hg (±8.2)). Moreover, although the 5-HT meal response was similar between hyper- (−0.7 nmol/l (±4.9)), normo- (−1.5 nmol/l (±7.5) and hypo- (−4.7 nmol/l (±7.8)) sensitive constipated patients, those with hypo-sensitivity (FC (27%) and IBS-C (4%)) had higher fasting and fed 5-HT concentrations (fasting: 44.3 nmol/l (±17.2), fed: 39.6 nmol/l (±20.8), p=0.001 and p=0.08, respectively) compared with HV (24.7 nmol/l (±7.5), 27.9 nmol/l (±9.5)). Hyper- (20.4 nmol/l (±7.6), 19.7 nmol/l (±5.6)) and normo- (30.7 nmol/l (±16.6), 29.2 nmol/l (±16.8)) sensitive patients were no different from HV.

Conclusion There appears to be no distinction between FC and IBS-C patients with respect to 5-HT meal response and GI transit, although IBS-C patients are more viscerally sensitivity. Hypo-sensitive constipated patients appear to have a distinct 5-HT profile.

  • 5 HT
  • Constipation
  • Functional Gastrointestinal Disorders (FGID)
  • IBS
  • Rectal Sensitivity
  • ROME III

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Footnotes

  • Competing interests None.

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