Abstract

Recent studies suggest that patients identified by the Rome III criteria for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) are not distinct groups (1). We have shown that patients with IBS-C exhibit no or limited 5-HT response to meal ingestion, with plasma concentrations remaining similar to those under fasting conditions (2). The aim of this study was to determine whether patients with FC show a similar 5-HT response to meal ingestion as patients with IBS-C, and to investigate any relationship to gastrointestinal transit and visceral sensitivity. Methods: 23 female IBS-C patients (aged 1950yrs;Rome III), 11 female FC patients (25-46yrs;Rome III) and 23 healthy female volunteers (HV) (20-49yrs) were recruited. Platelet depleted plasma 5-HT concentrations were measured under fasting (2hrs) and fed (4hrs) conditions. Within 2 weeks, oro-caecal (hydrogen breath test) and colonic (radio-opaque markers followed by X-ray) transit, along with rectal sensitivity (barostat) were determined. 5-HT concentration was assessed using rapid liquid chromatography tandem mass spectrometry (3). Results: Both patients with FC and IBS-C had similarly reduced 5-HT responses to meal ingestion (mean increase from fasting (SD), FC:-1.1nmol/l(±6.9),p=0.1; IBS-C:-1.9 nmol/l(±7.0),p=0.02) compared with HV (4.7nmol/ l(±9.6)), but comparable fasting baseline 5-HT concentrations (FC:34.2nmol/l(±13.2); IBSC: 27.8nmol/l(±17.3); HV:27.0nmol/l(±9.6)). Likewise, both FC and IBS-C patients had similarly reduced colonic (FC:61.6hrs(±17.9),p=0.001; IBS-C:55.6hrs(±18.5),p=0.001 v HV:34.6hrs(±17.8)) but not orocecal ((FC:321.4min(±96.6); IBS-C:311.7min(±96.6) v HV:301.8min(±87.5)) transit compared with HV. Only rectal sensitivity differed between groups, with IBS-C exhibiting lower pain thresholds (23.4mmHg (±8.3), p=0.03) but not FC (32.7mmHg(±12.2) comparedwithHV (30.7mmHg(±8.2)). Further examination revealed that although the 5-HTmeal response was similar between hyper(-0.7nmol/l(±4.9)), normo(-1.5nmol/l(±7.5)) and hypo(-4.7nmol/l(±7.8)) sensitive constipated patients, those with hypo-sensitivity (FC(27%) and IBS-C(4%)) had higher baseline fasting and fed 5-HT concentrations (fasting: 44.3nmol/l(±17.2), fed: 39.6nmol/l(±20.8), p=0.001p105:2228-2234, (2) Gastroenterol 2006;130:34-43, (3) J Chromatogr B 2009;877:2163±

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