以便秘和腹泻为主的肠易激综合征与5-羟色胺信号改变

Background &Aims: Evidence suggests that postprandial platelet-depleted plasma 5-hydroxytryptamine (5-HT) concentrations may be abnormal in irritable bowel syndrome (IBS). However, interpretation of the data has been hampered by the variable methodology and rather small numbers used in previous studies. Therefore, the aim of this study was to measure concentrations of platelet-depleted plasma 5-HT and its metabolite 5-HIAA under fasting and fed conditions in a large group of patients with diarrhea-predominant (d-) and constipation-predominant (c-) IBS, compared with controls. The ratio of plasma 5-HIAA:5-HT and platelet stores was also assessed. Methods: Twenty-nine c-IBS patients (aged, 19-53 years), 55 d-IBS patients (aged, 19-52 years), and 35 healthy volunteers (aged, 18-46 years) had platelet-depleted plasma 5-HT/5-HIAA concentrations measured using reverse-phase, high-performance liquid chromatography with fluorimetric detection before and after a standard meal. Results: d-IBS patients had raised platelet-depleted plasma 5-HT concentrations under fasting and fed conditions (P < .05). However, the postprandial relative to fasting concentration was similar to controls. In contrast, c-IBS patients failed to show an increase in platelet-depleted plasma 5-HT concentration with meal ingestion compared with controls (P < .01). c-IBS was associated with decreased 5-HIAA (P < .01) but normal 5-HIAA:5-HT ratio and d-IBS with normal 5-HIAA concentrations but reduced 5-HIAA:5-HT ratio (P < .005). c-IBS but not d-IBS patients had increased platelet 5-HT. Conclusions: These results support the concept that d-IBS is characterized by reduced 5-HT reuptake, whereas impaired release may be a feature of c-IBS. These results also provide a rational basis for current pharmacologic approaches involving modulation of different 5-HT receptors in c-and d-IBS.

肠易激综合征患者的内脏感觉神经通路超敏反应的新证据

Background &Aims: Visceral hypersensitivity in irritable bowel syndrome (IBS) patients has been documented by evaluation of perceived stimulations that can reflect abnormalities of both sensory neurocircuitry and cognitive processes. The presence of actual neurohypersensitivity in human beings has not been documented separately. Because subliminal stimulations are free from the influence of stimulus-related cognitive processes, functional magnetic resonance imaging (fMRI) cortical response to these stimuli can be considered a measure of activity of the neural circuitry alone. The aim of this study was to compare quantitatively the cerebral cortical fMRI activity response to equal subliminal stimulations between IBS patients and age-matched controls. Methods: We studied 10 IBS patients and 10 healthy controls using a computerized barostat-controlled rectal distention device. fMRI activity volume and percent maximum signal intensity change for equal subliminal distention pressures were compared between controls and patients. Results: Three levels of subliminal distention pressures (eg, 10, 15, and 20 mm Hg), were represented in both controls and patients and were analyzed for fMRI response. In all 3 distention levels the fMRI activity volume in IBS patients was significantly larger than age-and sex-matched controls (P < .05). The percent maximum signal intensity change was similar between IBS patients and controls. Conclusions: The volume of cerebral cortical activity response to equal subliminal distention pressures in IBS patients is significantly larger than in controls, documenting the existence of hypersensitivity of the neural circuitry in this patient group irrespective of stimulus-related cognitive processes.