The effect of acute serotonergic modulation on rectal motor function in diarrhea-predominant irritable bowel syndrome and healthy controls.
BACKGROUND
Irritable bowel syndrome (IBS) patients suffer from visceral hypersensitivity and show increased activity in the brain emotional arousal network following a rectal stimulus, compared with controls. Serotonergic activity can be decreased by acute tryptophan depletion (ATD), which increases visceral perception and also increases activity in the brain's emotional arousal network during rectal stimulation. Treatment with a serotonin reuptake inhibitor such as citalopram is effective in some IBS patients. Hence, serotonergic modulation alters visceral perception. However, it is not clear whether serotonergic modulation alters rectal motor function.


OBJECTIVE
The aims of the study were to evaluate the effect of the administration of ATD and citalopram on rectal motor function in diarrhea-predominant IBS (d-IBS) patients and controls using a barostat procedure.


METHODS
Following a randomized, double-blind placebo-controlled crossover design, an ATD and citalopram experiment was conducted. Fourteen d-IBS patients and 14 healthy, matched (age, sex, BMI) controls participated. Rectal volume (RV), adaptive relaxation (RAR), and compliance (RC) were determined using a barostat procedure.


RESULTS
d-IBS patients showed significantly decreased RV (P<0.04), RAR (P<0.03), and RC (P=0.05) compared with the controls. ATD and citalopram did not influence RV, RAR, or RC significantly (all P's>0.1).


CONCLUSIONS
d-IBS patients have disturbed rectal pressure-volume relations. Visceral perception in IBS is associated with both increased activity in the brain's emotional arousal network and decreased RC. Acutely decreasing or increasing serotonergic activity does not affect these characteristics in d-IBS patients or healthy controls. The pathophysiology in d-IBS contains both a rectal motor component and a central neuropsychologic component.
Department of Internal Medicine, Division of Gastroenterology, University Hospital Örebro, Örebro, Sweden. m.vannieuwenhoven@versatel.nl
Michiel A
MA
van Nieuwenhoven
Tessa O C
TO
Kilkens
D000328:Adult; D001143:Arousal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D015283:Citalopram / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects*; D009426:Netherlands; D017288:Pain Threshold / Q000187:drug effects; D011312:Pressure; D012007:Rectum / Q000294:innervation*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014364:Tryptophan / Q000172:deficiency*
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan