Visceral pain processing is abnormal in a majority of irritable bowel syndrome (IBS) patients. Aberrant endogenous nociceptive modulation and anticipation are possible underlying mechanisms investigated in the current study. Twelve IBS patients and 12 matched healthy controls underwent brain fMRI scanning during the following randomised stimuli: sham and painful rectal distensions by barostat without and with simultaneous activation of endogenous descending nociceptive inhibition using ice water immersion of the foot for heterotopic stimulation. Heterotopic stimulation decreased rectal pain scores from 3.7+/-0.2 to 3.1+/-0.3 (mean+/-SE, scale 0-5) in controls (p<0.01), but not significantly in IBS. Controls differed from IBS patients in showing significantly greater activation bilaterally in the anterior insula, SII and putamen during rectal stimulation alone compared to rectal plus heterotopic stimulation. Greater activation during rectal plus heterotopic versus rectal stimulation was seen bilaterally in SI and the right superior temporal gyrus in controls and in the right inferior lobule and bilaterally in the superior temporal gyrus in IBS. Rectal pain scores were similarly low during sham stimulation in both groups, but brain activation patterns differed. In conclusion, IBS patients showed dysfunctional endogenous inhibition of pain and concomitant aberrant activation of brain areas involved in pain processing and integration. Anticipation of rectal pain was associated with different brain activation patterns in IBS involving multiple interoceptive, homeostatic, associative and emotional areas, even though pain scores were similar during sham distension. The aberrant activation of endogenous pain inhibition appears to involve circuitry relating to anticipation as well as pain processing itself.

Background and aims: Melatonin, a sleep promoting agent, is involved in the regulation of gastrointestinal motility and sensation. We aimed to determine if melatonin was effective in improving bowel symptoms and sleep disturbances in irritable bowel syndrome (IBS) patients with sleep disturbance. Methods: Forty IBS patients (aged 20-64 years; 24 female) with sleep disturbances were randomly assigned to receive either melatonin 3 mg (n = 20) or matching placebo (n = 20) at bedtime for two weeks. Immediately before and after the treatment, subjects completed bowel, sleep, and psychological questionnaires, and underwent rectal manometry and overnight polysomnography. Results: Compared with placebo, melatonin taken for two weeks significantly decreased mean abdominal pain score (2.35 v 0.70; p,0.001) and increased mean rectal pain threshold (8.9 v 21.2 mm Hg; p,0.01). Bloating, stool type, stool frequency, and anxiety and depression scores did not significantly differ after treatment in both groups. Data from sleep questionnaires and polysomnography showed that the two week course of melatonin did not influence sleep parameters, including total sleep time, sleep latency, sleep efficiency, sleep onset latency, arousals, duration of stages 1-4, rapid eye movement (REM) sleep, and REM onset latency. Conclusions: Administration of melatonin 3 mg at bedtime for two weeks significantly attenuated abdominal pain and reduced rectal pain sensitivity without improvements in sleep disturbance or psychological distress. The findings suggest that the beneficial effects of melatonin on abdominal pain in IBS patients with sleep disturbances are independent of its action on sleep disturbances or psychological profiles.

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