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.

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