Background: In this set of fMRI studies, our goal was to establish experimental pain paradigms to address emotional and cognitive modulation of the behavioural as well as neural response to visceral pain. Method: The blood oxygen level-dependent (BOLD) response to painful rectal distensions was assessed at baseline, in a negative emotional context induced by psychological stress (emotional modulation study: carried out in 15 female IBS patients and 12 healthy women) and in a visceral placebo analgesia paradigm (cognitive modulation study: carried out in 36 healthy subjects). For visceral placebo analgesia, a deceptive study paradigm was used in which expectation of analgesia was manipulated by giving subjects different instructions regarding an intravenous infusion of either "a highly potent analgesic drug" or "an inert substance", when in reality all subjects received a placebo (saline) during painful rectal distensions. Results: Distensions delivered in a negative emotional context increased distension-induced discomfort and urge to defecate in IBS patients but not controls. At the same time, IBS patients demonstrated more pronounced stress-induced modulation of neural activation during rectal stimulation in the insula, midcingulate cortex, and ventrolateral prefrontal cortex. The placebo analgesia paradigm, carried out in healthy subjects, revealed that manipulation of expectation resulted in significantly decreased subjective pain ratings. Placebo responders demonstrated significantly greater activation of the dorsolateral prefrontal cortex during expectation of analgesia compared to non-responders. Discussion: Pain amplification and hypervigilance in IBS may be related to altered affective-cognitive modulation of the pain response.