AIM: To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome (IBS).Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function.METHODS: Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities (visual analogue scale, VAS 0-100) during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously (heterotopic stimulation) were recorded in 40 female patients with IBS and 20 female healthy controls.RESULTS: Rectal hypersensitivity (defined by 95% CI of controls) was seen in 21 (53%), somatic hypersensitivity in 22 (55%) and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 (-11 to -1) in controls, but increased rectal pain by 2 (-3 to +6) in all IBS patients (P＜0.05) and by 8 (-2 to +19) in IBS patients with somatic and visceral hypersensitivity (P＜0.02).CONCLUSION: A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.