Recent advances in brain science have shown that visceral pain is the representative interoceptive signal. Visceral pain arose early in the evolutionary history of animals. Bottom-up processing from gut-to-brain and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling constitute a circuit. Irritable bowel syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal discomfort associated with bowel dysfunction. Brain imaging techniques have enabled us to depict the visceral pain pathway as well as the related emotional circuit. To test visceral perception and perception-evoked emotion, we use a barostat bag in the colorectum. In humans, radioactive H₂[¹⁵O] saline was then injected at bag inflation and regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET). Receptor ligand PET using [¹¹C]-doxepin for histamine H₁ receptor or [¹¹C]-raclopride for dopamine D₂ receptor was also performed. The other methods for brain imaging are functional magnetic resonance imaging (fMRI), topographic mapping of the electroencepharography (EEG), viscero-sensory evoked potential (VEP) and auditory brain stem response (ABR). In animals, visceromotor response (VMR), microdialysis, and immunohistochemistry of the brain were examined. IBS is also thought to be a disorder of the brain-gut link associated with an exaggerated response to stress. Corticotropin-releasing hormone (CRH), a major mediator of the stress response in the brain-gut axis, is an obvious candidate in the pathophysiology of IBS. Indeed, administration of CRH has been shown to aggravate the visceral sensorimotor response in IBS patients and the administration of peptidergic CRH antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another likely candidate associated with brain-gut function in IBS since 5-HT₃ antagonists, 5-HT₄ agonists, and antidepressants were demonstrated to regulate 5-HT neurotransmission in IBS patients. Autonomic nervous system function, the neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS patients. Further studies on stress and visceral pain neuropathways in IBS patients are warranted.