Central processing of visceral sensory signals

The ‘brain-gut axis’, conceptualized as the bidirectional neurohumoral signaling system connecting the gastrointestinal tract with the central nervous system, is part of an integrated interoceptive system which is continuously signaling homeostatic information about the physiological condition of the body to the brain. At brain level, this homeostatic-interoceptive information is integrated with exteroceptive signals, input from the reward system (assessing the motivational/hedonic value of stimuli) and affective & cognitive brain circuits. Dysfunction of gut-brain signaling plays a major role in the generation of unexplained visceral pain as well as food intake disorders. In health, food digestion and absorption remains largely unperceived; only the small fraction of interoceptive gut-brain signals that requires a behavioural response (pain, hunger) reaches consciousness. Profound changes in gut-brain signaling, most notably plasma levels of (an)orexigenic gut peptides, follow the cycles of hunger and food intake. Together with neural pathways signaling gastric distension and digestion of nutrients, these are critical players in homeostatic gut-brain signaling controlling feeding behaviour. Abnormalities in these mechanisms, including inappropriate peripheral signaling and dysfunction of homeostatic (hypothalamus, brainstem, insula), reward (ventral tegmentum, striatum) or affective & cognitive [amygdala, prefrontal cortex (PFC) and anterior cingulate cortex (ACC)] circuits in the brain, may result in dysregulation of food intake. Similarly, visceral pain results from the conscious perception of gut-brain signaling induced by noxious stimuli. At brain level, visceral pain-related interoceptive signals are processed in homeostatic centers and integrated with and modulated by signals from reward, affective and cognitive neurocircuits. The latter project in a ‘top-down’ fashion to brainstem areas such as the periaqueductal gray, which in turn send descending projections to the dorsal horn of the spinal cord, where pain transmission is modulated (descending modulatory system). Dysfunction of this system may cause physiological (non-noxious) stimuli to be perceived as painful (hypersensitivity), leading to chronic visceral pain.