Receptors and transmission in the brain-gut axis: potential for novel therapies. I. Receptors on visceral afferents

Visceral afferents are the information superhighway from the gut to the central nervous system. These sensory nerves express a wide range of membrane receptors that can modulate their sensitivity. In this themes article, we concentrate on those receptors that enhance the excitability of visceral afferent neurons. Some receptors are part of a modality-specific transduction pathway involved in sensory signaling. Others, which are activated by substances derived from multiple cellular sources during ischemia, injury, or inflammation, act in a synergistic fashion to cause acute or chronic sensitization of the afferent nerves to mechanical and chemical stimuli. Such hypersensitivity is the hallmark of conditions such as irritable bowel syndrome. Accordingly, these receptors represent a rational target for drug treatments aimed at attenuating both the inappropriate visceral sensation and the aberrant reflex activity that are the foundation for alterations in bowel function.