Epithelial-Neuronal Communication in the Colon: Implications for Visceral Pain

Visceral hypersensitivity and pain result, at least in part, from increased excitability of primary afferents that innervate the colon. In addition to intrinsic changes in these neurons, emerging evidence indicates that changes in lining epithelial cells may also contribute to increased excitability. Here we review recent studies on how colon epithelial cells communicate directly with colon afferents. Specifically, anatomical studies revealed specialized synaptic connections between epithelial cells and nerve fibers and studies using optogenetic activation of the epithelium showed initiation of pain-like responses. We review the possible mechanisms of epithelial-neuronal communication and provide an overview of the possible neurotransmitters and receptors involved. Understanding the biology of this interface and how it changes in pathological conditions may provide new treatments for visceral pain conditions.