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Extrinsic primary afferent signalling in the gut

Nature Reviews Gastroenterology & Hepatology volume 10, pages 286–296 (2013)Cite this article

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Abstract

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that just five structurally distinct types of sensory endings are present in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular–mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators. Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.

Key Points

  • The gut is innervated by several classes of extrinsic sensory neurons that have distinct combinations of properties making them sensitive to particular mechanical and chemical stimuli

  • Progress has been made in identifying the morphology of sensory endings in the gut wall, possibly providing a more robust means to classify sensory innervation

  • Five different morphological types of endings can be distinguished by their structure; these account for the great majority of sensory nerves to the gastrointestinal tract and seem to correspond to distinct major physiological classes

  • The physiological properties of extrinsic afferent nerves innervating the gut are characterized by variability and by plasticity, which can make it difficult to reliably distinguish the classes of sensory neurons that underlie gut sensation

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Figure 1: Five morphological types of extrinsic sensory neurons to the gut.

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  1. Centre for Neuroscience and Discipline of Human Physiology, Flinders Medical Science and Technology, Flinders University, Sturt Road, Bedford Park, 5042, SA, Australia

    Simon J. H. Brookes, Nick J. Spencer, Marcello Costa & Vladimir P. Zagorodnyuk

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Brookes, S., Spencer, N., Costa, M. et al. Extrinsic primary afferent signalling in the gut. Nat Rev Gastroenterol Hepatol 10, 286–296 (2013). https://doi.org/10.1038/nrgastro.2013.29

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