Abstract
Chronic disturbances of gastrointestinal function encompass a wide spectrum of clinical disorders that range from common conditions with mild-to-moderate symptoms to rare diseases characterized by a severe impairment of digestive function, including chronic pain, vomiting, bloating and severe constipation. Patients at the clinically severe end of the spectrum can have profound changes in gut transit and motility. In a subset of these patients, histopathological analyses have revealed abnormalities of the gut innervation, including the enteric nervous system, termed enteric neuropathies. This Review discusses advances in the diagnosis and management of the main clinical entities—achalasia, gastroparesis, intestinal pseudo-obstruction and chronic constipation—that result from enteric neuropathies, including both primary and secondary forms. We focus on the various evident neuropathologies (degenerative and inflammatory) of these disorders and, where possible, present the specific implications of histological diagnosis to contemporary treatment. This knowledge could enable the future development of novel targeted therapeutic approaches.
Key Points
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A wide spectrum of clinical phenotypes are characterized by degrees of gut sensorimotor dysfunction; at the clinically severe end, patients can have profound changes of gut transit and motility, with or without chronic visceral dilatation
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When histologically studied (and accepting some methodological limitations), a subset of patients with demonstrable gastrointestinal motor disturbances have evidence of disease to nerves of the enteric nervous system termed enteric neuropathies
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Several disorders, for example, oesophageal achalasia, gastroparesis, enteric dysmotility, intestinal pseudo-obstruction and chronic constipation, can result from enteric neuropathies, including both primary and secondary forms
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Inflammatory and degenerative cellular mechanisms can contribute to neural changes in primary and secondary neuropathies; understanding these mechanisms could promote the development of new therapeutic approaches for enteric neuropathies
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Acknowledgements
The authors of this Review are supported by grants PRIN and COFIN from the Italian Ministry of University, Research and Education 2008 and 2010 and Ricerca Fondamentale Orientata funds from the University of Bologna to R. De Giorgio. He is also the recipient of research grants from Fondazione Del Monte di Bologna e Ravenna. C. Knowles is funded by the Higher Education Funding Committee of England (HEFCE).
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Knowles, C., Lindberg, G., Panza, E. et al. New perspectives in the diagnosis and management of enteric neuropathies. Nat Rev Gastroenterol Hepatol 10, 206–218 (2013). https://doi.org/10.1038/nrgastro.2013.18
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DOI: https://doi.org/10.1038/nrgastro.2013.18
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