Post-inflammatory colonic afferent sensitisation: Different subtypes, different pathways and different time courses

P. A. Hughes, S. M. Brierley, C. M. Martin, S. J.H. Brookes, D. R. Linden, L. A. Blackshaw

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108 Scopus citations

Abstract

Objective: Intestinal infection evokes hypersensitivity in a subgroup of patients with irritable bowel syndrome (IBS) long after healing of the initial injury. Trinitrobenzene sulfonic acid (TNBS)-induced colitis in rodents likewise results in delayed maintained hypersensitivity, regarded as a model of some aspects of IBS. The colon and rectum have a complex sensory innervation, comprising five classes of mechanosensitive afferents in the splanchnic and pelvic nerves. Their plasticity may hold the key to underlying mechanisms in IBS. Our aim was therefore to determine the contribution of each afferent class in each pathway towards postinflammatory visceral hypersensitivity. Design: TNBS was administered rectally and mice were studied after 7 (acute) or 28 (recovery) days. In vitro preparations of mouse colorectum with attached pelvic or splanchnic nerves were used to examine the mechanosensitivity of individual colonic afferents. Results: Mild inflammation of the colon was evident acutely which was absent at the recovery stage. TNBS treatment did not alter proportions of the five afferent classes between treatment groups. In pelvic afferents little or no difference in response to mechanical stimuli was apparent in any class between control and acute mice. However, major increases in mechanosensitivity were recorded from serosal afferents in mice after recovery, while responses from other subtypes were unchanged. Both serosal and mesenteric splanchnic afferents were hypersensitive at both acute and recovery stages. Conclusions: Colonic afferents with high mechanosensory thresholds contribute to inflammatory hypersensitivity, but not those with low thresholds. Pelvic afferents become involved mainly following recovery from inflammation, whereas splanchnic afferents are implicated during both inflammation and recovery.

Original languageEnglish (US)
Pages (from-to)1333-1341
Number of pages9
JournalGut
Volume58
Issue number10
DOIs
StatePublished - Oct 1 2009

ASJC Scopus subject areas

  • Gastroenterology

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    Hughes, P. A., Brierley, S. M., Martin, C. M., Brookes, S. J. H., Linden, D. R., & Blackshaw, L. A. (2009). Post-inflammatory colonic afferent sensitisation: Different subtypes, different pathways and different time courses. Gut, 58(10), 1333-1341. https://doi.org/10.1136/gut.2008.170811