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Type: Journal article
Title: Differential effect of morphine on gastrointestinal transit, colonic contractions and nerve-evoked relaxations in Toll-Like Receptor deficient mice
Author: Beckett, E.
Staikopoulos, V.
Hutchinson, M.
Citation: Scientific Reports, 2018; 8(1):5923-1-5923-13
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 2045-2322
Statement of
Elizabeth A. H. Beckett, Vasiliki Staikopoulos, Mark R. Hutchinson
Abstract: Toll-like receptors (TLRs) are expressed in enteric neurons, glia, gastrointestinal (GI) smooth muscle and mucosa, yet their functional roles in the GI tract are not fully understood. TLRs have been linked to many of the undesirable central effects of chronic opioid administration including hyperalgesia and dependence via activation of central microglia. Opioid-induced bowel dysfunction (OIBD) remains a primary reason for the reduction or withdrawal of opioid analgesics. Morphine-induced inhibition of colonic motility was assessed in vivo by GI transit studies and in vitro using isolated colons from wildtype (WT) and TLR deficient mice. Morphine slowed movement of ingested content in WT but this retardation effect was attenuated in TLR4 -/- and TLR2/4 -/- . In isolated colons, morphine reduced amplitude and frequency colonic migrating motor contractions in both WT and TLR2/4 -/- . Electrical field stimulation elicited distal colon relaxation that was potentiated by morphine in WT but not in TLR2/4 -/- . Inhibitory junction potentials were of similar amplitude and kinetics in WT and TLR2/4 -/- distal colon and not altered by morphine. Enteric nerve density and proportion of nitrergic nerves were similar in WT and TLR2/4 -/- distal colon. These data suggest an involvement of TLRs in opioid pharmacodynamics and thus a potential interventional target for OIBD.
Keywords: Muscle, Smooth
Gastrointestinal Tract
Nitrergic Neurons
Mice, Knockout
Analgesics, Opioid
Gastrointestinal Transit
Gastrointestinal Motility
Muscle Contraction
Toll-Like Receptor 2
Toll-Like Receptor 4
Description: Published online: 12 April 2018
Rights: © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI: 10.1038/s41598-018-23717-4
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