Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes, Patrick A., Moretta, Melissa, Lim, Amanda, Grasby, Dallas J., Bird, Daniel, Brierley, Stuart M., Liebregts, Tobias, Adam, Birgit, Ashley Blackshaw, L., Holtmann, Gerald, Bampton, Peter, Hoffmann, Peter, Andrews, Jane M., Zola, Heddy and Krumbiegel, Doreen (2014) Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients. Brain, Behavior, and Immunity, 42 191-203. doi:10.1016/j.bbi.2014.07.001

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Author Hughes, Patrick A.
Moretta, Melissa
Lim, Amanda
Grasby, Dallas J.
Bird, Daniel
Brierley, Stuart M.
Liebregts, Tobias
Adam, Birgit
Ashley Blackshaw, L.
Holtmann, Gerald
Bampton, Peter
Hoffmann, Peter
Andrews, Jane M.
Zola, Heddy
Krumbiegel, Doreen
Title Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients
Journal name Brain, Behavior, and Immunity   Check publisher's open access policy
ISSN 0889-1591
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.bbi.2014.07.001
Open Access Status Not Open Access
Volume 42
Start page 191
End page 203
Total pages 13
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Abstract Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit colo-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The β-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-Endorphin was identified predominantly in monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in μ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte/macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.
Keyword Irritable Bowel Syndrome
Visceral pain
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
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