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Neurogastroenterol Motil. 2019 Jul 23:e13688. doi: 10.1111/nmo.13688. [Epub ahead of print]

µ-opioid receptor, β-endorphin, and cannabinoid receptor-2 are increased in the colonic mucosa of irritable bowel syndrome patients.

Author information

1
Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
2
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
3
G. Oppenheimer Family Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA, USA.
4
Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
5
Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Abstract

BACKGROUND AND AIMS:

The gut immune, cannabinoid, and opioid systems constitute an integrated network contributing to visceral sensation and pain modulation. We aimed to assess the expression of the µ-opioid receptor (MOR), its ligand β-endorphin (β-END), and cannabinoid receptor-2 (CB2 ) in patients with irritable bowel syndrome (IBS) and asymptomatic controls (AC) and their correlation with sex and symptom perception.

METHODS:

Mucosal biopsies were obtained from the left colon of 31 IBS patients (45% women) with predominant constipation (IBS-C, 9) or diarrhea (IBS-D, 10) or with mixed bowel habits (IBS-M, 12) and 32 AC (44% women) and processed for qRT-PCR, Western blotting, and immunohistochemistry.

KEY RESULTS:

µ-opioid receptor and CB2 mRNA and protein expression and β-END protein levels were increased in patients with IBS compared to AC (all Ps=0.021). A significant sex by IBS interaction was found in relation to CB2 mRNA expression (P = .003) with women showing a markedly higher expression to men (P = .035). In contrast, in AC, men had higher expression than women (P = .033). β-END, MOR, and CB2 immunoreactivities (IR) were localized to CD4+T cells including EMR-1+ eosinophils and CD31+ T cells but not to mast cells.

CONCLUSIONS:

The increased expression of MOR, β-END, and CB2 in the mucosa of IBS patients, where they are localized to immune cells, suggests that opioid and cannabinoid systems play an immune-related compensatory role in visceral pain in IBS patients. Further work is necessary to support this hypothesis.

KEYWORDS:

cannabinoid; immune system; irritable bowel syndrome; neuro-immune cross talk; opioid

PMID:
31336406
DOI:
10.1111/nmo.13688

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