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µ‐opioid receptor, β‐endorphin, and cannabinoid receptor‐2 are increased in the colonic mucosa of irritable bowel syndrome patients
Author(s) -
Dothel Giovanni,
Chang Lin,
Shih Wendy,
Barbaro Maria Raffaella,
Cremon Cesare,
Stanghellini Vincenzo,
De Ponti Fabrizio,
Mayer Emeran A.,
Barbara Giovanni,
Sternini Catia
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13688
Subject(s) - medicine , irritable bowel syndrome , cannabinoid , cannabinoid receptor , opioid , opioid receptor , cannabinoid receptor type 2 , constipation , visceral pain , receptor , cannabinoid receptor agonists , gastroenterology , endocrinology , nociception , agonist
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 (CB 2 ) 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 CB 2 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 CB 2 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 CB 2 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 CB 2 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.