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We aimed to assess the expression of the \u00b5\u2010opioid receptor (MOR), its ligand \u03b2\u2010endorphin (\u03b2\u2010END), and cannabinoid receptor\u20102 (CB<jats:sub>2<\/jats:sub>) in patients with irritable bowel syndrome (IBS) and asymptomatic controls (AC) and their correlation with sex and symptom perception.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mucosal biopsies were obtained from the left colon of 31 IBS patients (45% women) with predominant constipation (IBS\u2010C, 9) or diarrhea (IBS\u2010D, 10) or with mixed bowel habits (IBS\u2010M, 12) and 32 AC (44% women) and processed for qRT\u2010PCR, Western blotting, and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>\u00b5\u2010opioid receptor and CB<jats:sub>2<\/jats:sub> mRNA and protein expression and \u03b2\u2010END protein levels were increased in patients with IBS compared to AC (all <jats:italic>Ps<\/jats:italic>=0.021). A significant sex by IBS interaction was found in relation to CB<jats:sub>2<\/jats:sub> mRNA expression (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.003) with women showing a markedly higher expression to men (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.035). In contrast, in AC, men had higher expression than women <jats:italic>(P<\/jats:italic>\u00a0=\u00a0.033). \u03b2\u2010END, MOR, and CB<jats:sub>2<\/jats:sub> immunoreactivities (IR) were localized to CD4+T cells including EMR\u20101+ eosinophils and CD31+ T cells but not to mast cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The increased expression of MOR, \u03b2\u2010END, and CB<jats:sub>2<\/jats:sub> in the mucosa of IBS patients, where they are localized to immune cells, suggests that opioid and cannabinoid systems play an immune\u2010related compensatory role in visceral pain in IBS patients. Further work is necessary to support this hypothesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13688","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T23:35:02Z","timestamp":1563924902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["\u00b5\u2010opioid receptor, \u03b2\u2010endorphin, and cannabinoid receptor\u20102 are increased in the colonic mucosa of irritable bowel syndrome patients"],"prefix":"10.1111","volume":"31","author":[{"given":"Giovanni","family":"Dothel","sequence":"first","affiliation":[{"name":"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"},{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Chang","sequence":"additional","affiliation":[{"name":"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"},{"name":"G. Oppenheimer Family Center for Neurobiology of Stress and Resilience University of California Los Angeles Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, David Geffen School of Medicine University of California Los Angeles Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Raffaella","family":"Barbaro","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7777-2936","authenticated-orcid":false,"given":"Cesare","family":"Cremon","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0559-4875","authenticated-orcid":false,"given":"Vincenzo","family":"Stanghellini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"De Ponti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emeran A.","family":"Mayer","sequence":"additional","affiliation":[{"name":"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"},{"name":"G. 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