beta-endorphin and Irritable-Bowel-Syndrome

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. 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.. µ-opioid receptor and CB. The increased expression of MOR, β-END, and CB

Topics: beta-Endorphin; Female; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Male; Receptor, Cannabinoid, CB2; Receptors, Opioid, mu; Sex Characteristics

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.

Topics: Adult; Animals; beta-Endorphin; Colon; Female; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Leukocytes, Mononuclear; Macrophages; Male; Mast Cells; Mice; Middle Aged; Monocytes; Sensory Receptor Cells

The gut is a major site of contact between immune and sensory systems and evidence suggests that patients with irritable bowel syndrome (IBS) have immune dysfunction. Here we show how this dysfunction differs between major IBS subgroups and how immunocytes communicate with sensory nerves.. Peripheral blood mononuclear cell supernatants from 20 diarrhoea predominant IBS (D-IBS) patients, 15 constipation predominant IBS (C-IBS) patients and 36 healthy subjects were applied to mouse colonic sensory nerves and effects on mechanosensitivity assessed. Cytokine/chemokine concentration in the supernatants was assessed by proteomic analysis and correlated with abdominal symptoms, and expression of cytokine receptors evaluated in colonic dorsal root ganglia neurons. We then determined the effects of specific cytokines on colonic afferents.. D-IBS supernatants caused mechanical hypersensitivity of mouse colonic afferent endings, which was reduced by infliximab. C-IBS supernatants did not, but occasionally elevated basal discharge. Supernatants of healthy subjects inhibited afferent mechanosensitivity via an opioidergic mechanism. Several cytokines were elevated in IBS supernatants, and levels correlated with pain frequency and intensity in patients. Visceral afferents expressed receptors for four cytokines: IL-1β, IL-6, IL-10 and TNF-α. TNF-α most effectively caused mechanical hypersensitivity which was blocked by a transient receptor potential channel TRPA1 antagonist. IL-1β elevated basal firing, and this was lost after tetrodotoxin blockade of sodium channels.. Distinct patterns of immune dysfunction and interaction with sensory pathways occur in different patient groups and through different intracellular pathways. Our results indicate IBS patient subgroups would benefit from selective targeting of the immune system.

Topics: Adult; Animals; beta-Endorphin; Case-Control Studies; Cells, Cultured; Colon; Constipation; Culture Media, Conditioned; Cytokines; Diarrhea; Female; Ganglia, Spinal; Humans; Irritable Bowel Syndrome; Leukocytes, Mononuclear; Male; Mice; Middle Aged; Neuroimmunomodulation; Neurons, Afferent; Pain; Receptors, Cytokine

The object of this study was to discover mental functions, humoral regulation and large intestinal motor dysfunction in patients with the irritable bowels syndrome (IBS) in order to develop principles of their differential correction. A group of 106 patients (26 men and 80 women) with the irritable bowels syndrome was examined. The IBS diagnosis was made in accordance with the Rome criteria (1999). The control group included 21 somatically healthy volunteers (16 women and 5 men). Patients from both of the groups underwent clinical and psychological as well as plasma beta-endorphin concentration studies; colonic motor activity was also studied in patients with the IBS by the method of electric colonoscopy. Mental changes and certain particular features of the large intestine humoral regulation and motor activity determining the differential treatment for this category of patients were discovered.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Antibody Formation; beta-Endorphin; Female; Gastrointestinal Motility; Humans; Intestine, Large; Irritable Bowel Syndrome; Male; Middle Aged; Neurotic Disorders