beta-endorphin and Colitis

Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways.. Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca. Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca. Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD.

Topics: Adult; Aged; Animals; beta-Endorphin; Biopsy; Chronic Disease; Colitis; Colon; Cytokines; Ganglia, Spinal; Humans; Mice; Mice, Inbred C57BL; Middle Aged; Naloxone; Nociceptors; Patch-Clamp Techniques; Signal Transduction; Stress, Psychological

Primary exposure of mice to the nematode Heligmosomoides polygyrus infection reduces inflammation in an experimental model of colitis. The aim of the present investigation was to evaluate whether the reduced inflammation provoked by H. polygyrus L4 larvae in BALB/c mice treated with dextran sulphate sodium is associated with changed expression of opioids in the small intestine and colon. Colitis was induced by 5% Dextran sulphate sodium (DSS) oral administration for 3 days before oral infection with 200 infective larvae (L3) H. polygyrus until the end of the experiment, 6 days post-infection. Clinical disease symptoms were monitored daily. The expressions of proopiomelanocortin POMC1, MOR1 (Oprm1) - opioid receptor and β-endorphin were determined by RT-PCR, Western blot and immunoassay, respectively, in the colon and small intestine of mice. RT-PCR analysis of colon tissues showed up-regulation of the expression of POMC and MOR1 opioid-dependent genes in mice with DSS-induced colitis. H. polygyrus L4 larvae inhibited DSS-induced colitis symptoms that were correlated with increased IL-1β, TNF-α, IL-6, myeloperoxidase (MPO) concentration, macrophages infiltration and MOR1, POMC and β-endorphin increased expression in the small intestine and inhibition of those in the colon.

Topics: Animals; beta-Endorphin; Blotting, Western; Colitis; Cytokines; Dextran Sulfate; Gene Expression Profiling; Intestines; Larva; Macrophages; Male; Mice; Mice, Inbred BALB C; Nematospiroides dubius; Neutrophils; Peroxidase; Pro-Opiomelanocortin; Real-Time Polymerase Chain Reaction; Receptors, Opioid; Severity of Illness Index

Even though inflammation is a traditional tool for the induction of hyperalgesia in many tissues, recent observations suggest that not all inflammatory processes produce this change. Tolerance to colorectal distension (CRD) is reduced in patients with acute ulcerative colitis but is increased in patients with chronic inflammatory bowel disease. This suggests that the nature of the inflammatory infiltrate influences visceral perception.. To test this hypothesis by assessing responses to CRD in mice with mild, acute or chronic colitis.. CRD responses were measured in mice with mild non-specific colitis, and dextran sodium sulphate (DSS)-induced acute and chronic colitis. Responses were compared with tissue infiltrate and damage, interleukin (IL)1beta and myeloperoxidase (MPO) activity and substance P, beta-endorphin and micro opioid receptor (MOR) expression.. Mild and acute colitis were associated with increased responsiveness to CRD. In contrast, CRD responses were not increased in mice with chronic colitis and this difference was not due to altered colonic wall compliance. MPO and IL1beta levels were greater in acute than in chronic colitis. Larger increases in tissue substance P were seen in acute than in chronic DSS, whereas CD4 T cells, beta-endorphin and MOR expression were evident only in chronic colitis. An inverse correlation was seen between substance P and MOR in these tissues.. Acute colitis increased responsiveness to CRD and is accompanied by an acute inflammatory infiltrate and increased tissue substance P. Chronic DSS is accompanied by an increase in beta-endorphin and MOR expression, and CD4 T cells, but no change in compliance or CRD responses. We conclude that acute inflammation generates hyperalgesia, whereas chronic inflammation involves infiltration by lymphocytes accompanied by MOR and beta-endorphin up regulation, and this provides an antinociceptive input that restores normal visceral perception.

Topics: Acute Disease; Animals; beta-Endorphin; CD4-Positive T-Lymphocytes; Chronic Disease; Colitis; Colon; Compliance; Interleukin-1beta; Male; Mice; Mice, Inbred BALB C; Neuropeptides; Pain; Pain Threshold; Physical Stimulation; Receptors, Opioid, mu; Substance P

Abnormal content and proportion of leucin-and methionine-enkephalins and beta-endorphin were found in blood plasma of chronic colitis sufferers. Nonspecific ulcerative colitis was associated with relevant peptides deficiency varying with the disease gravity, whereas in catarrhal colitis the peptides concentration was significantly elevated. Endogenous opioid peptides seem to play a role in pathogenesis of various colitis forms.

Topics: Adult; beta-Endorphin; Chronic Disease; Colitis; Colitis, Ulcerative; Enkephalin, Leucine; Enkephalin, Methionine; Humans; Middle Aged