title: Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon.
abstract: OBJECTIVE
  Opioid therapy is associated with altered secretion and motility of the gut. The relative contribution of decreased secretion to the development of opioid-induced constipation remains unknown.
  
  
  METHODS
  Twenty-five healthy males were treated with oxycodone for 5 d in a placebo-controlled, randomised cross-over design. Gastrointestinal adverse effects were assessed with validated questionnaires (bowel function index and gastrointestinal symptom rating scale). Rectosigmoid mucosal biopsies were taken at baseline and on day 5 during both treatments and mounted in Ussing chambers. Electrogenic ion transport parameters (short circuit current (SCC) and slope conductance) were measured after addition of secretagogues (prostaglandin E2 (PGE2) (6 μm), theophylline (400 μm)), and an inhibitor (ouabain (200 μm)). Additionally, morphine (50 μm) was added to investigate the direct opioid effect on colonic mucosa.
  
  
  RESULTS
  Questionnaires showed pronounced bowel symptoms, including constipation during oxycodone treatment (eight-fold increase in bowel function index score from day 1 to day 5 (p < 0.001) while no significant change occurred during placebo treatment (p = 0.47). Basal SCC and slope conductance did not differ between treatments (all p > 0.05) and application with PGE2, theophylline, and ouabain yielded comparable results on all examinations (all p > 0.05). Morphine application consistently did not evoke a change in ion transport.
  
  
  CONCLUSIONS
  Compared to placebo, epithelial electrogenic ion transport is not altered in mucosal biopsies from the rectosigmoid colon following 5-d oxycodone treatment. The secretory mechanisms in isolated mucosa appear to play a negligible role in the development of opioid-induced constipation.
authors.affiliation: a Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark ;
authors.forename: Matias
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: a Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark ;|b Department of Drug Design and Pharmacology , University of Copenhagen , Copenhagen , Denmark ;
authors.forename: Christina
authors.initials: C
authors.lastname: Brock
authors.affiliation: a Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark ;
authors.forename: Jakob Lykke
authors.initials: JL
authors.lastname: Poulsen
authors.affiliation: c Department of Biomedical Sciences, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark ;
authors.forename: Niels
authors.initials: N
authors.lastname: Bindslev
authors.affiliation: d Abdominal Center K , Bispebjerg Hospital, University of Copenhagen , Copenhagen , Denmark ;|e AstraZeneca R&D , Mölndal , Sweden ;
authors.forename: Mark Berner
authors.initials: MB
authors.lastname: Hansen
authors.affiliation: b Department of Drug Design and Pharmacology , University of Copenhagen , Copenhagen , Denmark ;
authors.forename: Lona
authors.initials: L
authors.lastname: Louring Christrup
authors.affiliation: a Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark ;|f Department of Clinical Medicine , Aalborg University , Aalborg , Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage; D001706:Biopsy; D012809:Colon, Sigmoid / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003248:Constipation / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D005769:Gastrointestinal Motility / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage*; D012007:Rectum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone
keywords: Colon; Ussing chamber; constipation; human; mucosal secretion; opioid analgesics