title: Opioid-induced bowel dysfunction in healthy volunteers assessed with questionnaires and MRI.
abstract: OBJECTIVE
  Opioid treatment is associated with numerous gastrointestinal adverse effects collectively known as opioid-induced bowel dysfunction (OIBD). Most current knowledge of the pathophysiology derives from animal studies limited by species differences and clinical studies, which have substantial confounders that make evaluation difficult. An experimental model of OIBD in healthy volunteers in a controlled setting is therefore highly warranted. The aim of this study was to assess bowel function in healthy volunteers during opioid treatment using subjective and objective methods.
  
  
  METHODS
  Twenty-five healthy men were assigned randomly to oxycodone or placebo for 5 days in a cross-over design. The analgesic effect was assessed with muscle pressure algometry and adverse effects were measured using questionnaires including the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptoms and the Bristol stool form scale. Colorectal volumes were determined using a newly developed MRI method.
  
  
  RESULTS
  Compared with baseline, oxycodone increased pain detection thresholds by 8% (P=0.02). Subjective OIBD was observed as increased bowel function index (464% increase; P<0.001), gastrointestinal symptom rating scale (37% increase; P<0.001) and patient assessment of constipation symptoms (198% increase; P<0.001). Objectively, stools were harder and drier during oxycodone treatment (P<0.001) and segmental colorectal volumes increased in the caecum/ascending colon by 41% (P=0.005) and in the transverse colon by 20% (P=0.005). No associations were detected between questionnaire scores and colorectal volumes.
  
  
  CONCLUSIONS
  Experimental OIBD in healthy volunteers was induced during oxycodone treatment. This model has potential for future interventional studies to discriminate the efficacies of different laxatives, peripheral morphine antagonists and opioid treatments.
authors.affiliation: Departments of aGastroenterology and Hepatology bRadiology, Mech-Sense, Aalborg University Hospital cDepartment of Clinical Medicine, Aalborg University, Aalborg dDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen eNeurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Matias
authors.initials: M
authors.lastname: Nilsson
authors.forename: Jakob L
authors.initials: JL
authors.lastname: Poulsen
authors.forename: Christina
authors.initials: C
authors.lastname: Brock
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Sandberg
authors.forename: Mikkel
authors.initials: M
authors.lastname: Gram
authors.forename: Jens B
authors.initials: JB
authors.lastname: Frøkjær
authors.forename: Klaus
authors.initials: K
authors.lastname: Krogh
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D003248:Constipation / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology; D018592:Cross-Over Studies; D003672:Defecation / Q000187:drug effects*; D003718:Denmark; D004311:Double-Blind Method; D005769:Gastrointestinal Motility / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000009:adverse effects*; D010147:Pain Measurement; D058748:Pain Perception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011237:Predictive Value of Tests; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone