Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon

TY - JOUR

T1 - Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon

AU - Nilsson, Matias

AU - Brock, Christina

AU - Poulsen, Jakob Lykke

AU - Bindslev, Niels

AU - Hansen, Mark Berner

AU - Louring Christrup, Lona

AU - Drewes, A M

PY - 2016/5/3

Y1 - 2016/5/3

N2 - 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. Materials and 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 m), theophylline (400 m)), and an inhibitor (ouabain (200 m)). Additionally, morphine (50 m) 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. Conclusion 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.

AB - 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. Materials and 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 m), theophylline (400 m)), and an inhibitor (ouabain (200 m)). Additionally, morphine (50 m) 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. Conclusion 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.

KW - Adult

KW - Analgesics, Opioid

KW - Biopsy

KW - Colon, Sigmoid

KW - Constipation

KW - Cross-Over Studies

KW - Dose-Response Relationship, Drug

KW - Follow-Up Studies

KW - Gastrointestinal Motility

KW - Healthy Volunteers

KW - Humans

KW - Intestinal Mucosa

KW - Ion Transport

KW - Male

KW - Middle Aged

KW - Oxycodone

KW - Rectum

KW - Time Factors

KW - Young Adult

KW - Journal Article

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.3109/00365521.2015.1116108

DO - 10.3109/00365521.2015.1116108

M3 - Journal article

C2 - 26610166

SN - 0085-5928

VL - 51

SP - 538

EP - 547

JO - Scandinavian Journal of Gastroenterology. Supplement

JF - Scandinavian Journal of Gastroenterology. Supplement

IS - 5

ER -