Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon
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Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon. / Nilsson, Matias; Brock, Christina; Poulsen, Jakob Lykke; Bindslev, Niels; Hansen, Mark Berner; Louring Christrup, Lona; Drewes, A M.
In: Scandinavian Journal of Gastroenterology, Vol. 51, No. 5, 2016, p. 538-47.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2016
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 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.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 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.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
VL - 51
SP - 538
EP - 547
JO - Scandinavian Journal of Gastroenterology. Supplement
JF - Scandinavian Journal of Gastroenterology. Supplement
SN - 0085-5928
IS - 5
ER -
ID: 173475949