Opioid-induced bowel dysfunction in healthy volunteers assessed with questionnaires and MRI

TY - JOUR

T1 - Opioid-induced bowel dysfunction in healthy volunteers assessed with questionnaires and MRI

AU - Nilsson, Matias

AU - Poulsen, Jakob L.

AU - Brock, Christina

AU - Sandberg, Thomas H

AU - Gram, Mikkel

AU - Frøkjr, Jens B.

AU - Krogh, Klaus

AU - Drewes, Asbjørn M.

PY - 2016

Y1 - 2016

N2 - 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. Conclusion 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.

AB - 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. Conclusion 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.

KW - Adverse effects

KW - Constipation

KW - Healthy volunteers

KW - MRI

KW - Opioidinduced bowel dysfunction

U2 - 10.1097/MEG.0000000000000574

DO - 10.1097/MEG.0000000000000574

M3 - Journal article

C2 - 26795566

AN - SCOPUS:84954571613

SN - 0954-691X

VL - 28

SP - 514

EP - 524

JO - European Journal of Gastroenterology and Hepatology

JF - European Journal of Gastroenterology and Hepatology

IS - 5

ER -