Effect of asimadoline, a κ opioid agonist, on pain induced by colonic distension in patients with irritable bowel syndrome

• Published in: Alimentary pharmacology & therapeutics Vol. 20; no. 2; pp. 237 - 246
• Main Authors: Delvaux, M., Beck, A., Jacob, J., Bouzamondo, H., Weber, F. T., Frexinos, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 15-07-2004; Blackwell
• Subjects: Acetamides - therapeutic use; Administration, Oral; Adolescent; Adult; Aged; Biological and medical sciences; Digestive system; Dilatation - methods; Double-Blind Method; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Irritable Bowel Syndrome - drug therapy; Irritable Bowel Syndrome - pathology; Medical sciences; Middle Aged; Narcotic Antagonists - therapeutic use; Pain - prevention & control; Pain Measurement; Pain Threshold; Pharmacology. Drug treatments; Pressure; Pyrrolidines - therapeutic use; Human; Agonist; Analgesic; Pain; Irritable bowel syndrome; Digestive diseases; Intestinal disease; Asimadoline
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2004.01922.x

Summary
Background : Visceral hypersensitivity plays a major role in irritable bowel syndrome pathophysiology. Opioid κ receptors on afferent nerves may modulate it and be the target for new irritable bowel syndrome treatments.
Aim : This study evaluated the effect of the κ opioid agonist asimadoline on perception of colonic distension and colonic compliance in irritable bowel syndrome patients.
Method : Twenty irritable bowel syndrome female patients (Rome II criteria; 40 ± 13 years) and hypersensitivity to colonic distension (Pain threshold ≤32 mmHg) were included in a randomized double‐blind cross‐over trial comparing the effect of a single oral dose of asimadoline 0.5 mg or placebo on sensory thresholds (defined as a constant and sustained sensation) elicited by left colon phasic distension (5 mmHg steps, 5 min) up to a sensation of abdominal pain. Colonic compliance was compared by the slope of the pressure–volume curves.
Results : On asimadoline, pain threshold (mean ± s.d.) (29.8 ± 7.2 mmHg) was higher than on placebo (26.3 ± 7.8 mmHg), difference not statistically significant (P = 0.1756, anova). Area under curve of pain intensity rated at each distension step was significantly lower on asimadoline (89.3 ± 33.9, anova) than on placebo (108.1 ± 29.7) (P = 0.0411). Thresholds of perception of nonpainful distensions were not altered on asimadoline, as compared with placebo. Colonic compliance was not different on placebo and asimadoline.
Conclusion : Asimadoline decreases overall perception of pain over a wide range of pressure distension of the colon in irritable bowel syndrome patients, without altering its compliance. These data suggest that further studies should explore the potential benefit of asimadoline in treatment of pain in irritable bowel syndrome patients.