Effect of asimadoline, a kappa opioid agonist, on pain induced by colonic distension in patients with irritable bowel syndrome.
BACKGROUND
Visceral hypersensitivity plays a major role in irritable bowel syndrome pathophysiology. Opioid kappa receptors on afferent nerves may modulate it and be the target for new irritable bowel syndrome treatments.


OBJECTIVE
This study evaluated the effect of the kappa opioid agonist asimadoline on perception of colonic distension and colonic compliance in irritable bowel syndrome patients.


METHODS
Twenty irritable bowel syndrome female patients (Rome II criteria; 40 +/- 13 years) and hypersensitivity to colonic distension (Pain threshold < or = 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.


CONCLUSIONS
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.
Delvaux
M
M
Gastroenterology Department, CHU Rangueil, Toulouse, France. 106521.3337@compuserve.com
Beck
A
A
Jacob
J
J
Bouzamondo
H
H
Weber
F T
FT
Frexinos
J
J
D000081:Acetamides / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D004106:Dilatation / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold; D011312:Pressure; D011759:Pyrrolidines / Q000627:therapeutic use*
D000081:Acetamides; D009292:Narcotic Antagonists; D011759:Pyrrolidines; C092095:asimadoline