Effect of fluvoxamine on sufentanil antinociception and tolerance under chronic intravenous infusion in rats

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), significantly potentiates analgesia when administered in animals together with opioids. The aim of the present study was to investigate the effects of fluvoxamine on sufentanil antinociception and tolerance. Following animal care committe e approval, the effects of continuous infusions of fluvoxamine and sufentan il were studied in behavioural tests (hot-plate test, tail-flick test, cata lepsy test) in Sprague-Dawley rats with a jugular vein catheter. Saline was administered as a control. The time-effect curves for continuous intraveno us sufentanil indicate dose-related antinociception and rapid development o f tolerance in the hot-plate and tail-flick tests. Go-administration of flu voxamine with continuous sufentanil enhances antinociception and attenuates development of tolerance, most clearly seen in the tail-flick test. Fluvox amine alone and saline were not effective. No animal showed catalepsy. As a side effect we observed a marked loss of body weight. The IC50 values of s ufentanil binding with and without fluvoxamine addition are 0.56+/-0.17 nM and 0.3+/-0.15 nM, respectively, indicating no direct effect on the occupan cy of sufentanil on the Ir-receptor by this serotonin reuptake inhibitor. I n conclusion, we were able to show that the combination of an opioid with a n SSRI at low doses improves analgesia and decreases development of toleran ce in nociceptive tests in rats. The clinical implications of these promisi ng results in an animal model, however, await further investigation.