Role of gabapentin in preventing fentanyl- and morphine-withdrawal-induced hyperalgesia in rats.

PURPOSE

This study was undertaken to examine the effect of gabapentin for preventing hyperalgesia induced by morphine and fentanyl withdrawal in rats.

METHODS

To induce hyperalgesia, Sprague Dawley (SD) rats were subcutaneously injected with fentanyl four times at 15-min intervals (60 μg/kg per injection), resulting in total dose of 240 μg/kg over 1 h, and morphine 10 mg/kg twice daily for 7 days. The effect of gabapentin was detected with behavioral tail-flick and paw-withdrawal tests.

RESULTS

Drug termination produced significant decrease in antinociception thresholds (P < 0.05 vs. saline group), indicating that the rats became sensitive to thermal stimuli. In rats that received combined treatment with fentanyl/morphine and gabapentin (25/50 mg/kg), results demonstrated that there were no significant decreases in antinociception thresholds (vs. saline group) after opioid withdrawal. Gabapentin (50 mg/kg) could also prevent morphine tolerance. The 50% effective dose (ED50) value was 12.5 mg/kg in tail-flick and 13.6 mg/kg in paw-withdrawal tests.

CONCLUSIONS

The study showed that gabapentin can significantly prevented opioid-induced hyperalgesia (OIH) induced caused by fentanyl and morphine, suggesting a role for the addition of gabapentin in the perioperative period and during chronic pain treatment as an effective drug to prevent OIH.