Analgesia and serum concentrations of extradural, subdural and intraperitoneal fentanyl in a rat model

The effects of epidural, subdural and intraperitoneal fentanyl were determined on the tail flick response of the rat using the response latency as a measure of analgesia. Dose-time-response curves were generated for incremental doses of fentanyl administered at constant injection volumes. Serum concentrations at varying doses were determined using a radioimmunoassay technique. It was found that serum concentrations for extradural, subdural and intraperitoneal fentanyl were similar at the low doses, but differed significantly at higher doses suggesting that pharmacokinetic differences may be concentration dependent. Extradural administration of naloxone (0.004 mg) was able to antagonize extradural fentanyl (8.0 micrograms), a dose eight-fold greater than the lowest maximally effective dose. The relationship between serum fentanyl concentrations and administered doses suggest that the analgesic properties of extradural and subdural fentanyl are in part dependent on centrally mediated actions.