Potent and long lasting antinociceptive effects after injection of low doses of a mu-opioid receptor agonist, fentanyl, into the brachial plexus sheath of the rat

Abstract

The effect of administering low doses (0.5-1.5 micrograms) of the mu-opioid receptor agonist fentanyl into the right brachial plexus sheath of the rat was examined using the vocalization threshold to paw pressure test. Both forepaws were tested in each rat. Fentanyl injected into the right brachial plexus sheath at 0.5-1.5 micrograms/kg produced a localized, dose-dependent, potent and long lasting antinociceptive effect, as gauged on the right forepaw. At the lower dose used (0.5 microgram/kg of fentanyl), the antinociceptive effect was restricted to the right forepaw and lasted for more than 2 h. Increasing doses of fentanyl (1 and 1.5 micrograms/kg) induced potent effects, lasting up to 5-6 h or even longer. In complete contrast, fentanyl administered i.v. at the dose of 1 microgram/kg had a very transient effect, only lasting up to 25 min. The results of injection of low doses of the opioid antagonist naloxone when administered either i.v. or locally into the paw, on the effect of fentanyl suggest the involvement of a peripheral site of action of the opioid. The present findings suggest that, as already observed in patients in clinical situations, low doses of opiates delivered using this administration route may provide prolonged regional analgesia, with the potential of avoiding centrally mediated side effects.