[Prolonged antinociceptive effect after epidural injection of polyethylene glycol-morphine composites in rats]

Epidurally administered morphine is useful in the management of postoperative or cancer pain, and a reliable method which can produce prolongation of analgesia with a single dose may be very useful. We synthesized a polyethylene glycol-morphine (PEG-morphine) composites and examined the duration of analgesia after a single epidural administration dose of this agent in the rat. The molecular weight of PEG was functionally evaluated. PEG-morphine was injected surgically along the epidural space. Morphine in doses of 2.5, 5.0 and 7.5 mg and PEG only were administered. A second group of animals received intramuscular injections of PEG-morphine (5.0mg). Animals were then tested for analgesia using the tail-flick test. The antinociceptive effect of 7.5mg was significantly longer than that of 2.5mg or 5.0mg. Neither PEG alone nor intramuscular administration of PEG-morphine induced antinociceptive effect. Sensory blockade was reversible and the animal appeared to have normal sensory perception. We conclude that the antinociceptive effect of morphine is dose-dependent and its duration can be prolonged when administered as a PEG-morphine composite in the epidural space.