BEHAVIORAL EVIDENCE FOR A PERIPHERAL COMPONENT IN THE ENHANCED ANTINOCICEPTIVE EFFECT OF A LOW-DOSE OF SYSTEMIC MORPHINE IN CARRAGEENAN-INDUCED HYPERALGESIC RATS

This study reinvestigated the possible contribution of a peripheral action of systemic morphine in the modulation of the response to noxious pressure on inflamed paws, using a supraspinally integrated test and various low doses of naloxone. Rats received an injection of carrageenin into the right hindpaw which resulted in an ipsilateral inflammatory response and decreased threshold to noxious pressure. Four hours post-carrageenin, the injection of 1 mg/kg i.v. morphine induced a significantly enhanced antinociceptive effect on the inflamed compared to the non-inflamed paws. Intrapantar injection of extremely low doses of naloxone (0.5 and 1 mu-g in a volume of 0.1 ml) singnificantly reduced this effect (naloxone being more effective when administered at the same time as morphine, compared to 15 min later), while equal doses of naloxone given systemically were inactive. These data confirm that synergism of peripheral and central actions may result in the augmented analgesic potency of morphine in rats subjected to inflammatory conditions. In addition, they provide further evidence for the complexity of opioid actions in inflammatory processes. In particular, the results are in line with the hypothesis that the paradoxical antinociceptive effect of extremely low doses of i.v. naloxone described in several studies is due to a central action.