Differential behavioral effects of peripheral and systemic morphine and naloxone in a rat model of repeated acute inflammation

Background: It has been reported that opioid antinociceptive effects are en hanced in animal models of inflammation, but it remains unclear whether thi s sensitization to morphine is related to predominant central or peripheral increased effects. Methods: The authors compared the behavioral effects of intraplantar and in travenous morphine and naloxone in a rat model of repeated acute carrageena n-induced inflammation in which enhanced responses to noxious stimuli resul t from sensitization in peripheral tissues or central sensitization. The an tinociceptive effects of intraplantar morphine (50, 75, 100, 150, and 200 m ug), intravenous morphine (0.3, 0.6, and 1 mg/kg), and the pronociceptive e ffects of intraplantar naloxone methiodide (150 mug) and intravenous naloxo ne (1 mg/kg) against noxious pressure (vocalization thresholds to paw press ure) in rats were assessed 3 h after one or two carrageenan plantar injecti ons performed 7 days apart. Results: After the first carrageenan injection, intraplantar and intravenou s morphine produced significant increase of vocalization thresholds to paw pressure in inflamed but not in noninflamed paws. After the second carragee nan injection, the antinociceptive effects of intraplantar morphine were si gnificantly reduced compared with those obtained after the rust carrageenan injection, whereas effects of intravenous morphine were significantly enha nced and present in both hind paws. Intravenous naloxone demonstrated simil ar pronociceptive patterns after the first and second carrageenan injection . Intraplantar naloxone methiodide produced pronociceptive effects in infla med hind paw that were significantly enhanced after the second carrageenan injection. Conclusions: When inflammation is enhanced by recurrent stimulations, the a ntinociceptive effects of systemic morphine are enhanced. This increase is more likely related to central than peripheral sites of action, beyond endo genous opioid system activation.