Experimental arthritis in the rat does not alter the analgesic potency of intrathecal or intraarticular morphine

To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (IA) or in trathecal (IT) morphine in tests of thermal and mechanical nociception chan ged during the induction of experimental arthritis in the rat. Thermal noci ception by IT morphine (3, 10, and 50 mu g) or IA morphine (100, 1000, and 3000 mu g) was assessed by means of a modified Hargreaves box ever) 28 h. M echanical antinociception was determined for the largest applied doses of m orphine using von Frey hairs. Morphine produced dose-dependent thermal anti nociception after IT or IA administration: a 50% increase in maximum antino ciceptive thermal response (50% effective dose) was produced by IT doses of 9.7 mu g at the start and 9.1 mu g at the end of this 28-h observational i nterval, whereas after IA administration, 50% effective dose values were 55 3 mu g at the start and 660 mu g at the end. The largest applied dose of ei ther IT or IA morphine produced mechanical antinociception. On Day 1, the a ntinociceptive effect for mechanical nociception (expressed as the area und er the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for IT morphine 50 mu g and 53% for IA morphine 3000 m u g. Neither result differed from the corresponding area under the curve va lues on Day 2. Naloxone administered either IT or LA abolished the antinoci ceptive action of morphine given at the same site. We conclude that, althou gh morphine has a peripheral analgesic site of action in a rat arthritis mo del, its potency for both IA and IT routes of administration does not chang e during the onset of arthritis. Implications: In this animal study, we sho wed that the administration of morphine modulates thermal and mechanical an tinociception at central and peripheral sites in inflammatory pain.