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REGIONAL ANESTHESIA AND PAIN MANAGEMENT

Experimental Arthritis in the Rat Does Not Alter the Analgesic Potency of Intrathecal or Intraarticular Morphine

Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische Wilhelms-Universität Münster, Münster, Germany

Address correspondence to Hartmut Buerkle, MD, Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany. Address e-mail to buerkle{at}uni-muenster.de

To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (IA) or intrathecal (IT) morphine in tests of thermal and mechanical nociception changed during the induction of experimental arthritis in the rat. Thermal nociception by IT morphine (3, 10, and 50 µg) or IA morphine (100, 1000, and 3000 µg) was assessed by means of a modified Hargreaves box ever) 28 h. Mechanical antinociception was determined for the largest applied doses of morphine using von Frey hairs. Morphine produced dose-dependent thermal antinociception after IT or IA administration: a 50% increase in maximum antinociceptive thermal response (50% effective dose) was produced by IT doses of 9.7 µg at the start and 9.1 µg at the end of this 28-h observational interval, whereas after IA administration, 50% effective dose values were 553 µg at the start and 660 µg at the end. The largest applied dose of either IT or IA morphine produced mechanical antinociception. On Day 1, the antinociceptive effect for mechanical nociception (expressed as the area under the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for IT morphine 50 µg and 53% for IA morphine 3000 µg. Neither result differed from the corresponding area under the curve values on Day 2. Naloxone administered either IT or IA abolished the antinociceptive action of morphine given at the same site. We conclude that, although morphine has a peripheral analgesic site of action in a rat arthritis model, its potency for both IA and IT routes of administration does not change during the onset of arthritis.

Implications: In this animal study, we showed that the administration of morphine modulates thermal and mechanical antinociception at central and peripheral sites in inflammatory pain.

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