Intrathecal cyclooxygenase inhibitor administration attenuates morphine antinociceptive tolerance in rats C. -S. Wong, M. -M. Hsu, R. Chou, Y. -Y. Chou,

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Intrathecal cyclooxygenase inhibitor administration attenuates morphine antinociceptive tolerance in rats C. -S. Wong, M. -M. Hsu, R. Chou, Y. -Y. Chou, C. -S. Tung British Journal of Anaesthesia Volume 85, Issue 5, Pages 747-751 (November 2000) DOI: 10.1093/bja/85.5.747 Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 1 The thermal antinociceptive effects of intrathecally administered NS-398 and indomethacin in rats, determined by the tail-flick test. Neither drug had any antinociceptive effect. All data points are mean and sem for at least six rats. British Journal of Anaesthesia 2000 85, 747-751DOI: (10.1093/bja/85.5.747) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 2 The effects of NS-398 and indomethacin on the development of morphine tolerance. Tolerance was induced by injection of morphine (50 μg, i.t.) twice daily for 5 days. Tail-flick latency was measured on each of these 5 days. The effects of NS-398 or indomethacin on the development of morphine tolerance were tested by administering NS-398 (20 μg, i.t.) or indomethacin (20 μg, i.t.) 10 min before each morphine injection during tolerance induction. The antinociceptive effects of NS-398 (20 μg, i.t.) and indomethacin (20 μg, i.t.) alone were also examined on each of the 5 days. The ♦ shows the mean tail-flick latency of 30 rats injected with saline before the study. All data points are mean and sem for at least six rats. *P<0.01 compared with the group injected with morphine alone. British Journal of Anaesthesia 2000 85, 747-751DOI: (10.1093/bja/85.5.747) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions

Fig 3 The effects of NS-398 and indomethacin on the dose–response relationship for morphine antinociception, measured by the tail-flick test, before and after morphine tolerance had developed. The dose–response relationship and the effects of NS-398 (20 μg, i.t.; top) and indomethacin (20 μg i.t.; bottom) on this relationship were first examined on day 1. Tolerance was then induced by injection of morphine (50 μg i.t.) twice daily for 5 days. On day 5, the dose–response curve was shifted to the right. Neither NS-398 nor indomethacin affected the curve after tolerance had developed. When NS-398 (20 μg i.t.) or indomethacin (20 μg i.t.) was coinjected with morphine during the induction of tolerance, the morphine dose–response curves were shifted to the left on day 5. All data points are the mean and sem for at least six rats. British Journal of Anaesthesia 2000 85, 747-751DOI: (10.1093/bja/85.5.747) Copyright © 2000 British Journal of Anaesthesia Terms and Conditions