복강내 투여된 Morphine,Nalbuphine,Ketorolac이 흰쥐 Formalin Test에 미치는 진통효과

Abstract

BACKGROUND The antinociceptive effect and the potency of systemically administered morphine (micro-agonist), nalbuphine (agonist-antagonist), and ketorolac (cyclooxygenase inhibitor) was examined in rats using the formalin test. METHODS Male Sprague-Dawley rats (250~300 g) received intraperitoneal injection of either saline or 3 doses of each test drug (0.3, 1.0, 3.0 mg/kg of morphine, 0.3, 1.0, 3.0 mg/kg of nalbuphine, and 10, 30, 100 mg/kg of ketorolac) 30 minutes prior to formalin injection. 50 microliter of 10% formalin was injected into the dorsal surface of the right hindpaw after 1 minute of 4% halothane induction. The construction of the dose-response curves and the determination of doses producing 50% maximum possible effect (ED50) were computed. RESULTS Intraperitoneal injection of morphine, nalbuphine and ketorolac resulted in the significant, dose-dependent supression of both phases, but nalbuphine has a ceiling effect at high dose for analgesia at the phase I of the formalin test. The rank order of relative potency in rats to the formalin test was nalbuphine (1.16)>morphine (1)>>ketorolac (0.1) in phase I, morphine (1)>nalbuphine (0.61)>>ketorolac (0.02) in phase IIa, and morphine (1)>nalbuphine (0.57)>>ketorolac (0.03) in phase IIb. CONCLUSION Comparing the systemic analgesic potency, nalbuphine and ketorolac will be needed in dosages 1.5 and 50 times that of morphine, respectively. These results suggest that ketorolac is not good enough as a single analgesic drug in preemptive analgesia for major surgery.