Browse > Article

The Analgesic Interaction between Ketorolac and Morphine in Radiant Thermal Stimulation Rat  

Roh, Jang Ho (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine)
Choe, Dong Hun (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine)
Lee, Youn Woo (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine)
Yoon, Duck Mi (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine)
Publication Information
The Korean Journal of Pain / v.18, no.1, 2005 , pp. 10-14 More about this Journal
Abstract
Background: Previous studies have suggested synergistic analgesic drug interactions between NSAIDs and opioids in neuropathic and inflammatory pain models. The aim of this study was to investigate the analgesic drug interaction between intraperitoneal (IP) ketorolac and morphine in radiant thermal stimulation rat. Methods: Initially, we assessed the withdrawal latency time of the hindpaw to radiant thermal stimulation every 15 min for 1 hour and every 30 min for next 1 hour after IP normal saline 5 ml (control group). The latency time was changed into percent maximal possible effect (%MPE). Next, IP dose response curves were established for the %MPE of morphine (0.3, 1, 3, 10 mg/kg) and ketorolac (3, 10, 30 mg/kg) to obtain the $ED_{50}$ for each agent. And we confirmed that the IP morphine effect was induced by opioid receptor through IP morphine followed by IP naloxone. At last, we injected three doses of IP ketorolac (3, 10, 30 mg/kg) mixed with one dose of morphine (2 mg/kg) for fixed dose analysis. Results: IP morphine delayed the paw withdrawal latency time dose dependently, but not ketorolac. $ED_{50}$ of IP morphine was 2.1 mg/kg. And the IP morphine effect was reversed to control level by IP naloxone. IP ketorolac + morphine combination showed no further additional effects on paw withdrawal latency time over morphine only group. Conclusions: IP ketorolac did not produce antinociceptive effect during radiant thermal stimulation. There was neither additional nor synergistic analgesic interaction between IP morphine and ketorolac in thermal stimulation rat.
Keywords
antinociception; drug interaction; ketorolac; morphine; therrnal stimulation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Picard P, Bazin JE, Conio N, Ruiz F, Schoeffler P: Kecorolac potentiates morphine in poscoperative patient-controlled analgesia. Pain 1997; 73: 401-6.   DOI   ScienceOn
2 Lopez-Munoz FJ, Diaz-Reval MI, Terron JA, Deciga-Carnpos M: Analysis of the analgesic interactions between kecorolac and tramadol during arthritic nociception in rat. Eur J Pharmacol 2004; 484: 157-65.   DOI
3 Carney DE, Nicolette LA, Ramer MH, Minerd A, Baesl T]: Kecorolac reduces postoperative narcotic requirements. J Pediatr Surg 2001; 36: 76-9.   DOI   ScienceOn
4 Luo ZD: Pain research. Totowa, Humana Press. 2004, pp 11-23.
5 Tejwani GA, Rattan AK: Antagonism of antinociception produced by intrathecal clonidine by ketorolac in the rat: the role of the opioid system. Anesth Analg 2000; 90: 115 2-6.   DOI
6 Tortorici V, Vanegas H: Putative tole of medullary off- and on- cells in the antinociception produced by dipyrone (rnetamizol) administered systemically or microinjected into PAG. Pain 1994; 57: 197-205.   DOI   ScienceOn
7 Malmberg AB, Yaksh TL: Phatmacology of the spinal action of ketorolac, morphine, ST-91, U50488H, and L-PIA on the formalin test and an isobolographic analysis of the NSAID interaction. Anesthesiology 1993; 79: 270-81.   DOI   ScienceOn
8 Tallarida RJ, Murray RB: Manual of pharmacologic calculation with computer programs. 2nd ed. New York, Springer-Verlag. 1987, pp 1-95.
9 Duarte ID, dos Santos IR, Lorenzetti BB, Ferreira SH: Analgesia by direct antagonism of nociceptor sensitization involves the argininenitric oxide-cGMP pathway. Eur J Pharmacol 1992; 217: 225-7.   DOI
10 Wideman GL, Keffer M, Morris E, Doyle RT Jr, Jiang JG, Beaver WT: Analgesic efficacy of a combination of hydrocodone with ibuprofen in posroperative pain. Clin Pharmacol Ther 1999; 65: 66-76 .   DOI   ScienceOn
11 Gillis JC, Brogden RN: Kecorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 1997; 53: 139-88.   DOI   ScienceOn
12 Lazaro-Ibanez GG, Torres-Lopez JE, Granados-Soco V: Participation of the nitric oxide-cyclic GMP-ATP-sensitive K+ channel pathway in the antinociceptive action of ketorolac. Eur J Pharmacol 2001; 426:39-44.   DOI
13 Conklin DR, Eisenach JC: Intrathecal kecorolac enhances antinociception from clonidine. Anesth Analg 2003; 96: 191-4.   DOI   ScienceOn
14 Maves TJ, Pechman PS, Meller ST, Gebhart GF: Kerorolac potentiates morphine antinociception during visceral nociception in the rat. Anesthesiology 1994; 80: 1094-101.   DOI   ScienceOn
15 Munro HM, Walton SR, Malviya S, Merkel S, Voepel-Lewis T, Loder RT, et al: Low-dose kecorolac improves analgesia and reduces morphine requirements following posterior spinal fusion in adolescents. Can J Anaesth 2002; 49: 461-6.   DOI   ScienceOn
16 Lorenzetti BB, Ferreira SH: Mode of analgesic action of dipyrone: direct antagonism of inflammacory hyperalgesia. Eur J Pharmacol 1985; 114: 375-81.   DOI   ScienceOn
17 Lashbrook JM, Ossipov MH, Hunter JC, Raffa RB, Tallarida RJ, Porreca F: Synergistic antiallodynic effects of spinal morphine with kecorolac and selective COXl- and COX2-inhibicors in nerve-injured rats. Pain 1999; 82: 65-72.   DOI   ScienceOn
18 Kolesnikov YA, Wilson RS, Pasternak GW: The synergistic analgesic interactions between hydrocodone and ibuprofen. Anesth Analg 2003;97: 1721-3.   DOI   ScienceOn
19 Fletcher D, Benoist JM, Gautron M, Guilbaud G: Isobolographic analysis of interactions between intravenous morphine, propacetamol, and diclofenac in carrageenan-injected rats. Anesthesiology 1997; 87:317-26.   DOI   ScienceOn