Korean J Pain.  2005 Jun;18(1):10-14. 10.3344/kjp.2005.18.1.10.

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

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea. dmyoon@yumc.yonsei.ac.kr
  • 2Department of Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.

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 ED50 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. ED50 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.

Keyword

antinociception; drug interaction; ketorolac; morphine; thermal stimulation

MeSH Terms

Analgesics, Opioid
Animals
Anti-Inflammatory Agents, Non-Steroidal
Drug Interactions
Ketorolac*
Morphine*
Naloxone
Rats*
Receptors, Opioid
Analgesics, Opioid
Anti-Inflammatory Agents, Non-Steroidal
Ketorolac
Morphine
Naloxone
Receptors, Opioid
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