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Anesth Analg 2006;102:1768-1774
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000205751.88422.41

PAIN MEDICINE

Morphine, Oxycodone, Methadone and Its Enantiomers in Different Models of Nociception in the Rat

Kim Lemberg, DDS, Vesa K. Kontinen, MD, PhD, Kaarin Viljakka, MD, Irene Kylänlahti, BSc, Jari Yli-Kauhaluoma, PhD, and Eija Kalso, MD, PhD

Department of Pharmacology, Institute of Biomedicine, University of Helsinki; Faculty of Pharmacy, Division of Pharmaceutical Chemistry, University of Helsinki. Pain Clinic, Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland

Address correspondence and reprint requests to Eija Kalso, MD, PhD, Pain Clinic, Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, P.O. Box 140, FIN-00029 HUS. Address e-mail to eija.kalso{at}helsinki.fi.

We studied the effects of the commonly used µ-opioid receptor agonists morphine, oxycodone, methadone and the enantiomers of methadone in thermal and mechanical models of acute pain and in the spinal nerve ligation model of neuropathic pain in rats. Subcutaneous administration of morphine, oxycodone, and methadone produced a dose-dependent antinociceptive effect in the tail flick, hotplate, and paw pressure tests. l-methadone, racemic methadone, and oxycodone had a similar dose-dependent antinociceptive effect, whereas the dose-response curve of morphine was shallower. In the spinal nerve ligation model of neuropathic pain, subcutaneous administration of morphine, oxycodone, methadone and l-methadone had antiallodynic effects in tests of mechanical and cold allodynia. l-methadone showed the strongest antiallodynic effect of the tested drugs. d-methadone was inactive in all tests. Morphine 5.0 mg/kg, oxycodone 2.5 mg/kg, and l-methadone 1.25 mg/kg decreased spontaneous locomotion 30 min after drug administration. In conclusion, in acute nociception all µ-opioid receptor agonists produced antinociception, with morphine showing the weakest effect. In nerve injury pain, l-methadone showed the greatest antiallodynic potency in both mechanical and cold allodynia compared with the other opioids. Opioids seem to have different profiles in different pain models. l-methadone should be studied for neuropathic pain in humans.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.