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

2006; Lippincott Williams & Wilkins; Volume: 102; Issue: 6 Linguagem: Inglês

10.1213/01.ane.0000205751.88422.41

1526-7598

Kim K. Lemberg, Vesa K. Kontinen, Kaarin M. Viljakka, Irene Kyl nlahti, Jari Yli‐Kauhaluoma, Eija Kalso,

Pain Management and Opioid Use

In Brief 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. IMPLICATIONS: Oxycodone, methadone, and especially l-methadone were more effective than morphine in all studied pain models in the rat, including a model of nerve injury pain. Morphine may not be the most effective opioid, whereas l-methadone could be an interesting option when treating neuropathic pain.