Morphine, oxycodone, methadone and its enantiomers in different models of nocice

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Anesth Analg. 2006 Jun;102(6):1768-74.

Morphine, oxycodone, methadone and its enantiomers in different

models of nociception in the rat.

Lemberg K, Kontinen VK, Viljakka K, Kylanlahti I, Yli-Kauhaluoma J,

Kalso E.

Department of Pharmacology, Institute of Biomedicine, University of

Helsinki, Finland.

We studied the effects of the commonly used mu-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 mu-

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.