Effects of the local administration of selective mu-, delta-and kappa-opioid receptor agonists on osteosarcoma-induced hyperalgesia.

Abstract

The stimulation of peripheral opioid receptors yields analgesic responses in a model of bone cancer-induced pain in mice. In order to know the type(s) of peripheral opiate receptors involved, the paw thermal withdrawal latencies were measured in C3H/HeJ mice bearing a tibial osteosarcoma, after administering selective agonists of mu-,delta-and kappa-opiate receptors. The peritumoral administration of DAGO (0.6-6 microg) inhibited the osteosarcoma-induced hyperalgesia at doses ineffective in healthy animals, the highest one even increasing the withdrawal latencies over the control values. Naloxone-methiodide (2 mg/kg) and cyprodime (1 mg/kg), but not naltrindole (0.1 mg/kg) nor nor-binaltorphimine (10 mg/kg), antagonized DAGO-induced analgesic effects, these therefore probably being mediated through peripheral mu-opioid receptors. The peritumoral injection of DPDPE (100 microg) induced analgesia which was inhibited by naloxone-methiodide and naltrindole but not by nor-binaltorphimine. Cyprodime partially antagonized the analgesia induced by 100 microg of DPDPE, but did not modify the effect induced by 30 microg of this agonist-a dose that restores the hyperalgesic latencies up to the control values. The antihyperalgesic effect induced by the peritumoral administration of U-50,488H (1 microg) was antagonized by naloxone-methiodide and nor-binaltorphimine, but not by cyprodime nor naltrindole, thus suggesting the involvement of peripheral kappa-opioid receptors. In conclusion, the stimulation of peripheral mu-, delta- and kappa-opioid receptors is a pharmacological strategy useful for relieving this experimental type of bone cancer-induced pain, the greatest analgesic effect being achieved by stimulating peripheral mu-opioid receptors.

• Authors: Ana Baamonde, Ana Lastra, Lucía Juárez, Verónica García, Agustín Hidalgo, Luis Menéndez
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 372 Issue 3 Pg. 213-9 (Nov 2005) ISSN: 0028-1298 [Print] Germany
• PMID: 16283255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Morphinans
• Narcotic Antagonists
• Receptors, Opioid
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• cyprodime
• norbinaltorphimine
• Naltrexone
• naltrindole

Topics

• Analgesics, Opioid (antagonists & inhibitors, pharmacology)
• Animals
• Bone Neoplasms (complications)
• Drug Interactions
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)- (antagonists & inhibitors, pharmacology)
• Hyperalgesia (drug therapy, etiology)
• Mice
• Morphinans (pharmacology)
• Naltrexone (analogs & derivatives, pharmacology)
• Narcotic Antagonists (pharmacology)
• Osteosarcoma (complications)
• Receptors, Opioid (agonists)