Effects of the local administration of selective mu-, delta-and kappa-opioid receptor agonists on osteosarcoma-induced hyperalgesia.
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.
Baamonde
Ana
A
Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, C/ Julián Clavería 6, 33006, Oviedo, Asturias, Spain.
Lastra
Ana
A
Juárez
Lucía
L
García
Verónica
V
Hidalgo
Agustín
A
Menéndez
Luis
L
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D009019:Morphinans / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D012516:Osteosarcoma / Q000150:complications; D011957:Receptors, Opioid / Q000819:agonists*
D000701:Analgesics, Opioid; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C058450:cyprodime; C051844:norbinaltorphimine; D009271:Naltrexone; C055382:naltrindole