title: Potentiation of acute morphine-induced analgesia measured by a thermal test in bone cancer-bearing mice.
abstract: Agonists of μ-opioid receptors are currently used in the management of cancer pain. However, several data suggest that the analgesic effect of morphine can diminish during the development of experimental tumors. By using a thermal test, we have studied whether the analgesic effect evoked by morphine is altered in mice bearing two painful bone tumors. The analgesic effect evoked by systemic morphine remained unaltered after the intratibial inoculation of B16-F10 melanoma cells and was potentiated after the inoculation of NCTC 2472 osteosarcoma cells. Although the number of spinal μ-opioid receptors measured by western blot studies was not augmented in osteosarcoma-bearing mice, the analgesia evoked by intrathecal (i.t.) morphine was also enhanced. The analgesic response produced by the spinal administration of the Gi/o protein activator mastoparan was amplified, whereas the analgesic response evoked by the i.t. administration of the N-type calcium channel blocker ω-conotoxin remained unaltered. The efficacy of the GIRK channel blocker tertiapin-Q to antagonize the analgesic effect produced by a maximal dose of morphine was also increased in osteosarcoma-bearing mice. Our results seem to indicate that the analgesic effect of morphine on thermal nociception can be enhanced in response to the development of particular bone tumors in mice, being this potentiation probably related to a greater efficacy of the transduction system driven by Gi/o proteins and GIRK channels.
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: González-Rodríguez
authors.forename: Sara
authors.initials: S
authors.lastname: Llames
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Ana
authors.initials: A
authors.lastname: Baamonde
authors.forename: Luis
authors.initials: L
authors.lastname: Menéndez
mesh_terms: D000698:Analgesia / Q000379:methods*; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage*; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement / Q000379:methods*; D017450:Receptors, Opioid, mu / Q000096:biosynthesis
chemical_list: D017450:Receptors, Opioid, mu; D009020:Morphine