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.