The intratibial inoculation of NCTC 2472 cells induces an
osteosarcoma in C3H/HeJ mice. These mice show thermal hyperalgesic responses which may be blocked by the local administration of
opiates over the tibial tumoral mass (Menéndez L, Lastra A, Hidalgo A,
Meana A, Garcia E, Baamonde A. Peripheral
opioids act as
analgesics in
bone cancer pain in mice. NeuroReport 2003b; 14:867-9). The aim of this report was to characterize the
analgesic responses obtained by activating peripheral
opioid receptors in
bone cancer pain. Here, we initially describe that this
osteosarcoma induces mechanical as well as
thermal hyperalgesia.
Loperamide, an
opioid agonist unable to cross the blood-brain barrier, inhibits both thermal and
mechanical hyperalgesia when s.c. injected, locally over the tibial tumoral mass (7.5-75 microg) or distantly, under the fur of the neck (4 mg/kg). These
analgesic effects seem peripherally mediated since they are reverted by the administration of
naloxone methiodide (10 mg/kg) and because the withdrawal latencies of the contralateral, non-affected, paws remain unaltered. Furthermore, only
cyprodime (1 mg/kg) but not
naltrindole (0.1 mg/kg) or
nor-binaltorphimine (10 mg/kg) blocked these effects, showing the involvement of gamma-
opioid receptors in the peripheral
analgesia induced by
loperamide on thermal and
mechanical hyperalgesia. The advantages of using peripheral acting
opiates -- devoid of central colateral effects -- for the treatment of
cancer related pain are suggested.