Pharmacological evaluation of opioid and non-opioid analgesics in a murine bone cancer model of pain

The intramedulary injection of osteosarcoma cells in the mouse femur has served as a laboratory model to study bone cancer pain. However, the efficacy of different classes of analgesics has not fully been analyzed in this model. Therefore, the acute antinociceptive properties of different classes of drugs were evaluated on post-inoculation day 15 when the degrees of spontaneous pain and mechanical hypersensitivity in the ipsilateral inoculated hind paw reached almost their maximal effects. At high doses, the opioids fentanyl, morphine, and tramadol had full efficacies for all pain parameters tested. Antagonism experiments with naloxone (10 mg/kg s.c.) or its peripheral analogue methylnaltrexone (10 mg/kg s.c.), suggest that the analgesic effects of fentanyl were predominantly mediated by centrally located μ-opiate receptors.Acetaminophen, the non-steroidal anti-inflammatory drug indomethacin, and the COX-2-inhibitor celecoxib did not significantly improve pain behavior. The tricyclic antidepressants amitriptyline and desipramine significantly reduced spontaneous pain behavior but this only at sedative doses; the serotonin reuptake inhibitor fluoxetine had limited efficacy. Also with the anticonvulsants lamotrigine, topiramate, and gabapentin limited or no efficacies were found. In conclusion, the present study provided integrated information about the tumor-induced bone pain in mice, and clarified acute efficacies of different categories of analgesics for the spontaneous lifting, limb-use impairment, and mechanical hypersensitivity. Moreover, the finding that bone cancer-pain behaviors are attenuated by various established compounds further supports the validity of the murine bone cancer model for the study of bone cancer pain and its use for the identification of novel treatments.