Evaluation of pain-related behavior, bone destruction and effectiveness of fentanyl, sufentanil, and morphine in a murine model of cancer pain.
The present study was conducted to evaluate the pain development and bone destruction during bone cancer growth in a murine model of bone cancer pain and to evaluate the analgesic efficacy of fentanyl, sufentanil, and morphine in this model. C3H/HeNCrl mice were inoculated into the intramedullary space of the femur with osteolytic NCTC 2472 fibrosarcoma cells, and followed during a 3-week period to assess pain behaviors (spontaneous lifting and limb-use during forced ambulation on rotarod) and bone destruction (parameters indicative of bone lesions determined by microCT-scans of the tumor-bearing bones) during bone cancer growth. The results showed that in this murine model of cancer-induced bone pain, behavioural manifestations of pain emerge in parallel with the progression of bone destruction. The subcutaneous administration of fentanyl (0.025-0.64 mg/kg), sufentanil (0.005-0.04 mg/kg), and morphine (2.5-40 mg/kg) on the test days 15 and 22 post-inoculation reduced pain-related behaviors in a dose dependent manner. A complete relief from pain-related behaviors was achieved with the following doses: > or =0.16 mg/kg fentanyl, 0.02 mg/kg sufentanil, and 20 mg/kg morphine. In conclusion, the results showed a clear link between tumor growth-induced bone destruction and behavioral pain manifestations, the latter was effectively controlled by the opioids fentanyl, sufentanil, and morphine.
El Mouedden
Mohammed
M
Johnson & Johnson Pharmaceutical Research & Development a Division of Janssen Pharmaceutica N. V., Turnhoutseweg 30, B2340 Beerse, Belgium. melmoued@PRDBE.jnj.com
Meert
Theo Frans
TF
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal; D001859:Bone Neoplasms / Q000150:complications / Q000556:secondary*; D004195:Disease Models, Animal; D005283:Fentanyl / Q000627:therapeutic use*; D051379:Mice; D009020:Morphine / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D017409:Sufentanil / Q000627:therapeutic use*
D000701:Analgesics, Opioid; D009020:Morphine; D017409:Sufentanil; D005283:Fentanyl