title: The impact of the opioids fentanyl and morphine on nociception and bone destruction in a murine model of bone cancer pain.
abstract: Chronic pain resulting from metastasis into skeleton of certain neoplastic diseases remains poorly understood and relatively resistant to analgesic treatment. Opioids are the principal axis in drug therapy for this type of pain, especially at the end stage of cancer. Our aim was to examine whether, fentanyl as well as morphine, two potent analgesic opioids commonly used to treat cancer pain, would inhibit pain and bone lesion-related responses in a murine model of bone cancer pain. Repeated administration of equianalgesic doses of fentanyl (0.16 mg/kg s.c. once a day) and morphine (20 mg/kg s.c. once a day) initiated at day 1 (prophylactic treatment) or at day 7 (curative treatment) after tumor cell inoculation in the femoral cavity consistently decreased bone pain symptoms and tumor growth-induced bone destruction (micro-CT bone structure parameters). Both fentanyl and morphine treatments resulted in clear antinociceptive properties as well as reductions in cancer cell-induced bone lesions. The present results demonstrate that fentanyl, and to some lesser degree morphine, has potential benefits in the treatment and development of bone cancer pain. As such, chronic administration of high doses of certain opioids like fentanyl may have clinical utility in the management of bone cancer pain.
authors.affiliation: Department Pain and Neurology, Johnson & Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, B-2340 Beerse, Belgium.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Mouedden
authors.forename: Theo Frans
authors.initials: TF
authors.lastname: Meert
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology*; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D005283:Fentanyl / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009020:Morphine / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D010147:Pain Measurement / Q000187:drug effects*; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology*; D004856:Postural Balance / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D005283:Fentanyl