Bone cancer pain model in mice: evaluation of pain behavior, bone destruction and morphine sensitivity.
The primary aim of the study was to correlate pain development during bone cancer growth with objectively obtained tumor-induced changes in bone morphology. Additionally morphine sensitivity of this bone pain was evaluated. Mice were injected into the femur with osteolytic NCTC2472 cells, and behaviorally followed during a 3-week period. During the observation period increasing pain behavior was observed in tumor-bearing animals. Tumor mice exhibited spontaneous and movement-evoked lifting, the latter evoked through non-noxious palpation of the tumor. Limb use during forced ambulation on a rotarod decreased to substantial non-use of the affected limb by day 23. On day 23, micro-computer tomography scans of the tumor-bearing bones were evaluated for bone destruction. Different bone parameters indicative of osteolysis or fragmentation were significantly correlated with pain behavior. In a separate group of mice the effects of different morphine doses on pain behavior were evaluated on days 17 and 21 of tumor growth. Spontaneous lifting and movement-evoked lifting were sensitive to morphine treatment, although stress-induced analgesia due to repeated restraint might minimize movement-evoked lifting in mice. Limb use during forced ambulation was only slightly ameliorated by high morphine doses.
Vermeirsch
Hilde
H
CNS Pain & Alzheimer, J & J Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. hvermeir@prdbe.jnj.com
Nuydens
Rony M
RM
Salmon
Philip L
PL
Meert
Theo F
TF
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D000701:Analgesics, Opioid; D009020:Morphine