Evaluation of pain-related behavior, bone destruction and effectiveness of fentanyl, sufentanil, and morphine in a murine model of cancer pain

被引:32
作者
El Mouedden, M [1 ]
Meert, TF [1 ]
机构
[1] Johnson & Johnson Pharmaceut, Res & Dev, Div Janssen Pharmaceut, B-2340 Beerse, Belgium
关键词
bone cancer; cancer pain; fentanyl; morphine; sufentanil; opioid; marine model; osteolysis; CT-scan; trabecular bone structure;
D O I
10.1016/j.pbb.2005.07.016
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
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 mu CT-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) oil 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: >= 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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:109 / 119
页数:11
相关论文
共 39 条
[11]  
Honore P, 2000, Prog Brain Res, V129, P389
[12]   Bone cancer pain: From mechanism to model to therapy [J].
Honore, P ;
Mantyh, PW .
PAIN MEDICINE, 2000, 1 (04) :303-309
[13]  
KANIS JA, 1991, BONE, V12, P13
[14]   A cannabinoid agonist differentially attenuates deep tissue hyperalgesia in animal models of cancer and inflammatory muscle pain [J].
Kehl, LJ ;
Hamamoto, DT ;
Wacnik, PW ;
Croft, DL ;
Norsted, BD ;
Wilcox, GL ;
Simone, DA .
PAIN, 2003, 103 (1-2) :175-186
[15]   A novel orthotopic model of breast cancer metastasis to bone [J].
Lelekakis, M ;
Moseley, JM ;
Martin, TJ ;
Hards, D ;
Williams, E ;
Ho, P ;
Lowen, D ;
Javni, J ;
Miller, FR ;
Slavin, J ;
Anderson, RL .
CLINICAL & EXPERIMENTAL METASTASIS, 1999, 17 (02) :163-170
[16]  
Lipton A, 2000, CANCER, V88, P1082, DOI 10.1002/(SICI)1097-0142(20000301)88:5<1082::AID-CNCR20>3.0.CO
[17]  
2-Z
[18]  
Luger NM, 2001, CANCER RES, V61, P4038
[19]   Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs. inflammatory pain [J].
Luger, NM ;
Sabino, MAC ;
Schwei, MJ ;
Mach, DB ;
Pomonis, JD ;
Keyser, CP ;
Rathbun, M ;
Clohisy, DR ;
Honore, P ;
Yaksh, TL ;
Mantyh, PW .
PAIN, 2002, 99 (03) :397-406
[20]   Molecular mechanisms of cancer pain [J].
Mantyh, PW ;
Clohisy, DR ;
Koltzenburg, M ;
Hunt, SP .
NATURE REVIEWS CANCER, 2002, 2 (03) :201-209