Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain
Author
Sukhtankar, DevkiOkun, Alec
Chandramouli, Anupama
Nelson, Mark
Vanderah, Todd
Cress, Anne
Porreca, Frank
King, Tamara
Affiliation
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USAArizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
Department of Pathology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA
Issue Date
2011
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BioMed CentralCitation
Sukhtankar et al. Molecular Pain 2011, 7:81 http://www.molecularpain.com/content/7/1/81Journal
Molecular PainRights
© 2011 Sukhtankar et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0).Collection Information
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.Abstract
BACKGROUND:Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs.RESULTS:In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden.CONCLUSIONS:Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.EISSN
1744-8069Version
Final published versionAdditional Links
http://mpx.sagepub.com/content/7/1744-8069-7-81.fullae974a485f413a2113503eed53cd6c53
10.1186/1744-8069-7-81
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Except where otherwise noted, this item's license is described as © 2011 Sukhtankar et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0).