Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain

Persistent Link:
http://hdl.handle.net/10150/610213
Title:
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, Devki; Okun, 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, USA; Arizona 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
Publisher:
BioMed Central
Citation:
Sukhtankar et al. Molecular Pain 2011, 7:81 http://www.molecularpain.com/content/7/1/81
Journal:
Molecular Pain
Rights:
© 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:
1744-8069
DOI:
10.1186/1744-8069-7-81
Version:
Final published version
Additional Links:
http://mpx.sagepub.com/content/7/1744-8069-7-81.full

Full metadata record

DC FieldValue Language
dc.contributor.authorSukhtankar, Devkien
dc.contributor.authorOkun, Alecen
dc.contributor.authorChandramouli, Anupamaen
dc.contributor.authorNelson, Marken
dc.contributor.authorVanderah, Todden
dc.contributor.authorCress, Anneen
dc.contributor.authorPorreca, Franken
dc.contributor.authorKing, Tamaraen
dc.date.accessioned2016-05-20T09:01:15Z-
dc.date.available2016-05-20T09:01:15Z-
dc.date.issued2011en
dc.identifier.citationSukhtankar et al. Molecular Pain 2011, 7:81 http://www.molecularpain.com/content/7/1/81en
dc.identifier.doi10.1186/1744-8069-7-81en
dc.identifier.urihttp://hdl.handle.net/10150/610213-
dc.description.abstractBACKGROUND: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.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://mpx.sagepub.com/content/7/1744-8069-7-81.fullen
dc.rights© 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)en
dc.titleInhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone painen
dc.typeArticleen
dc.identifier.eissn1744-8069en
dc.contributor.departmentDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USAen
dc.contributor.departmentArizona Cancer Center, University of Arizona, Tucson, AZ 85724, USAen
dc.contributor.departmentDepartment of Pathology, College of Medicine, University of Arizona, Tucson, AZ 85724, USAen
dc.contributor.departmentDepartment of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USAen
dc.identifier.journalMolecular Painen
dc.description.collectioninformationThis 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.en
dc.eprint.versionFinal published versionen
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