Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain

Persistent Link:
http://hdl.handle.net/10150/610212
Title:
Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain
Author:
Ghilardi, Joseph; Freeman, Katie; Jimenez-Andrade, Juan; Mantyh, William; Bloom, Aaron; Kuskowski, Michael; Mantyh, Patrick
Affiliation:
Research Service, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA; Department of Pharmacology, University of Arizona, 1656 E. Mabel, Tucson, AZ 85724, USA; GRECC, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA; Arizona Cancer Center,; University of Arizona, 1656 E. Mabel, Tucson, AZ 85724, USA
Issue Date:
2010
Publisher:
BioMed Central
Citation:
Ghilardi et al. Molecular Pain 2010, 6:87 http://www.molecularpain.com/content/6/1/87
Journal:
Molecular Pain
Rights:
© 2010 Ghilardi 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:
Pain often accompanies cancer and most current therapies for treating cancer pain have significant unwanted side effects. Targeting nerve growth factor (NGF) or its cognate receptor tropomyosin receptor kinase A (TrkA) has become an attractive target for attenuating chronic pain.In the present report, we use a mouse model of bone cancer pain and examine whether oral administration of a selective small molecule Trk inhibitor (ARRY-470, which blocks TrkA, TrkB and TrkC kinase activity at low nm concentrations) has a significant effect on cancer-induced pain behaviors, tumor-induced remodeling of sensory nerve fibers, tumor growth and tumor-induced bone remodeling. Early/sustained (initiated day 6 post cancer cell injection), but not late/acute (initiated day 18 post cancer cell injection) administration of ARRY-470 markedly attenuated bone cancer pain and significantly blocked the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor bearing bone, but did not have a significant effect on tumor growth or bone remodeling.These data suggest that, like therapies that target the cancer itself, the earlier that the blockade of TrkA occurs, the more effective the control of cancer pain and the tumor-induced remodeling of sensory nerve fibers. Developing targeted therapies that relieve cancer pain without the side effects of current analgesics has the potential to significantly improve the quality of life and functional status of cancer patients.
EISSN:
1744-8069
DOI:
10.1186/1744-8069-6-87
Version:
Final published version
Additional Links:
http://mpx.sagepub.com/content/6/1744-8069-6-87.full

Full metadata record

DC FieldValue Language
dc.contributor.authorGhilardi, Josephen
dc.contributor.authorFreeman, Katieen
dc.contributor.authorJimenez-Andrade, Juanen
dc.contributor.authorMantyh, Williamen
dc.contributor.authorBloom, Aaronen
dc.contributor.authorKuskowski, Michaelen
dc.contributor.authorMantyh, Patricken
dc.date.accessioned2016-05-20T09:01:13Z-
dc.date.available2016-05-20T09:01:13Z-
dc.date.issued2010en
dc.identifier.citationGhilardi et al. Molecular Pain 2010, 6:87 http://www.molecularpain.com/content/6/1/87en
dc.identifier.doi10.1186/1744-8069-6-87en
dc.identifier.urihttp://hdl.handle.net/10150/610212-
dc.description.abstractPain often accompanies cancer and most current therapies for treating cancer pain have significant unwanted side effects. Targeting nerve growth factor (NGF) or its cognate receptor tropomyosin receptor kinase A (TrkA) has become an attractive target for attenuating chronic pain.In the present report, we use a mouse model of bone cancer pain and examine whether oral administration of a selective small molecule Trk inhibitor (ARRY-470, which blocks TrkA, TrkB and TrkC kinase activity at low nm concentrations) has a significant effect on cancer-induced pain behaviors, tumor-induced remodeling of sensory nerve fibers, tumor growth and tumor-induced bone remodeling. Early/sustained (initiated day 6 post cancer cell injection), but not late/acute (initiated day 18 post cancer cell injection) administration of ARRY-470 markedly attenuated bone cancer pain and significantly blocked the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor bearing bone, but did not have a significant effect on tumor growth or bone remodeling.These data suggest that, like therapies that target the cancer itself, the earlier that the blockade of TrkA occurs, the more effective the control of cancer pain and the tumor-induced remodeling of sensory nerve fibers. Developing targeted therapies that relieve cancer pain without the side effects of current analgesics has the potential to significantly improve the quality of life and functional status of cancer patients.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://mpx.sagepub.com/content/6/1744-8069-6-87.fullen
dc.rights© 2010 Ghilardi 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.titleAdministration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer painen
dc.typeArticleen
dc.identifier.eissn1744-8069en
dc.contributor.departmentResearch Service, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417, USAen
dc.contributor.departmentDepartment of Pharmacology, University of Arizona, 1656 E. Mabel, Tucson, AZ 85724, USAen
dc.contributor.departmentGRECC, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417, USAen
dc.contributor.departmentArizona Cancer Center,en
dc.contributor.departmentUniversity of Arizona, 1656 E. Mabel, 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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