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dc.contributor.authorForte, Brittany L.
dc.contributor.authorSlosky, Lauren M.
dc.contributor.authorZhang, Hong
dc.contributor.authorArnold, Moriah R.
dc.contributor.authorStaatz, William D.
dc.contributor.authorHay, Meredith
dc.contributor.authorLargent-Milnes, Tally M.
dc.contributor.authorVanderah, Todd W.
dc.date.accessioned2017-01-11T01:22:46Z
dc.date.available2017-01-11T01:22:46Z
dc.date.issued2016-12
dc.identifier.citationAngiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain 2016, 157 (12):2709 PAINen
dc.identifier.issn0304-3959
dc.identifier.pmid27541850
dc.identifier.doi10.1097/j.pain.0000000000000690
dc.identifier.urihttp://hdl.handle.net/10150/621905
dc.description.abstractMany cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Angiotensin-(1-7) (Ang-(1-7)) binds and activates the Mas receptor (MasR). Angiotensin-(1-7)/MasR activation modulates inflammatory signaling after acute tissue insult, yet no studies have investigated whether Ang-(1-7)/MasR play a role in CIBP. We hypothesized that Ang-(1-7) inhibits CIBP by targeting MasR in a murine model of breast CIBP. 66.1 breast cancer cells were implanted into the femur of BALB/cAnNHsd mice as a model of CIBP. Spontaneous and evoked pain behaviors were assessed before and after acute and chronic administration of Ang-(1-7). Tissues were collected from animals for ex vivo analyses of MasR expression, tumor burden, and bone integrity. Cancer inoculation increased spontaneous pain behaviors by day 7 that were significantly reduced after a single injection of Ang-(1-7) and after sustained administration. Preadministration of A-779 a selective MasR antagonist prevented this reduction, whereas pretreatment with the AT(2) antagonist had no effect; an AT(1) antagonist enhanced the antinociceptive activity of Ang-(1-7) in CIBP. Repeated Ang-(1-7) administration did not significantly change tumor burden or bone remodeling. Data here suggest that Ang-(1-7)/MasR activation significantly attenuates CIBP, while lacking many side effects seen with opioids. Thus, Ang-(1-7) may be an alternative therapeutic strategy for the nearly 90% of patients with advanced-stage cancer who experience excruciating pain.
dc.description.sponsorshipCollege of Medicine at the University of Arizona; NIH- NCI [R01 CA142115-01]en
dc.language.isoenen
dc.publisherLIPPINCOTT WILLIAMS & WILKINSen
dc.relation.urlhttp://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00006396-201612000-00011en
dc.rightsCopyright © 2016 International Association for the Study of Pain. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAngiotensin 1-7en
dc.subjectMasRen
dc.subjectBreasten
dc.subjectCanceren
dc.subjectPainen
dc.subjectChronicen
dc.titleAngiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone painen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen
dc.contributor.departmentUniv Arizona, Coll Med, Dept Physiol, Evelyn McKnight Brain Insten
dc.identifier.journalPAINen
dc.description.noteOpen access article.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-06-23T10:17:07Z
html.description.abstractMany cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Angiotensin-(1-7) (Ang-(1-7)) binds and activates the Mas receptor (MasR). Angiotensin-(1-7)/MasR activation modulates inflammatory signaling after acute tissue insult, yet no studies have investigated whether Ang-(1-7)/MasR play a role in CIBP. We hypothesized that Ang-(1-7) inhibits CIBP by targeting MasR in a murine model of breast CIBP. 66.1 breast cancer cells were implanted into the femur of BALB/cAnNHsd mice as a model of CIBP. Spontaneous and evoked pain behaviors were assessed before and after acute and chronic administration of Ang-(1-7). Tissues were collected from animals for ex vivo analyses of MasR expression, tumor burden, and bone integrity. Cancer inoculation increased spontaneous pain behaviors by day 7 that were significantly reduced after a single injection of Ang-(1-7) and after sustained administration. Preadministration of A-779 a selective MasR antagonist prevented this reduction, whereas pretreatment with the AT(2) antagonist had no effect; an AT(1) antagonist enhanced the antinociceptive activity of Ang-(1-7) in CIBP. Repeated Ang-(1-7) administration did not significantly change tumor burden or bone remodeling. Data here suggest that Ang-(1-7)/MasR activation significantly attenuates CIBP, while lacking many side effects seen with opioids. Thus, Ang-(1-7) may be an alternative therapeutic strategy for the nearly 90% of patients with advanced-stage cancer who experience excruciating pain.


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Copyright © 2016 International Association for the Study of Pain. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
Except where otherwise noted, this item's license is described as Copyright © 2016 International Association for the Study of Pain. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).