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dc.contributor.authorZhang, Hong
dc.contributor.authorLund, Dominique M.
dc.contributor.authorCiccone, Haley A.
dc.contributor.authorStaatz, William D.
dc.contributor.authorIbrahim, Mohab M.
dc.contributor.authorLargent-Milnes, Tally M.
dc.contributor.authorSeltzman, Herbert H.
dc.contributor.authorSpigelman, Igor
dc.contributor.authorVanderah, Todd W.
dc.date.accessioned2019-02-27T22:00:26Z
dc.date.available2019-02-27T22:00:26Z
dc.date.issued2018-09
dc.identifier.citationZhang, H., Lund, D. M., Ciccone, H. A., Staatz, W. D., Ibrahim, M. M., Largent-Milnes, T. M., ... Vanderah, T. W. (2018). Peripherally restricted cannabinoid 1 receptor agonist as a novel analgesic in cancer-induced bone pain. Pain, 159(9), 1814-1823. https://doi.org/10.1097/j.pain.0000000000001278en_US
dc.identifier.issn0304-3959
dc.identifier.pmid29781960
dc.identifier.doi10.1097/j.pain.0000000000001278
dc.identifier.urihttp://hdl.handle.net/10150/631758
dc.description.abstractMany malignant cancers, including breast cancer, have a propensity to invade bones, leading to excruciating bone pain. Opioids are the primary analgesics used to alleviate this cancer-induced bone pain (CIBP) but are associated with numerous severe side effects, including enhanced bone degradation, which significantly impairs patients' quality of life. By contrast, agonists activating only peripheral CB1 receptors (CB1Rs) have been shown to effectively alleviate multiple chronic pain conditions with limited side effects, yet no studies have evaluated their role(s) in CIBP. Here, we demonstrate for the first time that a peripherally selective CB1R agonist can effectively suppress CIBP. Our studies using a syngeneic murine model of CIBP show that both acute and sustained administration of a peripherally restricted CB1R agonist, 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl} morpholine (PrNMI), significantly alleviated spontaneous pain behaviors in the animals. This analgesic effect by PrNMI can be reversed by a systemic administration but not spinal injection of SR141716, a selective CB1R antagonist. In addition, the cancer-induced bone loss in the animals was not exacerbated by a repeated administration of PrNMI. Furthermore, catalepsy and hypothermia, the common side effects induced by cannabinoids, were measured at the supratherapeutic doses of PrNMI tested. PrNMI induced mild sedation, yet no anxiety or a decrease in limb movements was detected. Overall, our studies demonstrate that CIBP can be effectively managed by using a peripherally restricted CB1R agonist, PrNMI, without inducing dose-limiting central side effects. Thus, targeting peripheral CB1Rs could be an alternative therapeutic strategy for the treatment of CIBP.en_US
dc.description.sponsorshipNIH-NCI grant [R01CA142115]; UC Center for Accelerated Innovation [U54HL119893]en_US
dc.language.isoenen_US
dc.publisherLIPPINCOTT WILLIAMS & WILKINSen_US
dc.relation.urlhttp://Insights.ovid.com/crossref?an=00006396-900000000-98957en_US
dc.rights© 2018 International Association for the Study of Pain.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectCannabinoidsen_US
dc.subjectCannabinoid receptor 1en_US
dc.subjectPeripherally restricted agonisten_US
dc.subjectPrNMIen_US
dc.subjectAnalgesicen_US
dc.subjectCanceren_US
dc.subjectPainen_US
dc.subjectChronicen_US
dc.subjectBone lossen_US
dc.subjectSide effectsen_US
dc.titlePeripherally restricted cannabinoid 1 receptor agonist as a novel analgesic in cancer-induced bone painen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Anesthesiolen_US
dc.identifier.journalPAINen_US
dc.description.note12 month embargo; published online: 1 September 2018en_US
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_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitlePAIN
dc.source.beginpage1


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