{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:10:49Z","timestamp":1770412249273,"version":"3.49.0"},"reference-count":28,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA030316"],"award-info":[{"award-number":["R01DA030316"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2014,11]]},"DOI":"10.1016\/j.ejphar.2014.09.008","type":"journal-article","created":{"date-parts":[[2014,9,17]],"date-time":"2014-09-17T23:18:35Z","timestamp":1410995915000},"page":"48-52","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":41,"special_numbering":"C","title":["Targeting putative mu opioid\/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model"],"prefix":"10.1016","volume":"743","author":[{"given":"Branden A.","family":"Smeester","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary M.","family":"Lunzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyup","family":"Akg\u00fcn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvin J.","family":"Beitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip S.","family":"Portoghese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2014.09.008_bib1","doi-asserted-by":"crossref","first-page":"11595","DOI":"10.1073\/pnas.1305461110","article-title":"Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception","volume":"110","author":"Akg\u00fcn","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejphar.2014.09.008_bib2","first-page":"3","volume":"Vol. 8","author":"Bonferroni","year":"1936"},{"key":"10.1016\/j.ejphar.2014.09.008_bib3","doi-asserted-by":"crossref","first-page":"5947","DOI":"10.1073\/pnas.121179198","article-title":"Glutamate antagonists: deadly liaisons with cancer","volume":"98","author":"Cavalheiro","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejphar.2014.09.008_bib4","doi-asserted-by":"crossref","first-page":"15219","DOI":"10.1073\/pnas.1107304108","article-title":"Expression of the metabotropic glutamate receptor 5 (mGluR5) induces melanoma in transgenic mice","volume":"108","author":"Choi","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejphar.2014.09.008_bib5","doi-asserted-by":"crossref","first-page":"6646","DOI":"10.1158\/1078-0432.CCR-11-1109","article-title":"Integrating pain metrics into oncology clinical trials","volume":"17","author":"Cleeland","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejphar.2014.09.008_bib6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0014-2999(80)90515-4","article-title":"Intrathecal morphine in mice: a new technique","volume":"67","author":"Hylden","year":"1980","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.09.008_bib7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00213-002-1287-8","article-title":"Inhibitory effects of MPEP, an mGluR5 antagonist, and memantine, an N-methyl-d-aspartate receptor antagonist, on morphine antinociceptive tolerance in mice","volume":"165","author":"Kozela","year":"2003","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.ejphar.2014.09.008_bib8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10787-013-0183-7","article-title":"Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments","volume":"21","author":"Muralidharan","year":"2013","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.ejphar.2014.09.008_bib9","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/S0166-2236(00)02007-5","article-title":"Peripheral metabotropic glutamate receptors: fight the pain where it hurts","volume":"24","author":"Neugebauer","year":"2001","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.ejphar.2014.09.008_bib10","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","article-title":"Metabotropic glutamate receptors: physiology, pharmacology, and disease","volume":"50","author":"Niswender","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.ejphar.2014.09.008_bib11","first-page":"81","article-title":"Clinical significance of metabotropic glutamate receptor 5 expression in oral squamous cell carcinoma","volume":"17","author":"Park","year":"2007","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.ejphar.2014.09.008_bib12","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.1074\/jbc.M705661200","article-title":"Direct interaction enables cross-talk between ionotropic and group i metabotropic glutamate receptors","volume":"283","author":"Perroy","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2014.09.008_bib13","first-page":"199","article-title":"Translational concepts of mGluR5 in synaptic diseases of the brain","volume":"6","author":"Piers","year":"2012","journal-title":"Front. Neuropharmacol."},{"key":"10.1016\/j.ejphar.2014.09.008_bib14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3389\/fphar.2012.00199","article-title":"Translational concepts of mGluR5 in synaptic diseases of the brain","volume":"3","author":"Piers","year":"2012","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.09.008_bib15","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1158\/1078-0432.CCR-11-1217","article-title":"Molecular pathways: dysregulated glutamatergic signaling pathways in cancer","volume":"18","author":"Prickett","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejphar.2014.09.008_bib16","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/sj.npp.1300315","article-title":"Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats","volume":"29","author":"Raghavendra","year":"2003","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.ejphar.2014.09.008_bib17","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/ALN.0b013e31823de68d","article-title":"Intrathecal injection of metabotropic glutamate receptor subtype 3 and 5 agonist\/antagonist attenuates bone cancer pain by inhibition of spinal astrocyte activation in a mouse model","volume":"116","author":"Ren","year":"2012","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2014.09.008_bib18","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/npp.2011.155","article-title":"The mu-opioid receptor and the NMDA receptor associate in PAG neurons: implications in pain control","volume":"37","author":"Rodriguez-Munoz","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.ejphar.2014.09.008_bib19","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejphar.2013.01.066","article-title":"The plasticity of the association between mu-opioid receptor and glutamate ionotropic receptor N in opioid analgesic tolerance and neuropathic pain","volume":"716","author":"Sanchez-Blazquez","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.09.008_bib20","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.neuropharm.2008.12.010","article-title":"Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the [mu]-opioid receptor","volume":"56","author":"Schr\u00f6der","year":"2009","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.ejphar.2014.09.008_bib21","doi-asserted-by":"crossref","first-page":"671386","DOI":"10.1155\/2012\/671386","article-title":"Effects of different electroacupuncture scheduling regimens on murine bone tumor-induced hyperalgesia: sex differences and role of inflammation","volume":"2012","author":"Smeester","year":"2012","journal-title":"Evidence-based Complement. Altern. Med."},{"key":"10.1016\/j.ejphar.2014.09.008_bib22","doi-asserted-by":"crossref","first-page":"387169","DOI":"10.1155\/2013\/387169","article-title":"The effect of electroacupuncture on osteosarcoma tumor growth and metastasis: analysis of different treatment regimens","volume":"2013","author":"Smeester","year":"2013","journal-title":"Evidence-based Complement. Altern. Med."},{"key":"10.1016\/j.ejphar.2014.09.008_bib23","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.tins.2003.08.007","article-title":"Malignant gliomas: perverting glutamate and ion homeostasis for selective advantage","volume":"26","author":"Sontheimer","year":"2003","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.ejphar.2014.09.008_bib24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0304-3940(03)00259-3","article-title":"The mGluR5 selective antagonist 6-methyl-2-(phenylethynyl)-pyridine reduces the spinal neuron pain-related activity in mononeuropathic rats","volume":"342","author":"Sotgiu","year":"2003","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.ejphar.2014.09.008_bib25","first-page":"379","article-title":"Pain and its interference with daily activities in medical oncology outpatients","volume":"16","author":"Te","year":"2013","journal-title":"Pain Physician"},{"key":"10.1016\/j.ejphar.2014.09.008_bib26","doi-asserted-by":"crossref","first-page":"9355","DOI":"10.1523\/JNEUROSCI.21-23-09355.2001","article-title":"Functional interactions between tumor and peripheral nerve: morphology, algogen identification, and behavioral characterization of a new murine model of cancer pain","volume":"21","author":"Wacnik","year":"2001","journal-title":"J. Neurosci."},{"key":"10.1016\/j.ejphar.2014.09.008_bib27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0028-3908(00)00113-1","article-title":"Metabotropic glutamate receptor subtype 5 (mGlu5) and nociceptive function. I. Selective blockade of mGlu5 receptors in models of acute, persistent and chronic pain","volume":"40","author":"Walker","year":"2001","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.ejphar.2014.09.008_bib29","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0028-3908(00)00114-3","article-title":"mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia","volume":"40","author":"Walker","year":"2001","journal-title":"Neuropharmacology"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299914006529?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299914006529?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T03:58:26Z","timestamp":1565841506000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299914006529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11]]},"references-count":28,"alternative-id":["S0014299914006529"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2014.09.008","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2014,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting putative mu opioid\/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2014.09.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}