{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:59:00Z","timestamp":1792119540683,"version":"4.4.0"},"reference-count":39,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Research"],"published-print":{"date-parts":[[2006,1]]},"DOI":"10.1016\/j.brainres.2005.11.054","type":"journal-article","created":{"date-parts":[[2006,1,11]],"date-time":"2006-01-11T09:36:36Z","timestamp":1136972196000},"page":"35-44","source":"Crossref","is-referenced-by-count":50,"title":["Morphine hyperalgesia in mice is unrelated to opioid activity, analgesia, or tolerance: Evidence for multiple diverse hyperalgesic systems"],"prefix":"10.1016","volume":"1070","author":[{"given":"Aaron","family":"Juni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.brainres.2005.11.054_bib2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/0024-3205(94)00552-4","article-title":"The excitatory effects of morphine-3-glucuronide are attenuated by LY274614, a competitive NMDA receptor antagonist, and by midazolam, an agonist at the benzodiazepine site on the GABAA receptor complex","volume":"54","author":"Bartlett","year":"1994","journal-title":"Life Sci."},{"key":"10.1016\/j.brainres.2005.11.054_bib3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1600-0773.1994.tb00327.x","article-title":"Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites","volume":"75","author":"Bartlett","year":"1994","journal-title":"Pharmacol. Toxicol."},{"key":"10.1016\/j.brainres.2005.11.054_bib1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0306-3623(94)90025-6","article-title":"Effects of naltrexone pellet implantation on morphine tolerance and physical dependence in the rat","volume":"25","author":"Bhargava","year":"1994","journal-title":"Gen. Pharmacol."},{"key":"10.1016\/j.brainres.2005.11.054_bib4","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/S0196-9781(96)00215-X","article-title":"Effects of morphine-3-glucuronide on the antinociceptive activity of peptide and nonpeptide opioid receptor agonists in mice","volume":"17","author":"Bian","year":"1996","journal-title":"Peptides"},{"key":"10.1016\/j.brainres.2005.11.054_bib5","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1016\/0024-3205(91)90150-A","article-title":"Mu receptor binding of some commonly used opioids and their metabolites","volume":"48","author":"Chen","year":"1991","journal-title":"Life Sci."},{"issue":"2\u20133","key":"10.1016\/j.brainres.2005.11.054_bib6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0304-3959(99)00223-7","article-title":"Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance\/dependence liability","volume":"84","author":"Crain","year":"2000","journal-title":"Pain"},{"key":"10.1016\/j.brainres.2005.11.054_bib7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0006-8993(00)03010-9","article-title":"Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia","volume":"888","author":"Crain","year":"2001","journal-title":"Brain Res."},{"key":"10.1016\/j.brainres.2005.11.054_bib8","first-page":"74","article-title":"A method for determining loss of pain sensation","volume":"72","author":"D'amour","year":"1941","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.brainres.2005.11.054_bib9","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0304-3959(91)90225-M","article-title":"Hyperalgesia and myoclonus with intrathecal infusion of high-dose morphine","volume":"47","author":"De Conno","year":"1991","journal-title":"Pain"},{"key":"10.1016\/j.brainres.2005.11.054_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/bdd.2510140102","article-title":"Pharmacokinetics and pharmacodynamics of morphine-3-glucuronide in rats and its influence on the antinociceptive effect of morphine","volume":"14","author":"Ekblom","year":"1993","journal-title":"Biopharm. Drug Dispos."},{"key":"10.1016\/j.brainres.2005.11.054_bib11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0893-133X(95)00083-P","article-title":"N-methyl-d-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development","volume":"13","author":"Elliott","year":"1995","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.brainres.2005.11.054_bib12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0304-3959(92)90065-J","article-title":"Morphine-3-glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat","volume":"48","author":"Gong","year":"1992","journal-title":"Pain"},{"key":"10.1016\/j.brainres.2005.11.054_bib13","first-page":"403","article-title":"The effects of pain on opioid tolerance: how do we resolve the controversy?","volume":"48","author":"Gutstein","year":"1996","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.brainres.2005.11.054_bib14","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0006-8993(83)90216-0","article-title":"Daily rhythms of analgesia in mice: effects of age and photoperiod","volume":"279","author":"Kavaliers","year":"1983","journal-title":"Brain Res."},{"key":"10.1016\/j.brainres.2005.11.054_bib15","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0091-3057(02)00908-5","article-title":"Genetic variation in morphine analgesic tolerance: a survey of 11 inbred mouse strains","volume":"73","author":"Kest","year":"2002","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.brainres.2005.11.054_bib16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0014-2999(01)01084-6","article-title":"Uncompetitive NMDA receptor antagonists potentiate morphine antinociception recorded from the tail but not from the hind paw in rats","volume":"423","author":"Kozela","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.brainres.2005.11.054_bib17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1248\/bpb1978.14.187","article-title":"Species difference of site-selective glucuronidation of morphine","volume":"14","author":"Kuo","year":"1991","journal-title":"J. Pharmacobio-dyn."},{"key":"10.1016\/j.brainres.2005.11.054_bib18","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0006-8993(79)90849-7","article-title":"Morphine derivatives with diminished opiate receptor potency show enhanced central excitatory activity","volume":"174","author":"Labella","year":"1979","journal-title":"Brain Res."},{"key":"10.1016\/j.brainres.2005.11.054_bib19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0169-328X(00)00260-6","article-title":"A murine model of opioid-induced hyperalgesia","volume":"86","author":"Li","year":"2001","journal-title":"Mol. Brain Res."},{"key":"10.1016\/j.brainres.2005.11.054_bib20","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0024-3205(94)90106-6","article-title":"Morphine-3-glucuronide: silent regulator of morphine actions","volume":"55","author":"Lipkowski","year":"1994","journal-title":"Life Sci."},{"key":"10.1016\/j.brainres.2005.11.054_bib21","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1523\/JNEUROSCI.14-04-02301.1994","article-title":"Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C","volume":"14","author":"Mao","year":"1994","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2005.11.054_bib22","doi-asserted-by":"crossref","first-page":"8312","DOI":"10.1523\/JNEUROSCI.22-18-08312.2002","article-title":"Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity","volume":"22","author":"Mao","year":"2002","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2005.11.054_bib23","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.2042-7158.1978.tb13244.x","article-title":"An improved long-acting delivery system for narcotic antagonists","volume":"30","author":"Misra","year":"1978","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.brainres.2005.11.054_bib24","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.pain.2004.01.035","article-title":"Modulation of morphine analgesia by site-specific N-methyl-d-aspartate receptor antagonists: dependence on sex, site of antagonism, morphine dose, and time","volume":"109","author":"Nemmani","year":"2004","journal-title":"Pain"},{"key":"10.1016\/j.brainres.2005.11.054_bib25","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/neu.20091","article-title":"Antinociceptive and nociceptive actions of opioids","volume":"61","author":"Ossipov","year":"2004","journal-title":"J. Neurobiol."},{"key":"10.1016\/j.brainres.2005.11.054_bib26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0304-3940(99)00109-3","article-title":"Genetic differences in the antinociceptive effect of morphine and its potentiation by dextromethorphan in rats","volume":"263","author":"Plesan","year":"1999","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.brainres.2005.11.054_bib27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0006-8993(01)02990-0","article-title":"Cholera toxin-B subunit blocks excitatory opioid receptor-mediated hyperalgesic effects in mice, thereby unmasking potent opioid analgesia and attenuating opioid tolerance\/dependence","volume":"919","author":"Shen","year":"2001","journal-title":"Brain Res."},{"key":"10.1016\/j.brainres.2005.11.054_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00001756-200301200-00001","article-title":"Opioid-induced hyperalgesia: abnormal or normal pain?","volume":"14","author":"Simonnet","year":"2003","journal-title":"NeuroReport"},{"key":"10.1016\/j.brainres.2005.11.054_bib29","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1111\/j.1399-6576.1998.tb05378.x","article-title":"Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration? Six case histories","volume":"42","author":"Sjogren","year":"1998","journal-title":"Acta Anaesthesiol. Scand."},{"key":"10.1016\/j.brainres.2005.11.054_bib30","first-page":"409","article-title":"Pharmacodynamics of subcutaneously administered diacetylmorphine, 6-acetylmorphine and morphine in mice","volume":"218","author":"Umans","year":"1981","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.brainres.2005.11.054_bib31","doi-asserted-by":"crossref","first-page":"7074","DOI":"10.1523\/JNEUROSCI.20-18-07074.2000","article-title":"Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance","volume":"20","author":"Vanderah","year":"2000","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2005.11.054_bib32","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1523\/JNEUROSCI.21-01-00279.2001","article-title":"Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance","volume":"21","author":"Vanderah","year":"2001","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2005.11.054_bib33","first-page":"603","article-title":"Morphine metabolism in mouse brain","volume":"75","author":"Wahlstrom","year":"1986","journal-title":"NIDA Res. Monogr."},{"key":"10.1016\/j.brainres.2005.11.054_bib34","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/0006-8993(81)90176-1","article-title":"Intrathecal high dose morphine produces hyperalgesia in the rat","volume":"209","author":"Woolf","year":"1981","journal-title":"Brain Res."},{"key":"10.1016\/j.brainres.2005.11.054_bib35","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1749-6632.1998.tb09666.x","article-title":"The role of GM1 ganglioside in regulating excitatory opioid effects","volume":"845","author":"Wu","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.brainres.2005.11.054_bib36","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1523\/JNEUROSCI.4054-04.2005","article-title":"Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance","volume":"25","author":"Xie","year":"2005","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2005.11.054_bib37","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.tips.2003.10.005","article-title":"Opioid hyperalgesia and tolerance versus 5-HT1A receptor-mediated inverse tolerance","volume":"24","author":"Xu","year":"2003","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.brainres.2005.11.054_bib38","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1097\/00000542-198605000-00008","article-title":"High dose of spinal morphine produce a nonopiate receptor-mediated hyperesthesia: clinical and theoretic implications","volume":"64","author":"Yaksh","year":"1986","journal-title":"Anesthesiology"},{"key":"10.1016\/j.brainres.2005.11.054_bib39","first-page":"126","article-title":"Pharmacokinetics and pharmacodynamics of subcutaneous naltrexone pellets in the rat","volume":"237","author":"Yoburn","year":"1986","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899305016677?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899305016677?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,4,14]],"date-time":"2019-04-14T04:32:10Z","timestamp":1555216330000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006899305016677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["S0006899305016677"],"URL":"https:\/\/doi.org\/10.1016\/j.brainres.2005.11.054","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.9276.466753","asserted-by":"object"}]},"ISSN":["0006-8993"],"issn-type":[{"value":"0006-8993","type":"print"}],"subject":[],"published":{"date-parts":[[2006,1]]}}}