{"id":"https://openalex.org/W1988029680","doi":"https://doi.org/10.1172/jci70236","title":"Opioid receptor\u2013triggered spinal mTORC1 activation contributes to morphine tolerance and hyperalgesia","display_name":"Opioid receptor\u2013triggered spinal mTORC1 activation contributes to morphine tolerance and hyperalgesia","publication_year":2014,"publication_date":"2014-01-01","ids":{"openalex":"https://openalex.org/W1988029680","doi":"https://doi.org/10.1172/jci70236","mag":"1988029680","pmid":"https://pubmed.ncbi.nlm.nih.gov/24382350","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/3904613"},"language":"en","primary_location":{"id":"doi:10.1172/jci70236","doi":"https://doi.org/10.1172/jci70236","is_oa":false,"landing_page_url":"https://doi.org/10.1172/jci70236","pdf_url":null,"source":{"id":"https://openalex.org/S114430552","display_name":"Journal of Clinical Investigation","issn_l":"0021-9738","issn":["0021-9738","1558-8238"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320279","host_organization_name":"American Society for Clinical Investigation","host_organization_lineage":["https://openalex.org/P4310320279"],"host_organization_lineage_names":["American Society for Clinical Investigation"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Investigation","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3904613","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5109966815","display_name":"Ji-Tian Xu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I38877650","display_name":"Zhengzhou University","ror":"https://ror.org/04ypx8c21","country_code":"CN","type":"education","lineage":["https://openalex.org/I38877650"]}],"countries":["CN","US"],"is_corresponding":false,"raw_author_name":"Ji-Tian Xu","raw_affiliation_strings":["Johns Hopkins University","Zhengzhou University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University","institution_ids":["https://openalex.org/I145311948"]},{"raw_affiliation_string":"Zhengzhou University","institution_ids":["https://openalex.org/I38877650"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100676347","display_name":"Jian\u2010Yuan Zhao","orcid":"https://orcid.org/0000-0001-9861-0330","observed_orcids":["https://orcid.org/0000-0001-9861-0330"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jian-Yuan Zhao","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102086080","display_name":"Xiuli Zhao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xiuli Zhao","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063153847","display_name":"Davinna L. Ligons","orcid":"https://orcid.org/0000-0002-5065-9589","observed_orcids":["https://orcid.org/0000-0002-5065-9589"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Davinna Ligons","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074901729","display_name":"Vinod Tiwari","orcid":"https://orcid.org/0000-0002-8491-2255","observed_orcids":["https://orcid.org/0000-0002-8491-2255"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Vinod Tiwari","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012015053","display_name":"Fidelis E. Atianjoh","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Fidelis E. Atianjoh","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083825774","display_name":"Chun\u2010Yi Lee","orcid":"https://orcid.org/0000-0002-4210-206X","observed_orcids":["https://orcid.org/0000-0002-4210-206X"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Chun-Yi Lee","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014170054","display_name":"Lingli Liang","orcid":"https://orcid.org/0000-0001-7594-387X","observed_orcids":["https://orcid.org/0000-0001-7594-387X"]},"institutions":[{"id":"https://openalex.org/I102322142","display_name":"Rutgers, The State University of New Jersey","ror":"https://ror.org/05vt9qd57","country_code":"US","type":"education","lineage":["https://openalex.org/I102322142"]},{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lingli Liang","raw_affiliation_strings":["Johns Hopkins University","Rutgers - The State University of New Jersey, Newark"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University","institution_ids":["https://openalex.org/I145311948"]},{"raw_affiliation_string":"Rutgers - The State University of New Jersey, Newark","institution_ids":["https://openalex.org/I102322142"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008612686","display_name":"Weidong Zang","orcid":"https://orcid.org/0000-0001-8365-4672","observed_orcids":["https://orcid.org/0000-0001-8365-4672"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I38877650","display_name":"Zhengzhou University","ror":"https://ror.org/04ypx8c21","country_code":"CN","type":"education","lineage":["https://openalex.org/I38877650"]}],"countries":["CN","US"],"is_corresponding":false,"raw_author_name":"Weidong Zang","raw_affiliation_strings":["Johns Hopkins University","Zhengzhou University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University","institution_ids":["https://openalex.org/I145311948"]},{"raw_affiliation_string":"Zhengzhou University","institution_ids":["https://openalex.org/I38877650"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070318474","display_name":"Dolores B. Njoku","orcid":"https://orcid.org/0000-0002-5458-4596","observed_orcids":["https://orcid.org/0000-0002-5458-4596"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dolores Njoku","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5089858947","display_name":"Srinivasa Naga Raja","orcid":"https://orcid.org/0000-0001-7991-7636","observed_orcids":["https://orcid.org/0000-0001-7991-7636"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Srinivasa N. Raja","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086332857","display_name":"Myron Yaster","orcid":"https://orcid.org/0000-0003-1087-4548","observed_orcids":["https://orcid.org/0000-0003-1087-4548"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Myron Yaster","raw_affiliation_strings":["Johns Hopkins University ("],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Johns Hopkins University (","institution_ids":["https://openalex.org/I145311948"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5031447561","display_name":"Yuan\u2010Xiang Tao","orcid":"https://orcid.org/0000-0003-1777-3272","observed_orcids":["https://orcid.org/0000-0003-1777-3272"]},"institutions":[{"id":"https://openalex.org/I4402554120","display_name":"Rutgers New Jersey Medical School","ror":"https://ror.org/014ye1258","country_code":"US","type":"education","lineage":["https://openalex.org/I102322142","https://openalex.org/I4390039302","https://openalex.org/I4402554120"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Yuan-Xiang Tao","raw_affiliation_strings":["New Jersey Medical School (NJMS), Anesthesiology"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"New Jersey Medical School (NJMS), Anesthesiology","institution_ids":["https://openalex.org/I4402554120"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5031447561"],"corresponding_institution_ids":["https://openalex.org/I4402554120"],"apc_list":{"value":5200,"currency":"USD","value_usd":5200},"apc_paid":null,"fwci":12.409,"has_fulltext":false,"cited_by_count":169,"citation_normalized_percentile":{"value":0.99153673,"is_in_top_1_percent":true,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":94,"max":100},"biblio":{"volume":"124","issue":"2","first_page":"592","last_page":"603"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.9961000084877014,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.9961000084877014,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11199","display_name":"Pain Management and Opioid Use","score":0.0010999999940395355,"subfield":{"id":"https://openalex.org/subfields/2703","display_name":"Anesthesiology and Pain Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10814","display_name":"Neuropeptides and Animal Physiology","score":0.0006000000284984708,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/opioid-tolerance","display_name":"opioid tolerance","score":0.8220000267028809},{"id":"https://openalex.org/keywords/mu-opioid-receptor","display_name":"mu-opioid receptor","score":0.7799999713897705},{"id":"https://openalex.org/keywords/mtorc1","display_name":"mTORC1","score":0.8600000143051147},{"id":"https://openalex.org/keywords/pi3k-akt-signaling","display_name":"PI3K/Akt signaling","score":0.8889999985694885},{"id":"https://openalex.org/keywords/mrna-translation","display_name":"mRNA translation","score":0.7419999837875366},{"id":"https://openalex.org/keywords/spinal-dorsal-horn-neurons","display_name":"dorsal horn neurons","score":0.8539999723434448},{"id":"https://openalex.org/keywords/neuronal-nitric-oxide-synthase","display_name":"neuronal nitric oxide synthase","score":0.9399999976158142},{"id":"https://openalex.org/keywords/tsc2","display_name":"TSC2","score":0.9279999732971191},{"id":"https://openalex.org/keywords/chronic-pain","display_name":"chronic pain","score":0.6650000214576721},{"id":"https://openalex.org/keywords/intrathecal-morphine","display_name":"intrathecal morphine","score":0.8059999942779541},{"id":"https://openalex.org/keywords/mtor-inhibitors","display_name":"mTOR inhibitors","score":0.8859999775886536}],"concepts":[{"id":"https://openalex.org/C2779245659","wikidata":"https://www.wikidata.org/wiki/Q1633866","display_name":"Hyperalgesia","level":4,"score":0.7565527558326721},{"id":"https://openalex.org/C2777389121","wikidata":"https://www.wikidata.org/wiki/Q81225","display_name":"Morphine","level":2,"score":0.7224721312522888},{"id":"https://openalex.org/C2781063702","wikidata":"https://www.wikidata.org/wiki/Q427523","display_name":"Opioid","level":3,"score":0.5899076461791992},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.48941054940223694},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4461895227432251},{"id":"https://openalex.org/C2779985140","wikidata":"https://www.wikidata.org/wiki/Q1425425","display_name":"Drug tolerance","level":2,"score":0.44306594133377075},{"id":"https://openalex.org/C98490376","wikidata":"https://www.wikidata.org/wiki/Q14876060","display_name":"mTORC1","level":4,"score":0.4121631979942322},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.38646990060806274},{"id":"https://openalex.org/C42219234","wikidata":"https://www.wikidata.org/wiki/Q131130","display_name":"Anesthesia","level":1,"score":0.37894198298454285},{"id":"https://openalex.org/C15490471","wikidata":"https://www.wikidata.org/wiki/Q2734305","display_name":"Nociception","level":3,"score":0.33739519119262695},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3226247727870941},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.24797981977462769},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.13214334845542908},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.053068727254867554},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.05262082815170288}],"mesh":[{"descriptor_ui":"D000076222","descriptor_name":"Mechanistic Target of Rapamycin Complex 1","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004305","descriptor_name":"Dose-Response Relationship, Drug","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004361","descriptor_name":"Drug Tolerance","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D006930","descriptor_name":"Hyperalgesia","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D007278","descriptor_name":"Injections, Spinal","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D009020","descriptor_name":"Morphine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D009474","descriptor_name":"Neurons","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D010146","descriptor_name":"Pain","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D013116","descriptor_name":"Spinal Cord","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D013116","descriptor_name":"Spinal Cord","qualifier_ui":"Q000196","qualifier_name":"embryology","is_major_topic":false},{"descriptor_ui":"D013154","descriptor_name":"Spleen","qualifier_ui":"Q000166","qualifier_name":"cytology","is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017207","descriptor_name":"Rats, Sprague-Dawley","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017450","descriptor_name":"Receptors, Opioid, mu","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019869","descriptor_name":"Phosphatidylinositol 3-Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D020123","descriptor_name":"Sirolimus","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D046912","descriptor_name":"Multiprotein Complexes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D049109","descriptor_name":"Cell Proliferation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D058570","descriptor_name":"TOR Serine-Threonine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D059408","descriptor_name":"Pain Management","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1172/jci70236","doi":"https://doi.org/10.1172/jci70236","is_oa":false,"landing_page_url":"https://doi.org/10.1172/jci70236","pdf_url":null,"source":{"id":"https://openalex.org/S114430552","display_name":"Journal of Clinical Investigation","issn_l":"0021-9738","issn":["0021-9738","1558-8238"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320279","host_organization_name":"American Society for Clinical Investigation","host_organization_lineage":["https://openalex.org/P4310320279"],"host_organization_lineage_names":["American Society for Clinical Investigation"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Investigation","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:2898283","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3904613","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":null,"raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:3904613","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3904613","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"J Clin Invest","raw_type":"Text"},{"id":"pmid:24382350","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/24382350","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of clinical investigation","raw_type":"Journal Article"}],"best_oa_location":{"id":"pmh:oai:europepmc.org:2898283","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3904613","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":null,"raw_type":"Text"},"sustainable_development_goals":[{"score":0.9763000011444092,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1122485289","display_name":"The Role of Endothelin-1 in Sickle Cell Disease","funder_award_id":"U01HL117684","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"},{"id":"https://openalex.org/G1195107783","display_name":null,"funder_award_id":"NS072206","funder_id":"https://openalex.org/F4320337359","funder_display_name":"National Institute of Neurological Disorders and Stroke"},{"id":"https://openalex.org/G2020963423","display_name":"Epigenetic regulation of neuropathic pain: Role of native KV1.2 antisense RNA","funder_award_id":"R01NS072206","funder_id":"https://openalex.org/F4320337359","funder_display_name":"National Institute of Neurological Disorders and Stroke"},{"id":"https://openalex.org/G2268840381","display_name":"mTOR, A new target for opioid-induced togerance and hyperalgesia","funder_award_id":"R01DA033390","funder_id":"https://openalex.org/F4320337347","funder_display_name":"National Institute on Drug Abuse"},{"id":"https://openalex.org/G30662117","display_name":null,"funder_award_id":"NS-026363","funder_id":"https://openalex.org/F4320337359","funder_display_name":"National Institute of Neurological Disorders and Stroke"},{"id":"https://openalex.org/G5680124357","display_name":null,"funder_award_id":"DA033390","funder_id":"https://openalex.org/F4320337347","funder_display_name":"National Institute on Drug Abuse"},{"id":"https://openalex.org/G6650670331","display_name":null,"funder_award_id":"HL117684","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"},{"id":"https://openalex.org/G6703729172","display_name":"Injury-Induced Pain: Chemical Modulation of Nociceptors","funder_award_id":"R01NS026363","funder_id":"https://openalex.org/F4320337359","funder_display_name":"National Institute of Neurological Disorders and Stroke"},{"id":"https://openalex.org/G8553233607","display_name":null,"funder_award_id":"31171070","funder_id":"https://openalex.org/F4320332505","funder_display_name":"U.S. Public Health Service"}],"funders":[{"id":"https://openalex.org/F4320306590","display_name":"Rita Allen Foundation","ror":"https://ror.org/0515k5w36"},{"id":"https://openalex.org/F4320312581","display_name":"Rutgers, The State University of New Jersey","ror":null},{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320332505","display_name":"U.S. Public Health Service","ror":"https://ror.org/05xf94514"},{"id":"https://openalex.org/F4320337338","display_name":"National Heart, Lung, and Blood Institute","ror":"https://ror.org/012pb6c26"},{"id":"https://openalex.org/F4320337347","display_name":"National Institute on Drug Abuse","ror":"https://ror.org/00fq5cm18"},{"id":"https://openalex.org/F4320337359","display_name":"National Institute of Neurological Disorders and Stroke","ror":"https://ror.org/01s5ya894"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":58,"referenced_works":["https://openalex.org/W1540277158","https://openalex.org/W1554769608","https://openalex.org/W1625856702","https://openalex.org/W1966901093","https://openalex.org/W1969537866","https://openalex.org/W1972467982","https://openalex.org/W1974022382","https://openalex.org/W1974642290","https://openalex.org/W1975693853","https://openalex.org/W1979297235","https://openalex.org/W1981474992","https://openalex.org/W1982912226","https://openalex.org/W1984736455","https://openalex.org/W1985467148","https://openalex.org/W1989555351","https://openalex.org/W1989875371","https://openalex.org/W1997117033","https://openalex.org/W2000873101","https://openalex.org/W2008301670","https://openalex.org/W2011282245","https://openalex.org/W2014089147","https://openalex.org/W2021440104","https://openalex.org/W2026819031","https://openalex.org/W2033852424","https://openalex.org/W2041811289","https://openalex.org/W2050601812","https://openalex.org/W2060146354","https://openalex.org/W2060424507","https://openalex.org/W2061480898","https://openalex.org/W2062728888","https://openalex.org/W2065950517","https://openalex.org/W2066442640","https://openalex.org/W2068936181","https://openalex.org/W2070158337","https://openalex.org/W2075486656","https://openalex.org/W2077343488","https://openalex.org/W2079650065","https://openalex.org/W2080451230","https://openalex.org/W2086990722","https://openalex.org/W2089865983","https://openalex.org/W2094941511","https://openalex.org/W2116412341","https://openalex.org/W2118187735","https://openalex.org/W2124507412","https://openalex.org/W2124673849","https://openalex.org/W2143034003","https://openalex.org/W2144099695","https://openalex.org/W2144694293","https://openalex.org/W2160112211","https://openalex.org/W2161551303","https://openalex.org/W2162739063","https://openalex.org/W2163382569","https://openalex.org/W2167436769","https://openalex.org/W2171620312","https://openalex.org/W2320529806","https://openalex.org/W2390022310","https://openalex.org/W4238102997","https://openalex.org/W4302414272"],"related_works":["https://openalex.org/W2346149173","https://openalex.org/W2412213312","https://openalex.org/W2904560729","https://openalex.org/W2102247629","https://openalex.org/W2972843299","https://openalex.org/W2901952902","https://openalex.org/W7030095454","https://openalex.org/W4390223702","https://openalex.org/W2075486656","https://openalex.org/W2763620451"],"abstract_inverted_index":{"The":[0],"development":[1],"of":[2,47,88,108,120,191],"opioid-induced":[3],"analgesic":[4],"tolerance":[5,30,90,175,193],"and":[6,31,75,86,91,118,151,172,176],"hyperalgesia":[7],"is":[8],"a":[9],"clinical":[10],"challenge":[11],"for":[12,187],"managing":[13],"chronic":[14,195],"pain.":[15],"Adaptive":[16],"changes":[17,38,171],"in":[18,21,57,111,130,165,194],"protein":[19,53,116,169],"translation":[20,112,170],"the":[22,106,141,159],"nervous":[23],"system":[24],"are":[25],"thought":[26],"to":[27,105],"promote":[28],"opioid":[29,73,161,192],"hyperalgesia;":[32],"however,":[33],"how":[34],"opioids":[35],"drive":[36],"such":[37],"remains":[39],"elusive.":[40],"Here,":[41],"we":[42],"report":[43],"that":[44,181],"mammalian":[45],"target":[46],"rapamycin":[48],"(mTOR),":[49],"which":[50],"governs":[51],"most":[52],"translation,":[54],"was":[55,69],"activated":[56],"rat":[58],"spinal":[59,135,153,168],"dorsal":[60,131],"horn":[61],"neurons":[62],"after":[63],"repeated":[64],"intrathecal":[65],"morphine":[66,89,146,174],"injections.":[67],"Activation":[68],"triggered":[70],"through":[71],"\u03bc":[72,160],"receptor":[74],"mediated":[76],"by":[77,138],"intracellular":[78],"PI3K/Akt.":[79],"Spinal":[80],"mTOR":[81,136,182],"inhibition":[82],"blocked":[83],"both":[84],"induction":[85],"maintenance":[87],"hyperalgesia,":[92],"without":[93],"affecting":[94],"basal":[95],"pain":[96,149,196],"perception":[97],"or":[98],"locomotor":[99],"functions.":[100],"These":[101,178],"effects":[102],"were":[103],"attributed":[104],"attenuation":[107],"morphine-induced":[109,167],"increases":[110],"initiation":[113],"activity,":[114],"nascent":[115],"synthesis,":[117],"expression":[119],"some":[121],"known":[122],"key":[123],"tolerance-associated":[124],"proteins,":[125],"including":[126],"neuronal":[127],"NOS":[128],"(nNOS),":[129],"horn.":[132],"Moreover,":[133],"elevating":[134],"activity":[137],"knocking":[139],"down":[140],"mTOR-negative":[142],"regulator":[143],"TSC2":[144],"reduced":[145],"analgesia,":[147],"produced":[148],"hypersensitivity,":[150],"increased":[152],"nNOS":[154],"expression.":[155],"Our":[156],"findings":[157],"implicate":[158],"receptor-triggered":[162],"PI3K/Akt/mTOR":[163],"pathway":[164],"promoting":[166],"associated":[173],"hyperalgesia.":[177],"data":[179],"suggest":[180],"inhibitors":[183],"could":[184],"be":[185],"explored":[186],"prevention":[188],"and/or":[189],"reduction":[190],"management.":[197]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":10},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":8},{"year":2022,"cited_by_count":17},{"year":2021,"cited_by_count":13},{"year":2020,"cited_by_count":22},{"year":2019,"cited_by_count":23},{"year":2018,"cited_by_count":12},{"year":2017,"cited_by_count":16},{"year":2016,"cited_by_count":17},{"year":2015,"cited_by_count":21},{"year":2014,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}