{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:44:06Z","timestamp":1785825846753,"version":"3.56.0"},"reference-count":33,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["bjanaesthesia.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["British Journal of Anaesthesia"],"published-print":{"date-parts":[[2022,12]]},"DOI":"10.1016\/j.bja.2022.07.055","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T06:10:06Z","timestamp":1665641406000},"page":"959-969","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["The nonopioid cholinergic agonist GTS-21 mitigates morphine-induced aggravation of burn injury pain together with inhibition of spinal microglia activation in young rats"],"prefix":"10.1016","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9195-8991","authenticated-orcid":false,"given":"Yang","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zerong","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0331-2427","authenticated-orcid":false,"given":"Hao","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Kem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianren","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.A. Jeevendra","family":"Martyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bja.2022.07.055_bib1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1136\/ip.2007.018143","article-title":"World report on child injury prevention","volume":"14","author":"Sminkey","year":"2008","journal-title":"Inj Prev"},{"key":"10.1016\/j.bja.2022.07.055_bib2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s41038-017-0094-8","article-title":"Considerations for pediatric burn sedation and analgesia","volume":"5","author":"Fagin","year":"2017","journal-title":"Burns Trauma"},{"key":"10.1016\/j.bja.2022.07.055_bib3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/BCR.0b013e31822bef92","article-title":"Patterns of medication administration from 2001 to 2009 in the treatment of children with acute burn injuries: a multicenter study","volume":"32","author":"Stoddard","year":"2011","journal-title":"J\u00a0Burn Care Res"},{"key":"10.1016\/j.bja.2022.07.055_bib4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s41038-018-0134-z","article-title":"Long-term mental health outcomes after unintentional burns sustained during childhood: a retrospective cohort study","volume":"6","author":"Duke","year":"2018","journal-title":"Burns Trauma"},{"key":"10.1016\/j.bja.2022.07.055_bib5","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1038\/s41390-021-01383-z","article-title":"Postoperative breakthrough pain in paediatric cardiac surgery not reduced by increased morphine concentrations","volume":"90","author":"de Hoogd","year":"2021","journal-title":"Pediatr Res"},{"key":"10.1016\/j.bja.2022.07.055_bib6","doi-asserted-by":"crossref","DOI":"10.1093\/burnst\/tkaa011","article-title":"Prevalence and associated predictors for patients developing chronic neuropathic pain following burns","volume":"8","author":"Klifto","year":"2020","journal-title":"Burns Trauma"},{"key":"10.1016\/j.bja.2022.07.055_bib7","doi-asserted-by":"crossref","first-page":"67 e1","DOI":"10.1016\/j.jhsa.2020.07.001","article-title":"Chronic neuropathic pain following hand burns: etiology, treatment, and long-term outcomes","volume":"46","author":"Klifto","year":"2021","journal-title":"J\u00a0Hand Surg Am"},{"key":"10.1016\/j.bja.2022.07.055_bib8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1056\/NEJMra1800222","article-title":"Opioid tolerance in critical illness","volume":"380","author":"Martyn","year":"2019","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.bja.2022.07.055_bib9","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/ALN.0000000000002495","article-title":"Morphine exacerbates postfracture nociceptive sensitization, functional Impairment, and microglial activation in mice","volume":"130","author":"Li","year":"2019","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2022.07.055_bib10","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1097\/ALN.0000000000000422","article-title":"Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury","volume":"121","author":"Ueda","year":"2014","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2022.07.055_bib11","first-page":"119","article-title":"Unilateral focal burn injury is followed by long-lasting bilateral allodynia and neuronal hyperexcitability in spinal cord dorsal horn","volume":"11","author":"Chang","year":"2010","journal-title":"J\u00a0Pain"},{"key":"10.1016\/j.bja.2022.07.055_bib12","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1213\/ANE.0000000000005274","article-title":"Nonopioid GTS-21 mitigates burn injury pain in rats by decreasing spinal cord inflammatory responses","volume":"132","author":"Zhou","year":"2021","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2022.07.055_bib13","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/ALN.0000000000000559","article-title":"Acute and perioperative care of the burn-injured patient","volume":"122","author":"Bittner","year":"2015","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2022.07.055_bib14","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1089\/ars.2012.4671","article-title":"The microglial alpha 7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2","volume":"19","author":"Parada","year":"2013","journal-title":"Antioxid Redox Signal"},{"key":"10.1016\/j.bja.2022.07.055_bib15","article-title":"Activation of alpha-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress","volume":"9","author":"Han","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.bja.2022.07.055_bib16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.brainres.2019.03.016","article-title":"Activation of alpha 7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia","volume":"1715","author":"Ji","year":"2019","journal-title":"Brain Res"},{"key":"10.1016\/j.bja.2022.07.055_bib17","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1213\/01.ANE.0000152192.23851.40","article-title":"Age-dependent morphine tolerance development in the rat","volume":"100","author":"Wang","year":"2005","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2022.07.055_bib18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/PCC.0b013e318253c80e","article-title":"Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study","volume":"14","author":"Anand","year":"2013","journal-title":"Pediatr Crit Care Med"},{"key":"10.1016\/j.bja.2022.07.055_bib19","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neuroscience.2013.09.010","article-title":"Distinct activation profiles in microglia of different ages: a systematic study in isolated embryonic to aged microglial cultures","volume":"254","author":"Lai","year":"2013","journal-title":"Neuroscience"},{"key":"10.1016\/j.bja.2022.07.055_bib20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1744-8069-5-70","article-title":"Differential regulation of immune responses and macrophage\/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury","volume":"5","author":"Vega-Avelaira","year":"2009","journal-title":"Mol Pain"},{"key":"10.1016\/j.bja.2022.07.055_bib21","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.bbi.2006.10.007","article-title":"Age-related changes in the spinal cord microglial and astrocytic response profile to nerve injury","volume":"21","author":"Vega-Avelaira","year":"2007","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.bja.2022.07.055_bib22","first-page":"624","article-title":"The laboratory rat: relating its age with human's","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int J Prev Med"},{"key":"10.1016\/j.bja.2022.07.055_bib23","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1213\/ANE.0000000000004033","article-title":"Microglial modulation as a target for chronic pain: from the bench to the bedside and back","volume":"128","author":"Haight","year":"2019","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2022.07.055_bib24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/ALN.0000000000002130","article-title":"Neuroinflammation and central sensitization in chronic and widespread pain","volume":"129","author":"Ji","year":"2018","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2022.07.055_bib25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuroscience.2016.07.026","article-title":"The development of the nociceptive brain","volume":"338","author":"Verriotis","year":"2016","journal-title":"Neuroscience"},{"issue":"Suppl 2","key":"10.1016\/j.bja.2022.07.055_bib26","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1111\/j.1526-4637.2011.01311.x","article-title":"The effects of age on pain sensitivity: preclinical studies","volume":"13","author":"Yezierski","year":"2012","journal-title":"Pain Med"},{"key":"10.1016\/j.bja.2022.07.055_bib27","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/SHK.0000000000000729","article-title":"Prevention of burn-induced inflammatory responses and muscle wasting by GTS-21, a specific agonist for alpha 7 nicotinic ccetylcholine receptors","volume":"47","author":"Kashiwagi","year":"2017","journal-title":"Shock"},{"key":"10.1016\/j.bja.2022.07.055_bib28","doi-asserted-by":"crossref","first-page":"aaf1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: a program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.bja.2022.07.055_bib29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12974-021-02103-4","article-title":"Systemic administration of beta-glucan induces immune training in microglia","volume":"18","author":"Heng","year":"2021","journal-title":"J\u00a0Neuroinflammation"},{"key":"10.1016\/j.bja.2022.07.055_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.104928","article-title":"Opioid system influences gut-brain axis: dysbiosis and related alterations","volume":"159","author":"Rueda-Ruzafa","year":"2020","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.bja.2022.07.055_bib31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/(SICI)1099-081X(199804)19:3<147::AID-BDD77>3.0.CO;2-9","article-title":"Pharmacokinetics and urinary excretion of DMXBA (GTS-21), a compound enhancing cognition","volume":"19","author":"Mahnir","year":"1998","journal-title":"Biopharm Drug Dispos"},{"key":"10.1016\/j.bja.2022.07.055_bib32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1124\/mol.65.1.56","article-title":"Hydroxy metabolites of the Alzheimer's drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21): their molecular properties, interactions with brain nicotinic receptors, and brain penetration","volume":"65","author":"Kem","year":"2004","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bja.2022.07.055_bib33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0378-4347(96)00233-2","article-title":"Simultaneous determination of GTS-21 and its metabolite in rat plasma by high-performance liquid chromatography using solid-phase extraction","volume":"686","author":"Azuma","year":"1996","journal-title":"J\u00a0Chromatogr B Biomed Appl"}],"container-title":["British Journal of Anaesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091222005037?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091222005037?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T19:04:34Z","timestamp":1757790274000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0007091222005037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["S0007091222005037"],"URL":"https:\/\/doi.org\/10.1016\/j.bja.2022.07.055","relation":{},"ISSN":["0007-0912"],"issn-type":[{"value":"0007-0912","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The nonopioid cholinergic agonist GTS-21 mitigates morphine-induced aggravation of burn injury pain together with inhibition of spinal microglia activation in young rats","name":"articletitle","label":"Article Title"},{"value":"British Journal of Anaesthesia","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bja.2022.07.055","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 British Journal of Anaesthesia. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}