{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:35:31Z","timestamp":1786988131278,"version":"build-2736575974"},"reference-count":54,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1P-01-HL-101871"],"award-info":[{"award-number":["1P-01-HL-101871"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Galleon Pharmaceuticals","award":["GP001"],"award-info":[{"award-number":["GP001"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2018,9]]},"DOI":"10.1016\/j.ejphar.2018.07.018","type":"journal-article","created":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T13:42:47Z","timestamp":1532007767000},"page":"17-29","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":49,"special_numbering":"C","title":["Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression"],"prefix":"10.1016","volume":"834","author":[{"given":"Santhosh M.","family":"Baby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan B.","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex P.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"MacFarlane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J.","family":"Teppema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2018.07.018_bib1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2174\/138920007779315026","article-title":"Influence of phenobarbital on morphine metabolism and disposition: LC-MS\/MS determination of morphine and morphine-3-glucruonide in Wistar-Kyoto rat serum, bile, and urine","volume":"8","author":"Alnouti","year":"2007","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.ejphar.2018.07.018_bib2","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1097\/00000542-199706000-00016","article-title":"Influences of morphine on the ventilatory response to isocapnic hypoxia","volume":"86","author":"Berkenbosch","year":"1997","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib3","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1113\/jphysiol.2010.187211","article-title":"Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2","volume":"588","author":"Blain","year":"2010","journal-title":"J. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib4","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1097\/ALN.0b013e31829ce4cb","article-title":"Fentanyl utility function: a risk-benefit composite of pain relief and breathing responses","volume":"119","author":"Boom","year":"2013","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2014.01.042","article-title":"Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons","volume":"1554","author":"Cai","year":"2014","journal-title":"Brain Res."},{"key":"10.1016\/j.ejphar.2018.07.018_bib6","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/bja\/aeh180","article-title":"Respiratory and haemodynamic effects of acute postoperative pain management: evidence from published data","volume":"93","author":"Cashman","year":"2004","journal-title":"Brit. J. Anaesth."},{"key":"10.1016\/j.ejphar.2018.07.018_bib7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0009-9236(03)00152-8","article-title":"Side effects of opioids during short-term administration: effect of age, gender, and race","volume":"74","author":"Cepeda","year":"2003","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.ejphar.2018.07.018_bib8","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."},{"key":"10.1016\/j.ejphar.2018.07.018_bib9","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1600-0773.1991.tb02056.x","article-title":"Morphine-6-glucuronide: receptor binding profile in bovine caudate nucleus","volume":"68","author":"Christensen","year":"1991","journal-title":"Pharmacol. Toxicol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib10","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1399-6576.1997.tb04625.x","article-title":"Morphine metabolites","volume":"41","author":"Christrup","year":"1997","journal-title":"Acta Anaesth. Scand."},{"key":"10.1016\/j.ejphar.2018.07.018_bib11","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1248\/bpb.30.2257","article-title":"Morphine inhibits erythrocyte carbonic anhydrase in vitro and in vivo","volume":"30","author":"Coban","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.ejphar.2018.07.018_bib12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3389\/fphys.2014.00302","article-title":"Evolution and physiology of neural oxygen sensing","volume":"5","author":"Costa","year":"2014","journal-title":"Front. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib13","doi-asserted-by":"crossref","first-page":"R124","DOI":"10.1152\/ajpregu.91011.2008","article-title":"Breath-to-breath hypercapnic response in neonatal rats: temperature dependency of the chemoreflexes and potential implications for breathing stability","volume":"297","author":"Cummings","year":"2009","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib14","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1097\/00000542-199804000-00009","article-title":"Sex-related differences in the influence of morphine on ventilatory control in humans","volume":"88","author":"Dahan","year":"1998","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib15","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/ALN.0b013e3181c38c25","article-title":"Incidence, reversal, and prevention of opioid-induced respiratory depression","volume":"112","author":"Dahan","year":"2010","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11011-011-9274-6","article-title":"Morphine metabolism, transport and brain disposition","volume":"27","author":"De Gregori","year":"2012","journal-title":"Metab. Brain Dis."},{"key":"10.1016\/j.ejphar.2018.07.018_bib17","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1097\/ALN.0000000000000997","article-title":"Ventilation and the response to hypercapnia after morphine in opioid-naive and opioid-tolerant rats","volume":"124","author":"Emery","year":"2016","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1600-079X.1988.tb00766.x","article-title":"Action of morphine on melatonin release in the rat","volume":"15","author":"Esposti","year":"1988","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.ejphar.2018.07.018_bib19","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1113\/jphysiol.2003.042259","article-title":"The respiratory response to carbon dioxide in humans with unilateral and bilateral resections of the carotid bodies","volume":"549","author":"Fatemian","year":"2003","journal-title":"J. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib20","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.1113\/jphysiol.2009.176875","article-title":"Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation","volume":"587","author":"Fortuna","year":"2009","journal-title":"J. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib21","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1152\/japplphysiol.01059.2009","article-title":"Contributions of central and peripheral chemoreceptors to the ventilatory response to CO2\/H+","volume":"108","author":"Forster","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib22","first-page":"477","article-title":"Morphine-6-glucuronide is more \u03bc-selective and potent in analgesic tests than morphine","volume":"328","author":"Frances","year":"1990","journal-title":"Prog. Clin. Biol. Res."},{"key":"10.1016\/j.ejphar.2018.07.018_bib23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0022-3565(25)10743-X","article-title":"Further evidence that morphine-6 betaglucuronide is a more potent opioid agonist than morphine","volume":"262","author":"Frances","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ejphar.2018.07.018_bib24","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/0006-8993(90)91416-E","article-title":"Hypercapnia depresses nociception: endogenous opioids implicated","volume":"514","author":"Gamble","year":"1990","journal-title":"Brain Res."},{"key":"10.1016\/j.ejphar.2018.07.018_bib25","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1152\/japplphysiol.01050.2013","article-title":"Essential role of hemoglobin \u03b2-93-cysteine in post-hypoxia facilitation of breathing in conscious mice","volume":"116","author":"Gaston","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.resp.2014.09.006","article-title":"Enhanced non-eupneic breathing following hypoxic, hypercapnic or hypoxic-hypercapnic gas challenges in conscious mice","volume":"204","author":"Getsy","year":"2014","journal-title":"Resp. Physiol. Neurobiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0034-5687(00)00129-8","article-title":"Signaling pathways of the acute hypoxic ventilatory response in the nucleus tractus solitarius","volume":"121","author":"Gozal","year":"2000","journal-title":"Resp. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib28","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1152\/japplphysiol.00712.2009","article-title":"Central CO2-chemoreception and integrated neural mechanisms of cardiovascular and respiratory control","volume":"108","author":"Guyenet","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib29","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4236\/ojmip.2013.33017","article-title":"Low dose morphine elicits ventilatory excitant and depressant responses in conscious rats: role of peripheral \u00b5-opioid receptors","volume":"3","author":"Henderson","year":"2013","journal-title":"OpenJ. Mol. Integr. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.resp.2013.11.005","article-title":"Role of central and peripheral opiate receptors in the effects of fentanyl on ventilation, arterial blood-gas chemistry and analgesia in conscious rats","volume":"191","author":"Henderson","year":"2014","journal-title":"Resp. Physiol. Neurobiol."},{"issue":"88","key":"10.1016\/j.ejphar.2018.07.018_bib31","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/j.1476-5381.1986.tb16263.x","article-title":"Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo","volume":"1986","author":"Kirby","year":"1986","journal-title":"Brit. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib32","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.devbrainres.2005.03.002","article-title":"Ontogeny of respiratory sensitivity and tolerance to the mu-opioid agonist fentanyl in rat","volume":"156","author":"Laferriere","year":"2005","journal-title":"Dev. Brain Res."},{"key":"10.1016\/j.ejphar.2018.07.018_bib33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1113\/jphysiol.1986.sp016272","article-title":"Restoration of hypoxic respiratory responses in the awake rat after carotid body denervation by sinus nerve section","volume":"380","author":"Martin-Body","year":"1986","journal-title":"J. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib34","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4236\/ojmip.2013.34022","article-title":"Morphine has latent deleterious effects on the ventilatory responses to a hypoxic challenge","volume":"3","author":"May","year":"2013","journal-title":"OpenJ. Mol. Integr. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib35","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4236\/ojmip.2013.33019","article-title":"Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge","volume":"3","author":"May","year":"2013","journal-title":"Open J. Mol. Integr. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1476-5381.1980.tb10939.x","article-title":"Inhibitory actions of methionine-enkephalin and morphine on the cat carotid chemoreceptors","volume":"71","author":"McQueen","year":"1980","journal-title":"Brit. J. Pharmacol."},{"issue":"37","key":"10.1016\/j.ejphar.2018.07.018_bib37","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0896-6273(03)00092-8","article-title":"Opioid-induced quantal slowing reveals dual networks for respiratory rhythm generation","volume":"2003","author":"Mellen","year":"2003","journal-title":"Neuron"},{"key":"10.1016\/j.ejphar.2018.07.018_bib38","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/0306-3623(94)00215-9","article-title":"A non-invasive method for distinguishing central from peripheral nervous system effect of respiratory depressant drugs in conscious rats","volume":"26","author":"Murphy","year":"1995","journal-title":"Gen. Pharmacol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib39","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.resp.2012.11.009","article-title":"Ventilatory responses during and following exposure to a hypoxic challenge in conscious mice deficient or null in S-nitrosoglutathione reductase","volume":"185","author":"Palmer","year":"2013","journal-title":"Resp. Physiol. Neurobiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib40","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0304-3959(91)90170-3","article-title":"Morphine-6-glucuronide: effects on ventilation in normal volunteers","volume":"45","author":"Peat","year":"1991","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2018.07.018_bib41","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1469-7793.2000.t01-4-00493.x","article-title":"Ventilatory and central neurochemical reorganisation of O2 chemoreflex after carotid sinus nerve transection in rat","volume":"522","author":"Roux","year":"2000","journal-title":"J. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib42","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1097\/00000542-199905000-00017","article-title":"Sex differences in morphine-induced ventilatory depression reside within the peripheral chemoreflex loop","volume":"90","author":"Sarton","year":"1999","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib43","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cellsig.2005.01.004","article-title":"Molecular responses to acidosis of central chemosensitive neurons in brain","volume":"17","author":"Shimokawa","year":"2005","journal-title":"Cell Signal."},{"key":"10.1016\/j.ejphar.2018.07.018_bib44","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1164\/ajrccm\/142.4.895","article-title":"Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression","volume":"142","author":"Shook","year":"1990","journal-title":"Am. Rev. Resp. Dis."},{"issue":"47","key":"10.1016\/j.ejphar.2018.07.018_bib45","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/0024-3205(90)90619-3","article-title":"Morphine-3-glucuronide: a potent antagonist of morphine analgesia","volume":"1990","author":"Smith","year":"1990","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2018.07.018_bib46","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1440-1681.2008.05019.x","article-title":"Antinociception versus serum concentration relationships following acute administration of intravenous morphine in male and female Sprague-Dawley rats: differences between the tail flick and hot plate nociceptive tests","volume":"36","author":"South","year":"2009","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib47","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.amjsurg.2005.07.015","article-title":"Postoperative day one: a high risk period for respiratory events","volume":"190","author":"Taylor","year":"2005","journal-title":"Am. J. Surg."},{"issue":"2 Suppl.","key":"10.1016\/j.ejphar.2018.07.018_bib48","doi-asserted-by":"crossref","first-page":"S133","DOI":"10.36076\/ppj.2008\/11\/S133","article-title":"Opioid pharmacology","volume":"11","author":"Trescot","year":"2008","journal-title":"Pain. Physician"},{"key":"10.1016\/j.ejphar.2018.07.018_bib49","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1046\/j.1600-079X.2003.00094.x","article-title":"Melatonin attenuates rat carotid chemoreceptor response to hypercapnic acidosis","volume":"36","author":"Tjong","year":"2004","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.ejphar.2018.07.018_bib50","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.resp.2013.02.028","article-title":"Co-activation of \u03bc- and \u03b4-opioid receptors elicits tolerance to morphine-induced ventilatory depression via generation of peroxynitrite","volume":"186","author":"Young","year":"2013","journal-title":"Resp. Physiol. Neurobiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib51","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/01.anes.0000270760.46821.67","article-title":"Activation of opioid mu-receptors in caudal medullary raphe region inhibits the ventilatory response to hypercapnia in anesthetized rats","volume":"107","author":"Zhang","year":"2007","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib52","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.resp.2009.07.015","article-title":"Opioid mu-receptors in medullary raphe region affect the hypoxic ventilation in anesthetized rats","volume":"168","author":"Zhang","year":"2009","journal-title":"Resp. Physiol. Neurobiol."},{"key":"10.1016\/j.ejphar.2018.07.018_bib53","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/ALN.0b013e318224cc1f","article-title":"Activation of opioid \u03bc-receptors in the commissural subdivision of the nucleus tractus solitarius abolishes the ventilatory response to hypoxia in anesthetized rats","volume":"115","author":"Zhang","year":"2011","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2018.07.018_bib54","first-page":"60","article-title":"Effects of morphine on the control of the cardiovascular system by the carotid-sinus-reflex and by the carotid chemoreflex","volume":"32","author":"Zimpfer","year":"1983","journal-title":"Anaesthesist"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299918303820?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299918303820?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T18:17:21Z","timestamp":1751739441000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299918303820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9]]},"references-count":54,"alternative-id":["S0014299918303820"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2018.07.018","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2018,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2018.07.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}