{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:53:17Z","timestamp":1778932397517,"version":"3.51.4"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2016-06576"],"award-info":[{"award-number":["2016-06576"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2021-02926"],"award-info":[{"award-number":["2021-02926"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["PGS-D"],"award-info":[{"award-number":["PGS-D"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013200","name":"Government of Alberta","doi-asserted-by":"publisher","award":["Alberta Graduate Excellence Scholarship"],"award-info":[{"award-number":["Alberta Graduate Excellence Scholarship"]}],"id":[{"id":"10.13039\/100013200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The use of chloral hydrate as a sole maintenance anesthetic agent in rodent research has been controversial due to statements made in reference literature conflicting with results of primary research studies regarding its analgesic efficacy, and because of its associated tissue damage when administered intraperitoneally.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Our aim was to assess the analgesic efficacy of chloral hydrate using an intravenous (i.v.) route of administration, in order to prevent the local tissue irritation or ileus that has been previously reported using intraperitoneal (i.p.) routes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We measured tail withdrawal latencies to a nociceptive thermal stimulus (infrared beam) in Sprague-Dawley rats\u2013first when awake (unanesthetized), and then subsequently during i.v. chloral hydrate anesthesia. During anesthesia we also measured ongoing heart and respiration rates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Withdrawal latencies during chloral hydrate anesthesia were significantly higher, and often maximal, indicating a robust analgesic effect. Importantly, both respiration and heart rate remained unchanged following exposure to the nociceptive stimulus, and were comparable to values observed under other anesthetics and during natural sleep.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Together with previous studies, these results demonstrate that i.v. chloral hydrate provides excellent anesthetic depth and analgesic efficacy for surgical manipulations in rats.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0286504","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T20:51:51Z","timestamp":1687639911000},"page":"e0286504","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Intravenous chloral hydrate anesthesia provides appropriate analgesia for surgical interventions in male Sprague-Dawley rats"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7532-2325","authenticated-orcid":true,"given":"Rachel","family":"Ward-Flanagan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-8110","authenticated-orcid":true,"given":"Clayton T.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"issue":"27","key":"pone.0286504.ref001","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1056\/NEJMra0808281","article-title":"General anesthesia, sleep, and coma","volume":"363","author":"EN Brown","year":"2010","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0286504.ref002","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/ALN.0b013e3181a8617e","article-title":"Chloral Hydrate Is Not Acceptable for Anesthesia or Euthanasia of Small Animals","volume":"111","author":"G Baxter Mark","year":"2009","journal-title":"Anesthesiology"},{"issue":"3","key":"pone.0286504.ref003","first-page":"210","article-title":"A review of laboratory animal anesthesia with chloral hydrate and chloralose","volume":"43","author":"J Silverman","year":"1993","journal-title":"Lab Anim Sci"},{"issue":"2","key":"pone.0286504.ref004","first-page":"238","article-title":"Adynamic ileus in the rat induced by chloral hydrate","volume":"27","author":"RW Fleischman","year":"1977","journal-title":"Lab Anim Sci"},{"key":"pone.0286504.ref005","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/B978-0-12-800036-6.00002-8","volume-title":"Laboratory Animal Anaesthesia (Fourth Edition).","author":"P Flecknell","year":"2016"},{"key":"pone.0286504.ref006","volume-title":"Veterinary anaesthesia","author":"C Hall","year":"2001","edition":"1"},{"issue":"17","key":"pone.0286504.ref007","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.lfs.2006.05.019","article-title":"Differential effects of chloral hydrate- and ketamine\/xylazine-induced anesthesia by the s.c. route","volume":"79","author":"SF Rodrigues","year":"2006","journal-title":"Life Sciences"},{"issue":"3","key":"pone.0286504.ref008","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1258\/002367793780745471","article-title":"Anaesthetic effects of chloral hydrate, pentobarbitone and urethane in adult male rats.","volume":"27","author":"KJ Field","year":"1993","journal-title":"Lab Anim"},{"issue":"6","key":"pone.0286504.ref009","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1097\/00001756-200205070-00023","article-title":"Trichloroethanol alters action potentials in a subgroup of primary sensory neurones","volume":"13","author":"M Gruss","year":"2002","journal-title":"Neuroreport"},{"issue":"3","key":"pone.0286504.ref010","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1046\/j.1471-4159.2003.01716.x","article-title":"Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293\u2010hP2X3 cells and their inhibition by ethanol and trichloroethanol","volume":"85","author":"W Fischer","year":"2003","journal-title":"Journal of neurochemistry"},{"issue":"4","key":"pone.0286504.ref011","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/cne.21685","article-title":"Role of endogenous sleep-wake and analgesic systems in anesthesia","volume":"508","author":"J Lu","year":"2008","journal-title":"J Comp Neurol"},{"key":"pone.0286504.ref012","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.brainres.2016.04.019","article-title":"Towards optimized anesthesia protocols for stereotactic surgery in rats: Analgesic, stress and general health effects of injectable anesthetics. A comparison of a recommended complete reversal anesthesia with traditional chloral hydrate monoanesthesia","volume":"1642","author":"C H\u00fcske","year":"2016","journal-title":"Brain research"},{"issue":"61","key":"pone.0286504.ref013","first-page":"3393","article-title":"Chronic constriction of the sciatic nerve and pain hypersensitivity testing in rats","author":"PJ Austin","year":"2012","journal-title":"J Vis Exp"},{"issue":"4","key":"pone.0286504.ref014","first-page":"597","article-title":"Animal Models of Nociception.","volume":"53","author":"D Le Bars","year":"2001","journal-title":"Pharmacological Reviews."},{"issue":"10","key":"pone.0286504.ref015","doi-asserted-by":"crossref","first-page":"e0258939","DOI":"10.1371\/journal.pone.0258939","article-title":"Long-term stability of physiological signals within fluctuations of brain state under urethane anesthesia","volume":"16","author":"NRG Silver","year":"2021","journal-title":"PLOS ONE"},{"issue":"11","key":"pone.0286504.ref016","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1523\/JNEUROSCI.3581-13.2014","article-title":"Lack of Respiratory Coupling with Neocortical and Hippocampal Slow Oscillations","volume":"34","author":"J Viczko","year":"2014","journal-title":"The Journal of Neuroscience"},{"key":"pone.0286504.ref017","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2017.00284","article-title":"Methods Used to Evaluate Pain Behaviors in Rodents","volume":"10","author":"JR Deuis","year":"2017","journal-title":"Frontiers in Molecular Neuroscience"},{"issue":"2","key":"pone.0286504.ref018","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0006-8993(86)91138-8","article-title":"III. Comparison of the antinociceptive action of mu and delta opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique","volume":"372","author":"TS Jensen","year":"1986","journal-title":"Brain research"},{"issue":"5","key":"pone.0286504.ref019","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.sleep.2010.02.002","article-title":"Cellular and chemical neuroscience of mammalian sleep.","volume":"11","author":"S Datta","year":"2010","journal-title":"Sleep Medicine"},{"issue":"3","key":"pone.0286504.ref020","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0952-8180(01)00384-1","article-title":"Changes in heart rate variability in sevoflurane and nitrous oxide anesthesia: effects of respiration and depth of anesthesia","volume":"14","author":"I Nakatsuka","year":"2002","journal-title":"Journal of Clinical Anesthesia"},{"issue":"3","key":"pone.0286504.ref021","first-page":"437","article-title":"Effects of intrathecal mu, delta, and kappa agonists on thermally evoked cardiovascular and nociceptive reflexes in halothane-anesthetized rats.","volume":"80","author":"H Nagasaka","year":"1995","journal-title":"Anesthesia & Analgesia."},{"issue":"7","key":"pone.0286504.ref022","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.3390\/ijms23073608","article-title":"A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats","volume":"23","author":"R Ward-Flanagan","year":"2022","journal-title":"International Journal of Molecular Sciences"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0286504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T20:52:10Z","timestamp":1687639930000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0286504"}},"subtitle":[],"editor":[{"given":"Uwe","family":"Rudolph","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,6,23]]},"references-count":22,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0286504","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,23]]}}}