{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:52:33Z","timestamp":1791175953838,"version":"4.1.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Opiranserin, a non-opioid analgesic acting as a glycine transporter 2 inhibitor and 5-HT2A receptor antagonist, was evaluated for reducing intraoperative rescue analgesia and postoperative pain in dogs undergoing castration under isoflurane anesthesia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Eight healthy male Beagle dogs were randomized to receive a continuous rate infusion of opiranserin (5 mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7h\n                      <jats:sup>\u22121<\/jats:sup>\n                      for 1 h before induction, then 0.33 mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7h\n                      <jats:sup>\u22121<\/jats:sup>\n                      for 9 h;\n                      <jats:italic>n<\/jats:italic>\n                      = 4) or 0.9% saline (\n                      <jats:italic>n<\/jats:italic>\n                      = 4). Anesthesia was induced with alfaxalone and maintained with isoflurane (1.5% end-tidal); all dogs received meloxicam and cefazolin preoperatively, without locoregional analgesia. Hemodynamic responses (\u0394MAP, \u0394HR) were recorded across 11 surgical events; rescue remifentanil was given when both increased \u226520% from baseline. Postoperative pain was scored with the Glasgow Composite Measure Pain Scale\u2013Short Form (GCMPS-SF) from 30 min after extubation (T0) through T7, with rescue analgesia at scores \u22655. Primary outcomes were intraoperative rescue analgesia frequency and postoperative GCMPS-SF scores; secondary outcomes were intraoperative hemodynamic responses, postoperative rescue consumption, and adverse effects. Data were analyzed with Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      tests and linear mixed models with Bonferroni-adjusted comparisons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The opiranserin group required fewer intraoperative rescue interventions than the normal saline group (median 2 [2\u20132] vs. 6.5 [3\u20139];\n                      <jats:italic>p<\/jats:italic>\n                      = 0.021). GCMPS-SF scores showed significant effects of group (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.030), time (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.047), and group \u00d7 time interaction (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.034), with lower scores in the opiranserin group at T1 (adjusted\n                      <jats:italic>p<\/jats:italic>\n                      = 0.012) but not at other time points. Among secondary outcomes, significant overall effects of group were found for \u0394MAP (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.011) and \u0394HR (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.048), and of surgical event for both (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001 and\n                      <jats:italic>p<\/jats:italic>\n                      = 0.008), with no group \u00d7 event interaction; no individual event differed significantly after correction. Cumulative postoperative rescue analgesic consumption and the incidence of adverse effects did not differ between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These preliminary findings suggest that opiranserin may reduce intraoperative rescue analgesia requirements and attenuate postoperative pain in dogs, warranting confirmation in larger trials. The absence of significant adverse effects is reassuring but should be interpreted cautiously given the small sample size.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1954078","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:33:24Z","timestamp":1791174804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Perioperative analgesic effects of opiranserin in canine castration: a pilot study"],"prefix":"10.3389","volume":"13","author":[{"given":"Seongwon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seonbin","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inhyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Gyun","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1111\/jsap.13566","article-title":"2022 WSAVA guidelines for the recognition, assessment and treatment of pain","volume":"64","author":"Monteiro","year":"2023","journal-title":"J Small Anim Pract."},{"key":"B2","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","article-title":"Central sensitization: a generator of pain hypersensitivity by central neural plasticity","volume":"10","author":"Latremoliere","year":"2009","journal-title":"J Pain."},{"key":"B3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.5326\/JAAHA-MS-7292","article-title":"2022 AAHA pain management guidelines for dogs and cats","volume":"58","author":"Gruen","year":"2022","journal-title":"J Am Anim Hosp Assoc."},{"key":"B4","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/jvp.12377","article-title":"The present and future of opioid analgesics in small animal practice","volume":"40","author":"Simon","year":"2017","journal-title":"J Vet Pharmacol Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/jcph.973","article-title":"Safety, tolerability, and pharmacokinetic characteristics of a novel nonopioid analgesic, VVZ-149 injections in healthy volunteers: a first-in-class, first-in-human study","volume":"58","author":"Oh","year":"2018","journal-title":"J Clin Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"864","DOI":"10.3390\/biom11060864","article-title":"Inhibition of glycine re-uptake: a potential approach for treating pain by augmenting glycine-mediated spinal neurotransmission and blunting central nociceptive signaling","volume":"11","author":"Cioffi","year":"2021","journal-title":"Biomolecules."},{"key":"B7","doi-asserted-by":"publisher","first-page":"17448069211043965","DOI":"10.1177\/17448069211043965","article-title":"A systematic review on descending serotonergic projections and modulation of spinal nociception in chronic neuropathic pain and after spinal cord stimulation","volume":"17","author":"Heijmans","year":"2021","journal-title":"Mol Pain."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1093\/pm\/pnab066","article-title":"Role of VVZ-149, a novel analgesic molecule, in the affective component of pain: results from an exploratory proof-of-concept study of postoperative pain following laparoscopic and robotic-laparoscopic gastrectomy","volume":"22","author":"Song","year":"2021","journal-title":"Pain Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"111729","DOI":"10.1016\/j.jclinane.2024.111729","article-title":"Reduction of postoperative pain and opioid consumption by VVZ-149, first-in-class analgesic molecule: a confirmatory phase 3 trial of laparoscopic colectomy","volume":"101","author":"Lee","year":"2025","journal-title":"J Clin Anesth."},{"key":"B10","doi-asserted-by":"publisher","first-page":"101259","DOI":"10.1016\/j.vaa.2026.101259","article-title":"Effects of opiranserin (Unafra) on mechanical nociceptive thresholds in Beagle dogs: a randomized crossover study","volume":"53","author":"Kim","year":"2026","journal-title":"Vet Anaesth Analg."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.2460\/javma.2004.224.1780","article-title":"Frequency of use of various procedures, skills, and areas of knowledge among veterinarians in private small animal exclusive or predominant practice and proficiency expected of new veterinary school graduates","volume":"224","author":"Greenfield","year":"2004","journal-title":"J Am Vet Med Assoc."},{"key":"B12","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.vaa.2022.08.009","article-title":"Evaluation of the nociception\u2013antinociception balance using the parasympathetic tone activity index in dogs anaesthetized for castration","volume":"49","author":"Gavet","year":"2022","journal-title":"Vet Anaesth Analg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.2460\/ajvr.2002.63.1557","article-title":"Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs","volume":"63","author":"Budsberg","year":"2002","journal-title":"Am J Vet Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/j.1467-2995.2012.00775.x","article-title":"Intratesticular lidocaine reduces the response to surgical castration in dogs","volume":"40","author":"Huuskonen","year":"2013","journal-title":"Vet Anaesth Analg."},{"key":"B15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1017\/S096272860003178X","article-title":"Development of the short-form Glasgow Composite Measure Pain Scale (CMPS-SF) and derivation of an analgesic intervention score","volume":"16","author":"Reid","year":"2007","journal-title":"Anim Welf."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1213\/00000539-199911000-00038","article-title":"The use of a remifentanil infusion for hemodynamic control during intracranial surgery","volume":"89","author":"Gesztesi","year":"1999","journal-title":"Anesth Analg."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e20230124","DOI":"10.1590\/0103-8478cr20230020","article-title":"Remifentanil versus fentanyl as part of total intravenous anesthesia for ovariohysterectomy in dogs","volume":"54","author":"Borges Conterno","year":"2024","journal-title":"Cienc Rural."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1002\/9781119830306.ch59","article-title":"Dogs and cats","author":"Ricc\u00f3 Pereira","year":"2024"},{"key":"B19","doi-asserted-by":"publisher","first-page":"519","DOI":"10.2165\/00023210-200620060-00006","article-title":"Spotlight on remifentanil: its analgesic and sedative use in the intensive care unit","volume":"20","author":"Battershill","year":"2006","journal-title":"CNS Drugs."},{"key":"B20","first-page":"1191","article-title":"Ovariohysterectomy requires more post-operative analgesia than orchiectomy in dogs and cats","volume":"58","author":"Quarterone","year":"2017","journal-title":"Can Vet J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.3390\/ijms22052479","article-title":"Pharmacological evidence on augmented antiallodynia following systemic co-treatment with GlyT-1 and GlyT-2 inhibitors in rat neuropathic pain model","volume":"22","author":"Mohammadzadeh","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.1038\/s41467-026-69616-5","article-title":"A reversible allosteric inhibitor of GlyT2 for neuropathic pain without on-target side effects","volume":"17","author":"Chater","year":"2026","journal-title":"Nat Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3583","DOI":"10.3892\/etm.2016.3807","article-title":"The 5-HT2A receptor potassium-chloride cotransporter 2 signaling pathway in a rat incision pain model","volume":"12","author":"Dong","year":"2016","journal-title":"Exp Ther Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1016\/j.pain.2011.03.012","article-title":"Spinal 5-HT receptors that contribute to the pain-relieving effects of spinal cord stimulation in a rat model of neuropathy","volume":"152","author":"Song","year":"2011","journal-title":"Pain."},{"key":"B25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2147\/VMRR.S126469","article-title":"Spotlight on the perioperative use of maropitant citrate","volume":"8","author":"Hay","year":"2017","journal-title":"Vet Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.2460\/javma.246.3.327","article-title":"Incidence of and risk factors for postoperative regurgitation and vomiting in dogs: 244 cases (2000\u20132012)","volume":"246","author":"Davies","year":"2015","journal-title":"J Am Vet Med Assoc."},{"key":"B27","doi-asserted-by":"publisher","first-page":"739","DOI":"10.3349\/ymj.2013.54.3.739","article-title":"Effect-site concentration of remifentanil for minimizing cardiovascular changes by inhalation of desflurane","volume":"54","author":"Jeong","year":"2013","journal-title":"Yonsei Med J."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1954078\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:33:28Z","timestamp":1791174808000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1954078\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":27,"alternative-id":["10.3389\/fvets.2026.1954078"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2026.1954078","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"1954078"}}