{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:59:03Z","timestamp":1789567143802,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LP120200623"],"award-info":[{"award-number":["LP120200623"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020111","name":"Therapeutic Innovation Australia","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100020111","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Collaborative Research Infrastructure Strategy (NCRIS) program","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Queensland Government Smart State Research Facilities Programme","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cisplatin, which is a chemotherapy drug listed on the World Health Organisation\u2019s List of Essential Medicines, commonly induces dose-limiting side effects including chemotherapy-induced peripheral neuropathy (CIPN) that has a major negative impact on quality of life in cancer survivors. Although adjuvant drugs including anticonvulsants and antidepressants are used for the relief of CIPN, analgesia is often unsatisfactory. Herein, we used a rat model of CIPN (cisplatin) to assess the effect of a glycine transporter 2 (GlyT2) inhibitor, relative to pregabalin, duloxetine, indomethacin and vehicle. Male Sprague-Dawley rats with cisplatin-induced mechanical allodynia and mechanical hyperalgesia in the bilateral hindpaws received oral bolus doses of the GlyT2 inhibitor (3\u201330 mg\/kg), pregabalin (3\u2013100 mg\/kg), duloxetine (3\u2013100 mg\/kg), indomethacin (1\u201310 mg\/kg) or vehicle. The GlyT2 inhibitor alleviated both mechanical allodynia and hyperalgesia in the bilateral hindpaws at a dose of 10 mg\/kg, but not at higher or lower doses. Pregabalin and indomethacin induced dose-dependent relief of mechanical allodynia but duloxetine lacked efficacy. Pregabalin and duloxetine alleviated mechanical hyperalgesia in the bilateral hindpaws while indomethacin lacked efficacy. The mechanism underpinning pain relief induced by the GlyT2 inhibitor at 10 mg\/kg is likely due to increased glycinergic inhibition in the lumbar spinal cord, although the bell-shaped dose\u2013response curve warrants further translational considerations.<\/jats:p>","DOI":"10.3390\/biom11070940","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T11:01:38Z","timestamp":1624532498000},"page":"940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Assessment of the Anti-Allodynic and Anti-Hyperalgesic Efficacy of a Glycine Transporter 2 Inhibitor Relative to Pregabalin, Duloxetine and Indomethacin in a Rat Model of Cisplatin-Induced Peripheral Neuropathy"],"prefix":"10.3390","volume":"11","author":[{"given":"Andy","family":"Kuo","sequence":"first","affiliation":[{"name":"Centre for Integrated Preclinical Drug Development, Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Corradini","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH and Co. KG, 88400 Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet R.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH and Co. KG, 88400 Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2281-3734","authenticated-orcid":false,"given":"Maree T.","family":"Smith","sequence":"additional","affiliation":[{"name":"Centre for Integrated Preclinical Drug Development, Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ref_1","unstructured":"Wild, C.P., Weiderpass, E., and Stewart, B.W. (2020). 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