{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:55:46Z","timestamp":1780422946160,"version":"3.54.1"},"reference-count":72,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2017,10,29]],"date-time":"2017-10-29T00:00:00Z","timestamp":1509235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT093335A1A"],"award-info":[{"award-number":["WT093335A1A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Bortezomib (Velcade\u00ae) is a breakthrough treatment for multiple myeloma, significantly improving patient survival. However, its use is limited by painful neuropathy often resulting in dose reduction\/cessation of first\u2010line treatment due to lack of treatment. The aim of this study was to characterize a clinically relevant rat model of bortezomib\u2010induced painful neuropathy, using established evoked measures and novel ethological techniques, to aid drug discovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Adult male Sprague\u2013Dawley rats were injected i.p. with 0.1 and 0.2\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> bortezomib, or its vehicle, on days 0, 3, 7 and 10. Multiple behavioural approaches were utilized: mechanical hypersensitivity, cold allodynia, heat hypersensitivity, motor co\u2010ordination, burrowing and voluntary wheel running. At maximal bortezomib\u2010induced mechanical hypersensitivity, 200\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> ethosuximide\/vehicle and 100\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> phenyl N\u2010tert\u2010butylnitrone (PBN)\/vehicle were administered i.p. in separate experiments, and mechanical hypersensitivity assessed 1, 3 and 24\u00a0h later.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Bortezomib induced dose\u2010related mechanical hypersensitivity for up to 80\u00a0days. Bortezomib induced short\u2010term cold allodynia, but no significant change in heat hypersensitivity, motor co\u2010ordination, voluntary wheel running and burrowing behaviour compared to vehicle\u2010treated controls. Systemic PBN and ethosuximide significantly ameliorated bortezomib\u2010induced mechanical hypersensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These data characterize a reproducible rat model of clinical\u2010grade bortezomib\u2010induced neuropathy demonstrating long\u2010lasting pain behaviours to evoked stimuli. Inhibition by ethosuximide and PBN suggests involvement of calcium and\/or ROS in bortezomib\u2010induced painful neuropathy. These drugs could be used as preclinical positive controls to assess novel analgesics. As ethosuximide is widely used clinically, translation to the clinic to treat bortezomib\u2010induced painful neuropathy may be possible.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14063","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T15:56:39Z","timestamp":1507046199000},"page":"4812-4825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Characterization of a rat model of bortezomib\u2010induced painful neuropathy"],"prefix":"10.1111","volume":"174","author":[{"given":"Natalie A","family":"Duggett","sequence":"first","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7129-3670","authenticated-orcid":false,"given":"Sarah J 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