Axonal excitability changes and acute symptoms of oxaliplatin treatment: In vivo evidence for slowed sodium channel inactivation |
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Authors: | Rikke Heide Hugh Bostock Lise Ventzel Peter Grafe Joseph Bergmans Anders Fuglsang-Frederiksen Nanna B. Finnerup Hatice Tankisi |
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Affiliation: | 1. Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark;2. Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark;3. Institute of Neurology, Queen Square House, London, United Kingdom;4. Department of Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark;5. Institute of Physiology, Ludwig-Maximilians University Munich, Munich, Germany;6. Laboratory of Clinical Neurophysiology, Faculty of Medicine, University of Louvain, Brussels, Belgium |
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Abstract: | ObjectiveNeurotoxicity is the most frequent dose-limiting side effect of the anti-cancer agent oxaliplatin, but the mechanisms are not well understood. This study used nerve excitability testing to investigate the pathophysiology of the acute neurotoxicity.MethodsQuestionnaires, quantitative sensory tests, nerve conduction studies and nerve excitability testing were undertaken in 12 patients with high-risk colorectal cancer treated with adjuvant oxaliplatin and in 16 sex- and age-matched healthy controls. Examinations were performed twice for patients: once within 3?days after oxaliplatin treatment (post-infusion examination) and once shortly before the following treatment (recovery examination).ResultsThe most frequent post-infusion symptoms were tingling paresthesias and cold allodynia. The most prominent nerve excitability change was decreased superexcitability of motor axons which correlated with the average intensity of abnormal sensations (Spearman Rho?=?0.80, p?.01). The motor nerve excitability changes were well modeled by a slowing of sodium channel inactivation, and were proportional to dose/m2 with a half-life of about 10d.ConclusionsOxaliplatin induces reversible slowing of sodium channel inactivation in motor axons, and these changes are closely related to the reversible cold allodynia. However, further studies are required due to small sample size in this study.SignificanceNerve excitability data provide an index of sodium channel dysfunction: an objective biomarker of acute oxaliplatin neurotoxicity. |
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Keywords: | Nerve excitability testing Chemotherapy Neuropathy Quantitative sensory tests Oxaliplatin toxicity Sodium channel dysfunction |
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