title: Oxaliplatin and axonal Na+ channel function in vivo.
abstract: OBJECTIVE
  The aim of the study was to investigate the pathophysiology of oxaliplatin-induced neurotoxicity using clinical nerve excitability techniques that provide information about axonal ion channel function.
  
  
  METHODS
  Excitability studies were combined with standard nerve conduction studies and clinical assessment in 22 patients undergoing treatment with oxaliplatin.
  
  
  RESULTS
  Excitability studies recorded before and immediately after oxaliplatin infusion for 89 treatment cycles revealed significant increases in refractoriness and relative refractory period postinfusion in all patients, consistent with an effect of oxaliplatin on axonal Na(+) channels. However, those patients that developed chronic neuropathy had significantly greater changes. Following cessation of oxaliplatin treatment, 41% of patients had persistent symptoms and nerve conduction abnormalities consistent with the development of chronic neuropathy.
  
  
  CONCLUSIONS
  The present study provides evidence that oxaliplatin-induced neurotoxicity is mediated through an effect on axonal Na(+) channels. Clinical nerve excitability techniques may prove beneficial in monitoring for early signs of neurotoxicity and in the assessment of future prophylactic therapies.
authors.affiliation: Institute of Neurological Sciences, Prince of Wales Hospital, Sydney, New South Wales, Australia.
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000328:Adult; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000503:physiopathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D011446:Prospective Studies; D015222:Sodium Channels / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D015222:Sodium Channels; D000077150:Oxaliplatin