کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6019255 | 1186547 | 2011 | 8 صفحه PDF | دانلود رایگان |
Oxaliplatin is first-line chemotherapy for colorectal cancer, but produces dose-limiting neurotoxicity. Acute neurotoxicity following infusion produces symptoms including cold-triggered fasciculations and cramps, with subsequent chronic neuropathy developing at higher cumulative doses. Axonal excitability studies were undertaken in 15 oxaliplatin-treated patients before and immediately after oxaliplatin infusion to determine whether the mechanisms underlying acute neurotoxicity altered resting membrane potential or Na+/K+ pump function. Excitability properties were assessed before and after maximal voluntary contraction (MVC) of the abductor pollicis brevis. Following oxaliplatin infusion, abnormalities developed in the recovery cycle with refractoriness markedly increased. Following activity, changes developed consistent with axonal hyperpolarization, with proportional changes pre- and post-oxaliplatin in normalized threshold. However, recovery cycle parameters following activity were significantly and disproportionally enhanced post-oxaliplatin, with partial normalization of the recovery cycle curve post-activity. Patients with the most abnormal change in the recovery cycle after infusion demonstrated the greatest changes post-contraction. Prominent abnormalities developed in Na+ channel-associated parameters in response to natural activity, without significant alteration in axonal membrane potential or Na+/K+ pump function. Findings from the present series suggest that oxaliplatin affects nerve excitability through voltage-dependent mechanisms, with specific effects mediated through axonal Na+ channel inactivation.
Research HighlightsâºOxaliplatin produces changes in Na+ channel parameters associated with inactivation âºNatural activity produced disproportionate changes in Na+ channel parameters âºHyperpolarization produced by natural activity was sufficient to normalize function âºOxaliplatin affects nerve function via voltage-dependent mechanisms
Journal: Experimental Neurology - Volume 227, Issue 1, January 2011, Pages 120-127