Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors.
Bottom Line: To date, pain management strategies have failed to alleviate these symptoms, hence development of adapted analgesics is needed.Mechanistically, oxaliplatin promotes over-excitability by drastically lowering the expression of distinct potassium channels (TREK1, TRAAK) and by increasing the expression of pro-excitatory channels such as the hyperpolarization-activated channels (HCNs).The translational and clinical implication of these findings would be that ivabradine may represent a tailored treatment for oxaliplatin-induced neuropathy.
Affiliation: Département de Physiologie, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.Show MeSH
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Mentions: Along with this alteration of cold perception, we investigated whether oxaliplatin modified the mechanical tactile/pain perception. We used three von Frey filaments corresponding to innocuous, intermediate, and noxious stimulations (0.07, 0.6, and 1.4 g, respectively). Pain threshold was considered to be reached for two withdrawals out of five consecutive filament applications. Oxaliplatin treatment resulted in the development of a dose-dependent increase in nociceptive scores (Fig 2A), reflecting a mechanical allodynia (0.07 g stimulus), and a mechanical hyperalgesia (0.6 and 1.4 g).
Affiliation: Département de Physiologie, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.