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Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors.

Descoeur J, Pereira V, Pizzoccaro A, Francois A, Ling B, Maffre V, Couette B, Busserolles J, Courteix C, Noel J, Lazdunski M, Eschalier A, Authier N, Bourinet E - EMBO Mol Med (2011)

Bottom Line: To date, pain management strategies have failed to alleviate these symptoms, hence development of adapted analgesics is needed.These symptoms are mediated by primary afferent sensory neurons expressing the thermoreceptor TRPM8.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).

View Article: PubMed Central - PubMed

Affiliation: Département de Physiologie, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.

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Effect of oxaliplatin on mechanical perception in wild type miceNumber of paw lifts out of five mechanical stimulations using von Frey filaments corresponding to innocuous (0.07 g), intermediate (0.6 g), and noxious (1.4 g) bending forces. The pain threshold is obtained for two lifts (dotted line). The measurements were done daily before treatment (day 0) and after single i.p. injection of vehicle (filled circles, n = 10) or 1, 3 or 6 mg/kg of oxaliplatin (open triangle, open square and open circle, respectively; n = 10 per group).
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fig02: Effect of oxaliplatin on mechanical perception in wild type miceNumber of paw lifts out of five mechanical stimulations using von Frey filaments corresponding to innocuous (0.07 g), intermediate (0.6 g), and noxious (1.4 g) bending forces. The pain threshold is obtained for two lifts (dotted line). The measurements were done daily before treatment (day 0) and after single i.p. injection of vehicle (filled circles, n = 10) or 1, 3 or 6 mg/kg of oxaliplatin (open triangle, open square and open circle, respectively; n = 10 per group).

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).


Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors.

Descoeur J, Pereira V, Pizzoccaro A, Francois A, Ling B, Maffre V, Couette B, Busserolles J, Courteix C, Noel J, Lazdunski M, Eschalier A, Authier N, Bourinet E - EMBO Mol Med (2011)

Effect of oxaliplatin on mechanical perception in wild type miceNumber of paw lifts out of five mechanical stimulations using von Frey filaments corresponding to innocuous (0.07 g), intermediate (0.6 g), and noxious (1.4 g) bending forces. The pain threshold is obtained for two lifts (dotted line). The measurements were done daily before treatment (day 0) and after single i.p. injection of vehicle (filled circles, n = 10) or 1, 3 or 6 mg/kg of oxaliplatin (open triangle, open square and open circle, respectively; n = 10 per group).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377073&req=5

fig02: Effect of oxaliplatin on mechanical perception in wild type miceNumber of paw lifts out of five mechanical stimulations using von Frey filaments corresponding to innocuous (0.07 g), intermediate (0.6 g), and noxious (1.4 g) bending forces. The pain threshold is obtained for two lifts (dotted line). The measurements were done daily before treatment (day 0) and after single i.p. injection of vehicle (filled circles, n = 10) or 1, 3 or 6 mg/kg of oxaliplatin (open triangle, open square and open circle, respectively; n = 10 per group).
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).

Bottom Line: To date, pain management strategies have failed to alleviate these symptoms, hence development of adapted analgesics is needed.These symptoms are mediated by primary afferent sensory neurons expressing the thermoreceptor TRPM8.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).

View Article: PubMed Central - PubMed

Affiliation: Département de Physiologie, CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.

Show MeSH
Related in: MedlinePlus