Sensory system - page 4 Scientific Publications

Latest publication 05/24/2011

Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel e

Cold hypersensitivity is the hallmark of oxaliplatin-induced neuropathy, which develops in nearly all patients under this chemotherapy. To date,...

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    [title] => Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel e
    [paragraph] => Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors. 
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Authors
J. Descoeur, V. Pereira, A. Pizzoccaro, A. Francois, B. Ling et al. (Team of Dr Bourinet) 

 Lab
Institut de Génomique Fonctionnelle, CNRS, UMR-5203, Département de Physiologie, Montpellier, France.
Journal
EMBO Molecular Medicine
Abstract
Cold hypersensitivity is the hallmark of oxaliplatin-induced neuropathy, which develops in nearly all patients under this chemotherapy. To date, pain management strategies have failed to alleviate these symptoms, hence development of adapted analgesics is needed. Here, we report that oxaliplatin exaggerates cold perception in mice as well as in patients. 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). These findings are corroborated by the analysis of TREK1-TRAAK  mice and use of the specific HCN inhibitor ivabradine, which abolishes the oxaliplatin-induced cold hypersensibility. These results suggest that oxaliplatin exacerbates cold perception by modulating the transcription of distinct ionic conductances that together shape sensory neuron responses to cold. The translational and clinical implication of these findings would be that ivabradine may represent a tailored treatment for oxaliplatin-induced neuropathy.
BIOSEB Instruments Used
Cold Hot Plate Test (BIO-CHP),Thermal Gradient Test (BIO-GRADIENT),Thermal Place Preference, 2 Temperatures Choice Nociception Test (BIO-T2CT),Jump Test (BIO-JTET)
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For testing animal's thermal sensitivity to pain resulting from exposure to heat or cold: the Cold Hot Plate is an innovative instrument opening new investigation fields for your analgesia and nociception research, and a useful tool for analgesic drug screening using rats or mice models.

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