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Sci Rep. 2018 Oct 10;8(1):15084. doi: 10.1038/s41598-018-33508-6.

Oxaliplatin induces pH acidification in dorsal root ganglia neurons.

Author information

1
Department of Pharmaceutical Sciences, University of Piemonte Orientale, Via Bovio 6, 28100, Novara, Italy.
2
Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900, Monza, Italy.
3
Young Against Pain Group, Monza, Italy.
4
Department of Pharmaceutical Sciences, University of Piemonte Orientale, Via Bovio 6, 28100, Novara, Italy. armando.genazzani@uniupo.it.

Abstract

Oxaliplatin induced peripheral neurotoxicity is characterized by an acute cold-induced syndrome characterized by cramps, paresthesias/dysesthesias in the distal limbs and perioral region, that develops rapidly and lasts up to one week affecting nearly all the patients as well as by long-lasting symptoms. It has been previously shown that pharmacological or genetic ablation of TRPA1 responses reduces oxaliplatin-induced peripheral neurotoxicity in mouse models. In the present report, we show that treatment with concentrations of oxaliplatin similar to those found in plasma of treated patients leads to an acidification of the cytosol of mouse dorsal root ganglia neurons in culture and this in turn is responsible for sensitization of TRPA1 channels, thereby providing a mechanistic explanation to toxicity of oxaliplatin. Reversal of the acidification indeed leads to a significantly reduced activity of TRPA1 channels. Last, acidification occurs also in vivo after a single injection of therapeutically-relevant doses of oxaliplatin.

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