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A polyamine-deficient diet prevents oxaliplatin-induced acute cold and mechanical hypersensitivity in rats.

Authors: Ferrier, Jérémy  Bayet-Robert, Mathilde  Pereira, Bruno  Daulhac, Laurence  Eschalier, Alain  Pezet, Denis  Moulinoux, Jacques-Philippe  Balayssac, David 
Citation: Ferrier J, etal., PLoS One. 2013 Oct 30;8(10):e77828. doi: 10.1371/journal.pone.0077828. eCollection 2013.
Pubmed: (View Article at PubMed) PMID:24204988
DOI: Full-text: DOI:10.1371/journal.pone.0077828


BACKGROUND: Oxaliplatin is an anticancer drug used for the treatment of advanced colorectal cancer, but it can also cause painful peripheral neuropathies. The pathophysiology of these neuropathies has not been yet fully elucidated, but may involve spinal N-methyl-D-aspartate (NMDA) receptors, particularly the NR2B subunit. As polyamines are positive modulators of NMDA-NR2B receptors and mainly originate from dietary intake, the modulation of polyamines intake could represent an interesting way to prevent/modulate neuropathic pain symptoms by opposing glutamate neurotransmission.
METHODS: The effect of a polyamine deficient diet was investigated in an animal model of oxaliplatin-induced acute pain hypersensitivity using behavioral tests (mechanical and cold hypersensitivity). The involvement of spinal glutamate neurotransmission was monitored by using a proton nuclear magnetic resonance spectroscopy based metabolomic approach and by assessing the expression and phosphorylation of the NR2B subunit of the NMDA receptor.
RESULTS: A 7-day polyamine deficient diet totally prevented oxaliplatin-induced acute cold hypersensitivity and mechanical allodynia. Oxaliplatin-induced pain hypersensitivity was not associated with an increase in NR2B subunit expression or phosphorylation, but with an increase of glutamate level in the spinal dorsal horn which was completely prevented by a polyamine deficient diet. As a validation that the oxaliplatin-induced hypersensitivity could be due to an increased activity of the spinal glutamate system, an intrathecal administration of the specific NR2B antagonist, ifenprodil, totally reversed oxaliplatin-induced mechanical and cold hypersensitivity.
CONCLUSION: A polyamine deficient diet could represent a promising and valuable nutritional therapy to prevent oxaliplatin-induced acute pain hypersensitivity.

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RGD ID: 13210755
Created: 2017-09-06
Species: All species
Last Modified: 2017-09-06
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.