Title |
An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways
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Published in |
Pain (03043959), May 2013
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DOI | 10.1016/j.pain.2013.05.032 |
Pubmed ID | |
Authors |
Jennifer R. Deuis, Katharina Zimmermann, Andrej A. Romanovsky, Lourival D. Possani, Peter J. Cabot, Richard J. Lewis, Irina Vetter |
Abstract |
Cold allodynia, pain in response to cooling, occurs during or within hours of oxaliplatin infusion and is thought to arise from a direct effect of oxaliplatin on peripheral sensory neurons. To characterize the pathophysiological mechanisms underlying acute oxaliplatin-induced cold allodynia, we established a new intraplantar oxaliplatin mouse model that rapidly developed long-lasting cold allodynia mediated entirely through tetrodotoxin-sensitive Nav pathways. Using selective inhibitors and knockout animals, we found that Nav1.6 was the key isoform involved, while thermosensitive transient receptor potential channels were not involved. Consistent with a crucial role for delayed-rectifier potassium channels in excitability in response to cold, intraplantar administration of the K(+)-channel blocker 4-aminopyridine mimicked oxaliplatin-induced cold allodynia and was also inhibited by Nav1.6 blockers. Intraplantar injection of the Nav1.6 activator Cn2 elicited spontaneous pain, mechanical allodynia, and enhanced 4-aminopyridine-induced cold allodynia. These findings provide behavioural evidence for a crucial role of Nav1.6 in multiple peripheral pain pathways including cold allodynia. |
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Geographical breakdown
Country | Count | As % |
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Canada | 1 | 25% |
United Kingdom | 1 | 25% |
Unknown | 2 | 50% |
Demographic breakdown
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Members of the public | 3 | 75% |
Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
Geographical breakdown
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United Kingdom | 1 | <1% |
Unknown | 122 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 29 | 24% |
Researcher | 22 | 18% |
Student > Master | 14 | 11% |
Student > Doctoral Student | 11 | 9% |
Student > Bachelor | 9 | 7% |
Other | 17 | 14% |
Unknown | 21 | 17% |
Readers by discipline | Count | As % |
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Neuroscience | 24 | 20% |
Agricultural and Biological Sciences | 18 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 10 | 8% |
Biochemistry, Genetics and Molecular Biology | 8 | 7% |
Other | 12 | 10% |
Unknown | 25 | 20% |