An Animal Model of Oxaliplatin-induced Cold Allodynia Reveals a Crucial Role for Nav1.6 in Peripheral Pain Pathways

Overview

Journal Pain

Specialties Neurology
Psychiatry

Date 2013 May 29

PMID 23711479

Citations 83

Authors

Jennifer R Deuis

Katharina Zimmermann

Andrej A Romanovsky

Lourival D Possani

Peter J Cabot

Richard J Lewis

Irina Vetter

Affiliations

Soon will be listed here.

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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