An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1-6 in peripheral pain pathways

Authors
Jennifer R. Deuis, Katharina Zimmermann, Andrej A. Romanovsky, et al.


Lab
University of Queenland, Australia

Journal
PAIN Volume 154, Issue 9

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.

BIOSEB Instruments Used:
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)

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