An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways
Deuis JR, Zimmermann K, Romanovsky AA, Possani LD, Cabot PJ, Lewis RJ, Vetter I (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Book Volume: 154
Pages Range: 1749-1757
Journal Issue: 9
DOI: 10.1016/j.pain.2013.05.032
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. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Authors with CRIS profile
Involved external institutions
University of Queensland
Australia (AU)
Dignity Health St. Joseph's Hospital and Medical Center
United States (USA) (US)
National Autonomous University of Mexico / Universidad Nacional Autónoma de México (UNAM)
Mexico (MX)
Australia (AU)
Dignity Health St. Joseph's Hospital and Medical Center
United States (USA) (US)
National Autonomous University of Mexico / Universidad Nacional Autónoma de México (UNAM)
Mexico (MX)
How to cite
APA:
Deuis, J.R., Zimmermann, K., Romanovsky, A.A., Possani, L.D., Cabot, P.J., Lewis, R.J., & Vetter, I. (2013). An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways. Pain, 154(9), 1749-1757. https://doi.org/10.1016/j.pain.2013.05.032
MLA:
Deuis, Jennifer R., et al. "An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways." Pain 154.9 (2013): 1749-1757.
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