Channelpedia

PubMed 23711479


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1 , Nav1.6



Title: 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, Lourival D Possani, Peter J Cabot, Richard J Lewis, Irina Vetter

Journal, date & volume: Pain, 2013 Sep , 154, 1749-57

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23711479


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.