Analgesic treatment of ciguatoxin-induced cold allodynia

Zimmermann, Katharina, Deuis, Jennifer R., Inserra, Marco C., Collins, Lindon S., Namer, Barbara, Cabot, Peter J., Reeh, Peter W., Lewis, Richard J. and Vetter, Irina (2013) Analgesic treatment of ciguatoxin-induced cold allodynia. Pain, 154 10: 1999-2006. doi:10.1016/j.pain.2013.06.015

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Author Zimmermann, Katharina
Deuis, Jennifer R.
Inserra, Marco C.
Collins, Lindon S.
Namer, Barbara
Cabot, Peter J.
Reeh, Peter W.
Lewis, Richard J.
Vetter, Irina
Title Analgesic treatment of ciguatoxin-induced cold allodynia
Journal name Pain   Check publisher's open access policy
ISSN 0304-3959
1872-6623
Publication date 2013-10
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.pain.2013.06.015
Open Access Status File (Author Post-print)
Volume 154
Issue 10
Start page 1999
End page 2006
Total pages 8
Place of publication Amsterdam, The Netherlands
Publisher Elsevier BV
Collection year 2014
Language eng
Formatted abstract
Ciguatera, the most common form of nonbacterial ichthyosarcotoxism, is caused by consumption of fish that have bioaccumulated the polyether sodium channel activator ciguatoxin. The neurological symptoms of ciguatera include distressing, often persistent sensory disturbances such as paraesthesias and the pathognomonic symptom of cold allodynia. We show that intracutaneous administration of ciguatoxin in humans elicits a pronounced axon-reflex flare and replicates cold allodynia. To identify compounds able to inhibit ciguatoxin-induced Nav responses, we developed a novel in vitro ciguatoxin assay using the human neuroblastoma cell line SH-SY5Y. Pharmacological characterisation of this assay demonstrated a major contribution of Nav1.2 and Nav1.3, but not Nav1.7, to ciguatoxin-induced Ca2+ responses. Clinically available Nav inhibitors, as well as the Kv7 agonist flupirtine, inhibited tetrodotoxin-sensitive ciguatoxin-evoked responses. To establish their in vivo efficacy, we used a novel animal model of ciguatoxin-induced cold allodynia. However, differences in the efficacy of these compounds to reverse ciguatoxin-induced cold allodynia did not correlate with their potency to inhibit ciguatoxin-induced responses in SH-SY5Y cells or at heterologously expressed Nav1.3, Nav1.6, Nav1.7, or Na v1.8, indicating cold allodynia might be more complex than simple activation of Nav channels. These findings highlight the need for suitable animal models to guide the empiric choice of analgesics, and suggest that lamotrigine and flupirtine could be potentially useful for the treatment of ciguatera.
Keyword Allodynia
Ciguatoxin
Cold pain
Nociceptor
Peripheral
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Pharmacy Publications
Institute for Molecular Bioscience - Publications
 
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