Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling

Vetter, Irina, Touska, Filip, Hess, Andreas, Hinsbey, Rachel, Sattler, Simon, Lampert, Angelika, Sergejeva, Marina, Sharov, Anastasia, Collins, Lindon S., Eberhardt, Mirjam, Engel, Matthias, Cabot, Peter J., Wood, John N., Vlachova, Viktorie, Reeh, Peter W., Lewis, Richard J. and Zimmermann, Katharina (2012) Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling. EMBO Journal, 31 19: 3795-3808. doi:10.1038/emboj.2012.207

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Author Vetter, Irina
Touska, Filip
Hess, Andreas
Hinsbey, Rachel
Sattler, Simon
Lampert, Angelika
Sergejeva, Marina
Sharov, Anastasia
Collins, Lindon S.
Eberhardt, Mirjam
Engel, Matthias
Cabot, Peter J.
Wood, John N.
Vlachova, Viktorie
Reeh, Peter W.
Lewis, Richard J.
Zimmermann, Katharina
Title Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling
Journal name EMBO Journal   Check publisher's open access policy
ISSN 0261-4189
Publication date 2012-10
Sub-type Article (original research)
DOI 10.1038/emboj.2012.207
Volume 31
Issue 19
Start page 3795
End page 3808
Total pages 14
Place of publication London, United Kingdom
Publisher Nature
Collection year 2013
Language eng
Abstract Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by targeting specific unmyelinated and myelinated primary sensory neurons. These include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously expressed TRPA1, but when co-expressed with Na v channels, sodium channel activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that is responsible for the development of cold allodynia, as evidenced by a large reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1-deficient mice, confirming an important role for TRPA1 in the pathogenesis of cold allodynia.
Keyword Ciguatoxin
Cold allodynia
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 31 July 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Pharmacy Publications
Institute for Molecular Bioscience - Publications
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