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

Vetter I, Touska F, Heß A, Hinsbey R, Sattler S, Lampert A, Sergeeva M, Sharov A, Collins LS, Eberhardt M, Engel M, Cabot PJ, Wood JN, Vlachová V, Reeh P, Lewis RJ, Zimmermann K (2012)

Publication Language: English

Publication Type: Journal article

Publication year: 2012

Journal

Book Volume: 31

Pages Range: 3795-3808

Journal Issue: 19

DOI: 10.1038/emboj.2012.207

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. © 2012 European Molecular Biology Organization | All Rights Reserved.

Authors with CRIS profile

Involved external institutions

University of Queensland Australia (AU) University College London (UCL) United Kingdom (GB) Institute of Physiology AS CR / Fyziologický Ústav AV ČR (FGÚ) Czech Republic (CZ)

How to cite

APA:

Vetter, I., Touska, F., Heß, A., Hinsbey, R., Sattler, S., Lampert, A.,... Zimmermann, K. (2012). Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling. The EMBO Journal, 31(19), 3795-3808. https://doi.org/10.1038/emboj.2012.207

MLA:

Vetter, Irina, et al. "Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling." The EMBO Journal 31.19 (2012): 3795-3808.

BibTeX: Download