Patel, R;
Brice, NL;
Lewis, RJ;
Dickenson, AH;
(2015)
Ionic Mechanisms of Spinal Neuronal Cold Hypersensitivity in Ciguatera.
European Journal of Neuroscience
, 42
(11)
pp. 3004-3011.
10.1111/ejn.13098.
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Abstract
Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. These studies for the first time examine neural substrates and molecular components of Pacific ciguatoxin-2 induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nM ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by M8-An, an antagonist of TRPM8. Both mechanical and cold hypersensitivity were completely prevented by co-injection with Nav1.8 antagonist A803467, whereas TRPA1 antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naïve rats, neither innocuous nor noxious cold evoked neuronal responses were inhibited by antagonists of Nav1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav1.8/TRPA1+ primary afferents, which could underlie cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin induced-hypersensitivity. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Ionic Mechanisms of Spinal Neuronal Cold Hypersensitivity in Ciguatera |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/ejn.13098 |
| Publisher version: | http://dx.doi.org/10.1111/ejn.13098 |
| Language: | English |
| Additional information: | © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | In vivo electrophysiology, Nav1.8, TRP channels, ciguatoxin, dorsal horn |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1473986 |
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