Premium
Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera
Author(s) -
Patel Ryan,
Brice Nicola L.,
Lewis Richard J.,
Dickenson Anthony H.
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13098
Subject(s) - allodynia , chemistry , transient receptor potential channel , trpm8 , noxious stimulus , ciguatoxin , antagonist , nociception , pharmacology , medicine , neuroscience , endocrinology , hyperalgesia , receptor , biology , biochemistry , trpv1 , fishery , fish <actinopterygii>
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. This study examined, for the first time, the 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 n m 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 6‐({2‐[2‐fluoro‐6‐(trifluoromethyl)phenoxy]‐2‐methylpropyl}carbamoyl)pyridine‐3‐carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co‐injection with the Na v 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold‐evoked neuronal responses were inhibited by antagonists of Na v 1.8, TRPA 1 or TRPM 8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold‐insensitive Na v 1.8/ TRPA 1‐positive primary afferents, which could underlie the 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.