Brain mechanisms of abnormal temperature perception in cold allodynia induced by ciguatoxin

Eisenblatter, Anneka, Lewis, Richard, Dorfler, Arnd, Forster, Clemens and Zimmermann, Katharina (2017) Brain mechanisms of abnormal temperature perception in cold allodynia induced by ciguatoxin. Annals of Neurology, 81 1: 104-116. doi:10.1002/ana.24841

Author Eisenblatter, Anneka
Lewis, Richard
Dorfler, Arnd
Forster, Clemens
Zimmermann, Katharina
Title Brain mechanisms of abnormal temperature perception in cold allodynia induced by ciguatoxin
Journal name Annals of Neurology   Check publisher's open access policy
ISSN 1531-8249
Publication date 2017-01-01
Sub-type Article (original research)
DOI 10.1002/ana.24841
Open Access Status Not yet assessed
Volume 81
Issue 1
Start page 104
End page 116
Total pages 13
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
Objective: Cold allodynia occurs as a major symptom of neuropathic pain states. It remains poorly treated with current analgesics. Ciguatoxins (CTXs), ichthyosarcotoxins that cause ciguatera, produce a large peripheral sensitization to dynamic cold stimuli in Aδ-fibers by activating sodium channels without producing heat or mechanical allodynia. We used CTXs as a surrogate model of cold allodynia to dissect the framework of cold allodynia–activated central pain pathways.

Methods: Reversible cold allodynia was induced in healthy male volunteers by shallow intracutaneous injection of low millimolar concentrations of CTX into the dorsal skin of the forefoot. Cold and warm stimuli were delivered to the treated and the control site using a Peltier-driven thermotest device. Functional magnetic resonance imaging (fMRI) scans were acquired with a 3T MRI scanner using a blood oxygen level–dependent (BOLD) protocol.

Results: The CTX-induced substantial peripheral sensitization to cooling stimuli in Aδ-fibers is particularly retrieved in BOLD changes due to dynamic temperature changes and less during constant cooling. Brain areas that responded during cold allodynia were almost always located bilaterally and appeared in the medial insula, medial cingulate cortex, secondary somatosensory cortex, frontal areas, and cerebellum. Whereas these areas also produced changes in BOLD signal during the dynamic warming stimulus on the control site, they remained silent during the warming stimuli on the injected site.

Interpretation: We describe the defining feature of the cold allodynia pain percept in the human brain and illustrate why ciguatera sufferers often report a perceptual temperature reversal.
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Institutional Status UQ

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