Brain Mechanisms of Abnormal Temperature Perception in Cold Allodynia induced by Ciguatoxin

Journal article

Publication Details

Author(s): Eisenblätter A, Lewis R, Dörfler A, Forster C, Zimmermann K
Journal: Annals of Neurology
Publication year: 2016
ISSN: 0364-5134


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 A?-fibers by activating sodium channels without producing heat or mechanical allodynia. We used CTXs as surrogate model of cold allodynia to dissect the framework of cold allodynia activated central pain pathways.Reversible cold allodynia was induced in healthy male volunteers by shallow intracutaneous injection of low nM 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 3 Tesla MRI scanner using a blood-oxygen-level-dependent (BOLD) protocol.The CTX-induced substantial peripheral sensitization to cooling stimuli in A?-fibers is particularly retrieved in BOLD changes due to dynamic temperature changes and less during constant cooling. Brain areas which responded during cold allodynia were always located bilateral and appeared in the medial insula, the medial cingulate cortex, the secondary somatosensory cortex, in frontal areas and the cerebellum. While these areas produced also changes in BOLD-signal during the dynamic warming stimulus on the control site they remained silent during the warming stimuli on the injected site.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. This article is protected by copyright. All rights reserved.

FAU Authors / FAU Editors

Dörfler, Arnd Prof. Dr.
Neuroradiologische Abteilung im Radiologischen Institut
Schöniger, Anneka
Radiologisches Institut
Forster, Clemens apl. Prof. Dr.
Lehrstuhl für Physiologie
Zimmermann, Katharina Prof. Dr. med.
Heisenbergprofessur für Experimentelle Schmerzforschung

External institutions with authors

University of Queensland

How to cite

Eisenblätter, A., Lewis, R., Dörfler, A., Forster, C., & Zimmermann, K. (2016). Brain Mechanisms of Abnormal Temperature Perception in Cold Allodynia induced by Ciguatoxin. Annals of Neurology.

Eisenblätter, Anneka, et al. "Brain Mechanisms of Abnormal Temperature Perception in Cold Allodynia induced by Ciguatoxin." Annals of Neurology (2016).


Last updated on 2018-10-10 at 08:23