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Neuroimaging Of Cold Allodynia Reveals A Central Disinhibition Mechanism Of Pain

Authors Forstenpointner J, Binder A, Maag R, Granert O, Hüllemann P, Peller M, Wasner G, Wolff S, Jansen O, Siebner HR, Baron R

Received 21 May 2019

Accepted for publication 12 September 2019

Published 11 November 2019 Volume 2019:12 Pages 3055—3066

DOI https://doi.org/10.2147/JPR.S216508

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Michael Ueberall


Julia Forstenpointner,1,2,* Andreas Binder,1,2,* Rainer Maag,1,2 Oliver Granert,2 Philipp Hüllemann,1,2 Martin Peller,2 Gunnar Wasner,1,2 Stefan Wolff,3 Olav Jansen,3 Hartwig Roman Siebner,2,4–6 Ralf Baron1,2

1Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany; 2Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany; 3Institute of Radiology and Neuroradiology, University Hospital of Schleswig-Holstein, Kiel, Germany; 4Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; 5Department of Neurology, Copenhagen University Hospital Bispebjerg, Description, Copenhagen, Denmark; 6Institute for Clinical Medicine, Faculty of Health and Clinical Sciences, University of Copenhagen, Description, Copenhagen, Denmark

*These authors contributed equally to this work

Correspondence: Julia Forstenpointner
Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus 41, Kiel 24105, Germany
Tel +49 431 500 23921
Fax +49 431 500 23914
Email julia.forstenpointner@uksh.de

Purpose: Allodynia refers to pain evoked by physiologically innocuous stimuli. It is a disabling symptom of neuropathic pain following a lesion within the peripheral or central nervous system. In fact, two different pathophysiological mechanisms of cold allodynia (ie, hypersensitivity to innocuous cold) have been proposed. The peripheral sensitization of nociceptive neurons can produce cold allodynia, which can be induced experimentally by a topical application of menthol. An alternative mechanism involves reduced inhibition of central pain processing by innocuous cold stimuli. A model to induce the latter type of allodynia is the conduction block of peripheral A-fiber input.
Patients and methods: In the presented study, functional MRI was used to analyze these two different experimental models of cold allodynia. In order to identify the underlying cerebral activation patterns of both mechanisms, the application of menthol and the induction of a mechanical A-fiber blockade were studied in healthy volunteers.
Results: The block-induced cold allodynia caused significantly stronger activation of the medial polymodal pain processing pathway, including left medial thalamus, anterior cingulate cortex, and medial prefrontal cortex. In contrast, menthol-induced cold allodynia caused significantly stronger activity of the left lateral thalamus as well as the primary and secondary somatosensory cortices, key structures of the lateral discriminative pathway of pain processing. Mean pain intensity did not differ between both forms of cold allodynia.
Conclusion: Experimental cold allodynia is mediated in different cerebral areas depending on the underlying pathophysiology. The activity pattern associated with block-induced allodynia confirms a fundamental integration between painful and non-painful temperature sensation, ie, the cold-induced inhibition of cold pain.

Keywords: A-fiber block, menthol, cold allodynia, fMRI

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