Spinal fMRI Reveals Decreased Descending Inhibition during Secondary Mechanical Hyperalgesia

Mechanical hyperalgesia is one distressing symptom of neuropathic pain which is explained by central sensitization of the nociceptive system. This sensitization can be induced experimentally with the heat/capsaicin sensitization model. The aim was to investigate and compare spinal and supraspinal ac...

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Published inPloS one Vol. 9; no. 11; p. e112325
Main Authors Rempe, Torge, Wolff, Stephan, Riedel, Christian, Baron, Ralf, Stroman, Patrick W., Jansen, Olav, Gierthmühlen, Janne
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 05.11.2014
Public Library of Science (PLoS)
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ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0112325

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Summary:Mechanical hyperalgesia is one distressing symptom of neuropathic pain which is explained by central sensitization of the nociceptive system. This sensitization can be induced experimentally with the heat/capsaicin sensitization model. The aim was to investigate and compare spinal and supraspinal activation patterns of identical mechanical stimulation before and after sensitization using functional spinal magnetic resonance imaging (spinal fMRI). Sixteen healthy subjects (6 female, 10 male, mean age 27.2 ± 4.0 years) were investigated with mechanical stimulation of the C6 dermatome of the right forearm during spinal fMRI. Testing was always performed in the area outside of capsaicin application (i.e. area of secondary mechanical hyperalgesia). During slightly noxious mechanical stimulation before sensitization, activity was observed in ipsilateral dorsolateral pontine tegmentum (DLPT) which correlated with activity in ipsilateral spinal cord dorsal gray matter (dGM) suggesting activation of descending nociceptive inhibition. During secondary mechanical hyperalgesia, decreased activity was observed in bilateral DLPT, ipsilateral/midline rostral ventromedial medulla (RVM), and contralateral subnucleus reticularis dorsalis, which correlated with activity in ipsilateral dGM. Comparison of voxel-based activation patterns during mechanical stimulation before/after sensitization showed deactivations in RVM and activations in superficial ipsilateral dGM. This study revealed increased spinal activity and decreased activity in supraspinal centers involved in pain modulation (SRD, RVM, DLPT) during secondary mechanical hyperalgesia suggesting facilitation of nociception via decreased endogenous inhibition. Results should help prioritize approaches for further in vivo studies on pain processing and modulation in humans.
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Competing Interests: Ralf Baron reported grant/research support by: Pfizer, Genzyme, Grünenthal. Member of the IMI „Europain“ collaboration and industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly and Boehringer Ingelheim. German Federal Ministry of Education and Research (BMBF): German Research Network on Neuropathic Pain, Modelling Pain Switches. German Research Foundation (DFG). He received honoraria as a speaker from Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic, Eisai, UCB BioSciences, Lilly, Boehringer Ingelheim, Astellas, Desitin and as a consultant from Pfizer, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, UCB BioSciences, Lilly, Boehringer Ingelheim, Astellas, Novartis, Bristol-Myers Squibb, Biogenidec, AstraZeneca. Olav Jansen received honoraria as a speaker from Penumbra and as a consultant from Strykker, Philips and Boehringer Ingelheim. Janne Gierthmühlen received honoraria as a speaker from Pfizer and travel grants from Grünenthal. There are no conflicts of interests relevant to this article and none of the competing interests alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: JG. Performed the experiments: TR SW. Analyzed the data: TR PWS JG. Contributed reagents/materials/analysis tools: PWS. Contributed to the writing of the manuscript: TR CR RB PWS OJ JG.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0112325