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Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain

Endogenous inflammatory mediators contribute to the pathogenesis of pain by acting on nociceptors, specialized sensory neurons that detect noxious stimuli. Here, we describe a new factor mediating inflammatory pain. We show that platelet-derived growth factor (PDGF)-BB applied in vitro causes repeti...

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Autores principales: Barkai, Omer, Puig, Stephanie, Lev, Shaya, Title, Ben, Katz, Ben, Eli-Berchoer, Luba, Gutstein, Howard B., Binshtok, Alexander M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553959/
https://www.ncbi.nlm.nih.gov/pubmed/30933959
http://dx.doi.org/10.1097/j.pain.0000000000001523
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author Barkai, Omer
Puig, Stephanie
Lev, Shaya
Title, Ben
Katz, Ben
Eli-Berchoer, Luba
Gutstein, Howard B.
Binshtok, Alexander M.
author_facet Barkai, Omer
Puig, Stephanie
Lev, Shaya
Title, Ben
Katz, Ben
Eli-Berchoer, Luba
Gutstein, Howard B.
Binshtok, Alexander M.
author_sort Barkai, Omer
collection PubMed
description Endogenous inflammatory mediators contribute to the pathogenesis of pain by acting on nociceptors, specialized sensory neurons that detect noxious stimuli. Here, we describe a new factor mediating inflammatory pain. We show that platelet-derived growth factor (PDGF)-BB applied in vitro causes repetitive firing of dissociated nociceptor-like rat dorsal root ganglion neurons and decreased their threshold for action potential generation. Injection of PDGF-BB into the paw produced nocifensive behavior in rats and led to thermal and mechanical pain hypersensitivity. We further detailed the biophysical mechanisms of these PDGF-BB effects and show that PDGF receptor–induced inhibition of nociceptive M-current underlies PDGF-BB–mediated nociceptive hyperexcitability. Moreover, in vivo sequestration of PDGF or inhibition of the PDGF receptor attenuates acute formalin-induced inflammatory pain. Our discovery of a new pain-facilitating proinflammatory mediator, which by inhibiting M-current activates nociceptive neurons and thus contributes to inflammatory pain, improves our understanding of inflammatory pain pathophysiology and may have important clinical implications for pain treatment.
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spelling pubmed-65539592019-07-22 Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain Barkai, Omer Puig, Stephanie Lev, Shaya Title, Ben Katz, Ben Eli-Berchoer, Luba Gutstein, Howard B. Binshtok, Alexander M. Pain Research Paper Endogenous inflammatory mediators contribute to the pathogenesis of pain by acting on nociceptors, specialized sensory neurons that detect noxious stimuli. Here, we describe a new factor mediating inflammatory pain. We show that platelet-derived growth factor (PDGF)-BB applied in vitro causes repetitive firing of dissociated nociceptor-like rat dorsal root ganglion neurons and decreased their threshold for action potential generation. Injection of PDGF-BB into the paw produced nocifensive behavior in rats and led to thermal and mechanical pain hypersensitivity. We further detailed the biophysical mechanisms of these PDGF-BB effects and show that PDGF receptor–induced inhibition of nociceptive M-current underlies PDGF-BB–mediated nociceptive hyperexcitability. Moreover, in vivo sequestration of PDGF or inhibition of the PDGF receptor attenuates acute formalin-induced inflammatory pain. Our discovery of a new pain-facilitating proinflammatory mediator, which by inhibiting M-current activates nociceptive neurons and thus contributes to inflammatory pain, improves our understanding of inflammatory pain pathophysiology and may have important clinical implications for pain treatment. Wolters Kluwer 2019-06 2019-02-18 /pmc/articles/PMC6553959/ /pubmed/30933959 http://dx.doi.org/10.1097/j.pain.0000000000001523 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Research Paper
Barkai, Omer
Puig, Stephanie
Lev, Shaya
Title, Ben
Katz, Ben
Eli-Berchoer, Luba
Gutstein, Howard B.
Binshtok, Alexander M.
Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
title Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
title_full Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
title_fullStr Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
title_full_unstemmed Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
title_short Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
title_sort platelet-derived growth factor activates nociceptive neurons by inhibiting m-current and contributes to inflammatory pain
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553959/
https://www.ncbi.nlm.nih.gov/pubmed/30933959
http://dx.doi.org/10.1097/j.pain.0000000000001523
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