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

Omer Barkai, Stephanie Puig, Shaya Lev, Ben Title, Ben Katz, Luba Eli-Berchoer, Howard B. Gutstein, Alexander M. Binshtok*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1281-1296
Number of pages16
JournalPain
Volume160
Issue number6
DOIs
StatePublished - 1 Jun 2019

Bibliographical note

Publisher Copyright:
© 2019 International Association for the Study of Pain.

Keywords

  • Inflammatory pain
  • Kv7 channels
  • M-current
  • Nociceptor excitability
  • PDGF

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