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 painhypersensitivity. We further detailed the biophysical mechanisms of these PDGF-BB effects and show that PDGFreceptor-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-currentactivates nociceptive neurons and thus contributes to inflammatory pain, improves our understanding of inflammatory pain pathophysiology and may have important clinical implications for pain treatment.
Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
Authors: Barkai O, Piug S, Lev S, Title B, Katz B, Eli-Berchoer L, Gutstein H, Binshtok AM
Year of publication: 2019
Journal: Pain, in press
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