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

Citation:

O. Barkai, S. Puig, S. Lev, B. Title, B. Katz, L. Eli-Berchoer, H.B. Gutstein, and A.M. Binshtok. 2019. “Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain.” Pain, 160, 6, Pp. 1281-1296.

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. © 2019 International Association for the Study of Pain.

Notes:

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Last updated on 02/09/2021