Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain. Issue 6 (June 2019)

• Record Type: Journal Article
• Authors: Barkai, Omer; Puig, Stephanie; Lev, Shaya; Title, Ben; Katz, Ben; Eli-Berchoer, Luba; Gutstein, Howard B.; Binshtok, Alexander M.
• Is Part Of: Pain. Volume 160:Issue 6(2019)
• Publication Date: 2019-06
• Subjects: Inflammatory pain -- Nociceptor excitability -- Kv7 channels -- M-current -- PDGF; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001523
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is Available in the Text.Our work reveals that the platelet-derived growth factor-BB, by inhibiting nociceptive M-type potassium channels, acts as a pain-inducing proinflammatory factor that significantly contributes to inflammatory pain.