Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain.
Pain
; 160(6): 1281-1296, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30933959
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Receptoras Sensoriais
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Nociceptores
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Fator de Crescimento Derivado de Plaquetas
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Inflamação
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article