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Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia.
Nascimento de Lima, Ana Paula; Zhang, Huiran; Chen, Lubin; Effraim, Philip R; Gomis-Perez, Carolina; Cheng, Xiaoyang; Huang, Jianying; Waxman, Stephen G; Dib-Hajj, Sulayman D.
Afiliación
  • Nascimento de Lima AP; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Zhang H; Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Chen L; Center for Rehabilitation Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
  • Effraim PR; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Gomis-Perez C; Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Cheng X; Center for Rehabilitation Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
  • Huang J; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Waxman SG; Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Dib-Hajj SD; Center for Rehabilitation Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
Brain ; 147(9): 3157-3170, 2024 Sep 03.
Article en En | MEDLINE | ID: mdl-38447953
ABSTRACT
Vincristine-induced peripheral neuropathy is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine-induced pain. Our previous studies have shown that the tetrodotoxin-sensitive voltage-gated sodium channel Nav1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes to the maintenance of vincristine-induced allodynia. In this study, we investigated the effects of vincristine administration on excitability in small-diameter DRG neurons and whether the tetrodotoxin-resistant (TTX-R) Nav1.8 channels contribute to mechanical allodynia. Current-clamp recordings demonstrated that small DRG neurons become hyper-excitable following vincristine treatment, with both reduced current threshold and increased firing frequency. Using voltage-clamp recordings in small DRG neurons, we now show an increase in TTX-R current density and a -7.3 mV hyperpolarizing shift in the half-maximal potential (V1/2) of activation of Nav1.8 channels in vincristine-treated animals, which likely contributes to the hyperexcitability that we observed in these neurons. Notably, vincristine treatment did not enhance excitability of small DRG neurons from Nav1.8 knockout mice, and the development of mechanical allodynia was delayed but not abrogated in these mice. Together, our data suggest that sodium channel Nav1.8 in small DRG neurons contributes to the development of vincristine-induced mechanical allodynia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vincristina / Canal de Sodio Activado por Voltaje NAV1.8 / Ganglios Espinales / Hiperalgesia / Neuronas Límite: Animals Idioma: En Revista: Brain Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vincristina / Canal de Sodio Activado por Voltaje NAV1.8 / Ganglios Espinales / Hiperalgesia / Neuronas Límite: Animals Idioma: En Revista: Brain Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido