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Nav1.7 is essential for nociceptor action potentials in the mouse in a manner independent of endogenous opioids.
Deng, Lunbin; Dourado, Michelle; Reese, Rebecca M; Huang, Kevin; Shields, Shannon D; Stark, Kimberly L; Maksymetz, James; Lin, Han; Kaminker, Joshua S; Jung, Min; Foreman, Oded; Tao, Janet; Ngu, Hai; Joseph, Victory; Roose-Girma, Meron; Tam, Lucinda; Lardell, Susanne; Orrhult, Linnea Strid; Karila, Paul; Allard, Julien; Hackos, David H.
Afiliación
  • Deng L; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Dourado M; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Reese RM; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Huang K; Department of OMNI Bioinformatics, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Shields SD; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Stark KL; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Maksymetz J; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Lin H; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Kaminker JS; Department of OMNI Bioinformatics, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Jung M; Department of OMNI Bioinformatics, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Foreman O; Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Tao J; Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Ngu H; Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Joseph V; Department of Biomedical Imaging, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
  • Roose-Girma M; Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
  • Tam L; Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
  • Lardell S; Cellectricon AB, Neongatan 4B, 431 53 Mölndal, Sweden.
  • Orrhult LS; Cellectricon AB, Neongatan 4B, 431 53 Mölndal, Sweden.
  • Karila P; Cellectricon AB, Neongatan 4B, 431 53 Mölndal, Sweden.
  • Allard J; E-Phys, CRBC, 28 place Henri Dunant, 63000 Clermont-Ferrand, France. Electronic address: julien.allard@e-phys.com.
  • Hackos DH; Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA. Electronic address: hackos.david@gene.com.
Neuron ; 111(17): 2642-2659.e13, 2023 09 06.
Article en En | MEDLINE | ID: mdl-37352856
Loss-of-function mutations in Nav1.7, a voltage-gated sodium channel, cause congenital insensitivity to pain (CIP) in humans, demonstrating that Nav1.7 is essential for the perception of pain. However, the mechanism by which loss of Nav1.7 results in insensitivity to pain is not entirely clear. It has been suggested that loss of Nav1.7 induces overexpression of enkephalin, an endogenous opioid receptor agonist, leading to opioid-dependent analgesia. Using behavioral pharmacology and single-cell RNA-seq analysis, we find that overexpression of enkephalin occurs only in cLTMR neurons, a subclass of sensory neurons involved in low-threshold touch detection, and that this overexpression does not play a role in the analgesia observed following genetic removal of Nav1.7. Furthermore, we demonstrate using laser speckle contrast imaging (LSCI) and in vivo electrophysiology that Nav1.7 function is required for the initiation of C-fiber action potentials (APs), which explains the observed insensitivity to pain following genetic removal or inhibition of Nav1.7.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nociceptores / Analgésicos Opioides Límite: Animals / Humans Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nociceptores / Analgésicos Opioides Límite: Animals / Humans Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos