title: Changes of voltage-gated sodium channels in sensory nerve regeneration and neuropathic pain models.
abstract: OBJECTIVE
  The present study was conducted to determine changes in the expression of voltage-gated sodium channels (VGSCs) α-subunits after nerve injury and their relation with development of neuropathic pain.
  
  
  METHODS
  We used the crush injury model of regeneration of the sciatic nerve (Crush) and the spared nerve injury (SNI) model of neuropathic pain in the rat. Measurements of thermal and mechanical pain thresholds were performed until 3 months after injury. Real-time PCR and immunohistochemistry of VGSC α-subunits were used to evaluate the mRNA and protein expression in the DRG.
  
  
  RESULTS
  Both nerve injuries induced similar alterations in the VGSCs expression at 7 dpi, with upregulation of Nav1.3, and downregulation of Nav1.7, Nav1.8 and Nav1.9. These changes persisted until 28 days, when hyperalgesia was still present in SNI but not in Crush rats. At 90 days, mRNA expression of all analyzed α-subunits returned to basal levels in the Crush group. However, SNI rats still showed altered expression of VGSCs, and neuropathic pain responses. Immunohistochemical staining revealed that Nav1.8 and Nav1.9 were widely expressed in IB4-positive neurons of the DRG, relevant in pain processing. The population of neurons coexpressing each α-subunit and IB4 was also affected by the injury, more markedly after the Crush.
  
  
  CONCLUSIONS
  Shifts in VGSCs expression occur in parallel to neuropathic pain behavior in rats early after injury, while at later times they appear to be more related to sensory nerve degeneration and regeneration processes.
authors.affiliation: Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Casals-Díaz
authors.affiliation: Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Caty
authors.initials: C
authors.lastname: Casas
authors.affiliation: Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
mesh_terms: D000818:Animals; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D020426:Sciatic Neuropathy / Q000150:complications / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D061566:Voltage-Gated Sodium Channels
keywords: Neuropathic pain; axonal regeneration; nerve injury; sodium channel; spared nerve injury