Changes of sodium channel expression in experimental painful diabetic neuropathy

Authors

  • Matthew J. Craner MB, ChB, MRCP,

    1. Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT
    2. Rehabilitation Research Center, VA Connecticut Healthcare, West Haven, CT
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  • Joshua P. Klein BA,

    1. Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT
    2. Rehabilitation Research Center, VA Connecticut Healthcare, West Haven, CT
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  • Muthukrishnan Renganathan PhD,

    1. Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT
    2. Rehabilitation Research Center, VA Connecticut Healthcare, West Haven, CT
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  • Joel A. Black PhD,

    1. Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT
    2. Rehabilitation Research Center, VA Connecticut Healthcare, West Haven, CT
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  • Stephen G. Waxman MD, PhD

    Corresponding author
    1. Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT
    2. Rehabilitation Research Center, VA Connecticut Healthcare, West Haven, CT
    • Department of Neurology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510
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Abstract

Although pain is experienced by many patients with diabetic neuropathy, the pathophysiology of painful diabetic neuropathy is not understood. Substantial evidence indicates that dysregulated sodium channel gene transcription contributes to hyperexcitability of dorsal root ganglion neurons, which may produce neuropathic pain after axonal transection. In this study, we examined sodium channel mRNA and protein expression in dorsal root ganglion neurons in rats with streptozotocin-induced diabetes and tactile allodynia, using in situ hybridization and immunocytochemistry for sodium channels Nav1.1, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9. Our results show that, in rats with experimental diabetes, there is a significant upregulation of mRNA for the Nav1.3, Nav1.6, and Nav1.9 sodium channels and a downregulation of Nav1.8 mRNA 1 and 8 weeks after onset of allodynia. Channel protein levels display parallel changes. Our results demonstrate dysregulated expression of the genes for sodium channels Nav1.3, Nav1.6, Nav1.8, and Nav1.9 in dorsal root ganglion neurons in experimental diabetes and suggest that misexpression of sodium channels contributes to neuropathic pain associated with diabetic neuropathy.

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