Abstract| Volume 22, ISSUE 5, P581, May 2021

Mitochondrial Calcium Uniporter Deletion Prevents Painful Diabetic Neuropathy by Restoring Mitochondrial Morphology and Dynamics

      This paper is only available as a PDF. To read, Please Download here.
      Painful diabetic neuropathy (PDN) is an intractable complication affecting 25% of diabetic patients. PDN is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, resulting in calcium overload, axonal degeneration, and loss of cutaneous innervation. However, the underlying molecular pathways responsible for these effects are unknown. Using highly stringent quantitative proteomic analyses, we found that mitochondrial proteins are differentially expressed in DRG neurons from mice with PDN caused by a high fat diet (HFD). In particular, mitochondrial fission proteins were overexpressed. Electron microscopy demonstrated fragmented mitochondrial morphology in DRG nociceptors. In vivo calcium imaging revealed increased calcium signaling in Nav1.8-expressing DRG neurons of HFD mice. Selectively deleting the mitochondrial calcium uniporter from these neurons restored normal mitochondrial morphology and dynamics, prevented axonal degeneration, and reversed mechanical allodynia. Hence, we propose that targeting calcium entry into nociceptor mitochondria may be a promising therapeutic approach for PDN patients. Moreover, these results may illuminate other neurodegenerative diseases involving similar underlying events 5R01NS104295-02
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect