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Diabetic Sensory Neurons, Dorsal Root Ganglia, and Neuropathy

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Diabetic Neuropathy

Part of the book series: Contemporary Diabetes ((CDI))

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Abstract

Sensory neurons are critical targets in diabetes mellitus (DM). Diabetic polyneuropathy (DPN) can be considered a unique form of sensory predominant neurodegeneration that renders loss of distal axon terminals, especially those in the skin, with relative preservation of their cell body (perikarya). Patients experience loss of sensation (numbness), gait instability with falls, unrecognized injury of insensate limbs with skin ulceration, and neuropathic pain. Sensory neurons reside in paraspinal dorsal root (and trigeminal) ganglia (DRGs) possessing unique microvascular and barrier properties that lead to greater vulnerability from DM. The molecular responses of sensory neurons differ from those of axotomized peripheral neurons. In DM the changes emphasize downregulation of key structural proteins, shifts in ion channel expression, and attenuated growth proteins all indicative of chronic neurotoxic stress. Changes in several differentially expressed mRNAs and miRNAs of DRG neurons in DPN, such as CWC22 and mmu-Let-7i, may contribute to sensory dysfunction. Finally, molecular strategies emphasizing regenerative impacts, including topical approaches, have the capacity to reverse features of DPN including loss of skin innervation. These have included local insulin (intrathecal, intranasal, near nerve, intrahindpaw) given in doses that do not alter hyperglycemia, GLP-1 agonists, PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibition or knockdown, and muscarinic antagonists. Several additional and novel strategies are emerging that may influence axonal degeneration of distal sensory terminals or axon regeneration specifically. Despite a limited clinical trial track record over several decades, new mechanistic insights for translation in DPN offer hope for better trial results.

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Acknowledgments

The effort devoted to this chapter was supported by current operating grants from the Canadian Institutes of Health Research (FRN148675 and 168929). The authors acknowledge the experimental work cited here and contributions by colleagues and trainees in the Zochodne laboratory. Work described has been supported since 1989 by the Canadian Institutes of Health Research, Canadian Diabetes Association, the Alberta Heritage Foundation for Medical Research, Muscular Dystrophy Association of Canada, University of Alberta Hospital Foundation, Department of Medicine and Division of Neurology, University of Alberta, NIDDK Complications Consortium, and the Juvenile Diabetes Foundation.

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Authors and Affiliations

  1. Peripheral Nerve Research Laboratory, Division of Neurology, Department of Medicine and the Neurosciences and Mental Health Institute, University of Alberta, Edmonton, AB, Canada

    Aparna Areti & Douglas W. Zochodne

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  1. Aparna Areti
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  2. Douglas W. Zochodne
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Correspondence to Douglas W. Zochodne .

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Editors and Affiliations

  1. Royal Hallamshire Hospital, Sheffield Teaching Hospitals and the University of Sheffield Director of Diabetes Research, Sheffield, UK

    Solomon Tesfaye

  2. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Christopher H. Gibbons

  3. Weill Cornell Medicine, Cornell University, Doha, Qatar

    Rayaz Ahmed Malik

  4. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Aristidis Veves

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Areti, A., Zochodne, D.W. (2023). Diabetic Sensory Neurons, Dorsal Root Ganglia, and Neuropathy. In: Tesfaye, S., Gibbons, C.H., Malik, R.A., Veves, A. (eds) Diabetic Neuropathy. Contemporary Diabetes. Humana, Cham. https://doi.org/10.1007/978-3-031-15613-7_18

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