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Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy

Author

Listed:
  • Divija Deshpande

    (University Hospital of Heidelberg
    Heidelberg University, INF 366
    Charité -Universitätsmedizin Berlin)

  • Nitin Agarwal

    (Heidelberg University, INF 366)

  • Thomas Fleming

    (University Hospital of Heidelberg
    German Center for Diabetes Research (DZD))

  • Claire Gaveriaux-Ruff

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Translational Medicine and Neurogenetics
    Université de Strasbourg
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale)

  • Christoph S. N. Klose

    (Charité -Universitätsmedizin Berlin)

  • Anke Tappe-Theodor

    (Heidelberg University, INF 366)

  • Rohini Kuner

    (Heidelberg University, INF 366)

  • Peter Nawroth

    (University Hospital of Heidelberg
    German Center for Diabetes Research (DZD)
    Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Zentrum)

Abstract

Painful neuropathy is a frequent complication in diabetes. Proopiomelanocortin (POMC) is an endogenous opioid precursor peptide, which plays a protective role against pain. Here, we report dysfunctional POMC-mediated antinociception in sensory neurons in diabetes. In streptozotocin-induced diabetic mice the Pomc promoter is repressed due to increased binding of NF-kB p50 subunit, leading to a loss in basal POMC level in peripheral nerves. Decreased POMC levels are also observed in peripheral nervous system tissue from diabetic patients. The antinociceptive pathway mediated by POMC is further impaired due to lysosomal degradation of μ-opioid receptor (MOR). Importantly, the neuropathic phenotype of the diabetic mice is rescued upon viral overexpression of POMC and MOR in the sensory ganglia. This study identifies an antinociceptive mechanism in the sensory ganglia that paves a way for a potential therapy for diabetic neuropathic pain.

Suggested Citation

  • Divija Deshpande & Nitin Agarwal & Thomas Fleming & Claire Gaveriaux-Ruff & Christoph S. N. Klose & Anke Tappe-Theodor & Rohini Kuner & Peter Nawroth, 2021. "Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20677-0
    DOI: 10.1038/s41467-020-20677-0
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