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Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy

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...

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Autores principales: Deshpande, Divija, Agarwal, Nitin, Fleming, Thomas, Gaveriaux-Ruff, Claire, Klose, Christoph S. N., Tappe-Theodor, Anke, Kuner, Rohini, Nawroth, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814083/
https://www.ncbi.nlm.nih.gov/pubmed/33462216
http://dx.doi.org/10.1038/s41467-020-20677-0
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author Deshpande, Divija
Agarwal, Nitin
Fleming, Thomas
Gaveriaux-Ruff, Claire
Klose, Christoph S. N.
Tappe-Theodor, Anke
Kuner, Rohini
Nawroth, Peter
author_facet Deshpande, Divija
Agarwal, Nitin
Fleming, Thomas
Gaveriaux-Ruff, Claire
Klose, Christoph S. N.
Tappe-Theodor, Anke
Kuner, Rohini
Nawroth, Peter
author_sort Deshpande, Divija
collection PubMed
description 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.
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spelling pubmed-78140832021-01-25 Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy Deshpande, Divija Agarwal, Nitin Fleming, Thomas Gaveriaux-Ruff, Claire Klose, Christoph S. N. Tappe-Theodor, Anke Kuner, Rohini Nawroth, Peter Nat Commun Article 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. Nature Publishing Group UK 2021-01-18 /pmc/articles/PMC7814083/ /pubmed/33462216 http://dx.doi.org/10.1038/s41467-020-20677-0 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Deshpande, Divija
Agarwal, Nitin
Fleming, Thomas
Gaveriaux-Ruff, Claire
Klose, Christoph S. N.
Tappe-Theodor, Anke
Kuner, Rohini
Nawroth, Peter
Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy
title Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy
title_full Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy
title_fullStr Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy
title_full_unstemmed Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy
title_short Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy
title_sort loss of pomc-mediated antinociception contributes to painful diabetic neuropathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814083/
https://www.ncbi.nlm.nih.gov/pubmed/33462216
http://dx.doi.org/10.1038/s41467-020-20677-0
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