Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy

Autor: Claire Gaveriaux-Ruff, Rohini Kuner, Peter P. Nawroth, Christoph S. N. Klose, Thomas Fleming, Nitin Agarwal, Anke Tappe-Theodor, Divija Deshpande
Přispěvatelé: univOAK, Archive ouverte, Heidelberg University Hospital [Heidelberg], Heidelberg University, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Supérieure de Biotechnologie de Strasbourg (ESBS), Université de Strasbourg (UNISTRA), Helmholtz Zentrum München = German Research Center for Environmental Health
Rok vydání: 2021
Předmět:
0301 basic medicine
Cell biology
endocrine system
medicine.medical_specialty
Molecular biology
Science
General Physics and Astronomy
Diseases
[SDV.GEN] Life Sciences [q-bio]/Genetics
Article
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Endocrinology
0302 clinical medicine
Proopiomelanocortin
Internal medicine
Diabetes mellitus
medicine
Endogenous opioid
[SDV.GEN]Life Sciences [q-bio]/Genetics
Multidisciplinary
biology
business.industry
digestive
oral
and skin physiology
General Chemistry
medicine.disease
Pro-Opiomelanocortin Deficiency
030104 developmental biology
medicine.anatomical_structure
Nociception
nervous system
Opioid
Peripheral nervous system
Neuropathic pain
biology.protein
business
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Neuroscience
medicine.drug
Zdroj: Nature Communications
Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-020-20677-0⟩
Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021)
Nat. Commun. 12:426 (2021)
ISSN: 2041-1723
DOI: 10.1038/s41467-020-20677-0
Popis: 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.
Proopiomelanocortin is an anti-nociceptive peptide. Here the authors show in a mouse model of diabetes, that this peptide is downregulated, which may contribute to the neuropathic pain like behaviour in these models.
Databáze: OpenAIRE
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