Loss of POMC-mediated Antinociception Contributes to Painful Diabetic Neuropathy

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 19

PMID 33462216

Citations 12

Authors

Divija Deshpande

Nitin Agarwal

Thomas Fleming

Claire Gaveriaux-Ruff

Christoph S N Klose

Anke Tappe-Theodor

Rohini Kuner

Peter Nawroth

Affiliations

Soon will be listed here.

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.

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