Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.

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