Integrative Multiomic Analyses of Dorsal Root Ganglia in Diabetic Neuropathic Pain Using Proteomics, Phospho-proteomics, and Metabolomics

Overview

Journal Sci Rep

Specialty Science

Date 2022 Oct 11

PMID 36220867

Authors

Megan Doty

Sijung Yun

Yan Wang

Minghan Hu

Margaret Cassidy

Bradford Hall

Ashok B Kulkarni

Affiliations

Soon will be listed here.

Abstract

Diabetic peripheral neuropathy (DPN) is characterized by spontaneous pain in the extremities. Incidence of DPN continues to rise with the global diabetes epidemic. However, there remains a lack of safe, effective analgesics to control this chronic painful condition. Dorsal root ganglia (DRG) contain soma of sensory neurons and modulate sensory signal transduction into the central nervous system. In this study, we aimed to gain a deeper understanding of changes in molecular pathways in the DRG of DPN patients with chronic pain. We recently reported transcriptomic changes in the DRG with DPN. Here, we expand upon those results with integrated metabolomic, proteomic, and phospho-proteomic analyses to compare the molecular profiles of DRG from DPN donors and DRG from control donors without diabetes or chronic pain. Our analyses identified decreases of select amino acids and phospholipid metabolites in the DRG from DPN donors, which are important for cellular maintenance. Additionally, our analyses revealed changes suggestive of extracellular matrix (ECM) remodeling and altered mRNA processing. These results reveal new insights into changes in the molecular profiles associated with DPN.

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