RT Journal Article
SR Electronic
T1 Transcriptomic Analysis of Human Sensory Neurons in Painful Diabetic Neuropathy Reveals Inflammation and Neuronal Loss
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.23.453576
DO 10.1101/2021.07.23.453576
A1 Hall, Bradford E.
A1 Macdonald, Emma
A1 Cassidy, Margaret
A1 Yun, Sijung
A1 Sapio, Matthew R.
A1 Ray, Pradipta
A1 Doty, Megan
A1 Nara, Pranavi
A1 Burton, Michael D.
A1 Shiers, Stephanie
A1 Ray-Chaudhury, Abhik
A1 Mannes, Andrew J.
A1 Price, Theodore J.
A1 Iadarola, Michael J.
A1 Kulkarni, Ashok B.
YR 2021
UL http://biorxiv.org/content/early/2021/07/25/2021.07.23.453576.abstract
AB Pathological sensations caused by peripheral painful neuropathy occurring in Type 2 diabetes mellitus (T2DM) are often described as ‘sharp’ and ‘burning’ and are commonly spontaneous in origin. Proposed etiologies implicate dysfunction of nociceptive sensory neurons in dorsal root ganglia (DRG) induced by generation of reactive oxygen species, microvascular defects, and ongoing axonal degeneration and regeneration. To investigate the molecular mechanisms contributing to diabetic pain, DRGs were acquired postmortem from patients who had been experiencing painful diabetic peripheral neuropathy (DPN) and subjected to transcriptome analyses to identify genes contributing to pathological processes and neuropathic pain. DPN occurs in distal extremities resulting in the characteristic “glove and stocking” pattern. Accordingly, the L4 and L5 DRGs, which contain the perikarya of primary afferent neurons innervating the foot, were analyzed from five DPN patients and compared with seven controls. Transcriptom e analyses identified 844 differentially expressed genes. We observed increases in levels of inflammation-associated genes from macrophages in DPN patients that may contribute to increased pain hypersensitivity and, conversely, there were frequent decreases in neuronally-related genes. The elevated inflammatory gene profile and the accompanying downregulation of multiple neuronal genes provide new insights into intraganglionic pathology and mechanisms causing neuropathic pain in DPN patients with T2DM.Competing Interest StatementAll authors have declared that no conflict of interest exists. TJP and PR are co-founders of Doloromics, a company developing novel pain therapeutics. Doloromics played no role in this study.