Abstract

Autoimmune diseases such as rheumatoid arthritis (RA) can promote states of chronic inflammation with accompanying tissue destruction and pain. RA can cause inflammatory synovitis in peripheral joints, particularly within the hands and feet, but can also sometimes trigger temporomandibular joint (TMJ) arthralgia. To better understand the effects of ongoing inflammation-induced pain signaling, dorsal root ganglia (DRGs) were acquired from individuals with RA for transcriptomic study. We conducted RNA sequencing from the L5 DRGs because it contains the soma of the sensory neurons that innervate the affected joints in the foot. DRGs from 5 RA patients were compared with 9 non-arthritic controls. RNA-seq of L5 DRGs identified 128 differentially expressed genes (DEGs) that were dysregulated in the RA subjects as compared to the non-arthritic controls. The DRG resides outside the blood brain barrier and, as such, our initial transcriptome analysis detected signs of an autoimmune disorder including the upregulated expression of immunoglobulins and other immunologically related genes within the DRGs of the RA donors. Additionally, we saw the upregulation in genes implicated in neurogenesis that could promote pain hypersensitivity. Overall, our DRG analysis suggests that there are upregulated inflammatory and pain signaling pathways that can contribute to chronic pain in RA.

Details

Title
Transcriptome analysis of rheumatoid arthritis uncovers genes linked to inflammation-induced pain
Author
Hall, Bradford E. 1 ; Mazhar, Khadijah 2 ; Macdonald, Emma 3 ; Cassidy, Margaret 4 ; Doty, Megan 5 ; Judkins, Christian 6 ; Terse, Anita 1 ; Shiers, Stephanie 2 ; Tadros, Saber 7 ; Yun, Sijung 8 ; Burton, Michael D. 9 ; Price, Theodore J. 2 ; Kulkarni, Ashok B. 1 

 National Institute of Dental and Craniofacial Research, National Institutes of Health, Functional Genomics Section, Bethesda, USA (GRID:grid.419633.a) (ISNI:0000 0001 2205 0568) 
 The University of Texas at Dallas, Department of Neuroscience and Center for Advanced Pain Studies, Dallas, USA (GRID:grid.267323.1) (ISNI:0000 0001 2151 7939) 
 National Institute of Dental and Craniofacial Research, National Institutes of Health, Functional Genomics Section, Bethesda, USA (GRID:grid.419633.a) (ISNI:0000 0001 2205 0568); Brown University, NIH Graduate Partnerships Program, Providence, USA (GRID:grid.40263.33) (ISNI:0000 0004 1936 9094) 
 National Institute of Dental and Craniofacial Research, National Institutes of Health, Functional Genomics Section, Bethesda, USA (GRID:grid.419633.a) (ISNI:0000 0001 2205 0568); U. Penn, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
 National Institute of Dental and Craniofacial Research, National Institutes of Health, Functional Genomics Section, Bethesda, USA (GRID:grid.419633.a) (ISNI:0000 0001 2205 0568); Dartmouth, Hanover, USA (GRID:grid.419633.a) 
 National Institute of Dental and Craniofacial Research, National Institutes of Health, Functional Genomics Section, Bethesda, USA (GRID:grid.419633.a) (ISNI:0000 0001 2205 0568); Millipore Sigma, Rockville, USA (GRID:grid.419633.a) 
 National Cancer Institute, National Institutes of Health, Laboratory of Pathology, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
 Predictiv Care, Inc, Mountain View, USA (GRID:grid.48336.3a) 
 University of Texas at Dallas, Neuroimmunology and Behavior Laboratory, Department of Neuroscience, Center for Advanced Pain Studies, School of Behavioral and Brain Sciences, Richardson, USA (GRID:grid.267323.1) (ISNI:0000 0001 2151 7939) 
Pages
25893
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3121801741
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.