# Transcriptome Analysis of Rheumatoid Arthritis Uncovers Genes Linked to Inflammation-Induced Pain

**Authors:** Bradford E. Hall, Khadijah Mazhar, Emma Macdonald, Margaret Cassidy, Megan Doty, Christian Judkins, Anita Terse, Stephanie Shiers, Saber Tadros, Sijung Yun, Michael D. Burton, Theodore J. Price, Ashok Kulkarni

PMC · DOI: 10.21203/rs.3.rs-4218885/v1 · Research Square · 2024-04-19

## TL;DR

This study identifies genes in sensory neurons linked to chronic pain in rheumatoid arthritis patients.

## Contribution

The study reveals novel gene expression patterns in dorsal root ganglia associated with inflammation-induced pain in RA.

## Key findings

- 128 differentially expressed genes were identified in RA patients compared to controls.
- Upregulated immunoglobulin and immunological genes suggest autoimmune activity in sensory neurons.
- Neurogenesis-related genes were elevated, potentially contributing to pain hypersensitivity.

## 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.

## Linked entities

- **Diseases:** rheumatoid arthritis (MONDO:0008383), RA (MONDO:0005272)

## Full-text entities

- **Diseases:** temporomandibular joint (TMJ) arthralgia (MESH:D013706), RA (MESH:D001172), Autoimmune diseases (MESH:D001327), Pain (MESH:D010146), Inflammation (MESH:D007249), inflammatory synovitis (MESH:D013585), chronic pain (MESH:D059350)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11071542/full.md

## References

73 references — full list in the complete paper: https://tomesphere.com/paper/PMC11071542/full.md

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Source: https://tomesphere.com/paper/PMC11071542