# Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain

## TL;DR

This study explores how a specific fatty acid, 17-HDHA, is linked to chronic pain through gene activity in monocytes, suggesting a biological pathway that could explain pain differences.

## Contribution

The study identifies eIF2 signaling as a novel biological pathway associated with 17-HDHA levels and chronic pain in osteoarthritis.

## Key findings

- 17-HDHA levels correlate with gene expression in classical monocytes.
- eIF2 signaling is the top pathway affected by 17-HDHA and pain levels.
- Other pathways like eIF4, P70S6K, and mTOR are also involved.

## Abstract

Our goal was to probe the potential transcriptomic basis for the relationship between plasma levels of the specialized pro-resolving precursor, 17-hydroxy-docosahexaenoic acid (17-HDHA) and chronic pain. Participants with osteoarthritis (average age of 62.3, 60% were female, n = 30) were stratified by levels of 17-HDHA and self-reported pain scores. RNAs from CD14++/CD16-/CD66b-/HLA-DR+ (classical) monocytes were sequenced and differentially expressed mRNAs were identified with DESeq2. QIAGEN ingenuity pathway analysis identified the top ranked canonical biological pathway to be eukaryotic initiation factor 2 (EIF2) signaling (lower activation level in the low 17-HDHA-high pain group compared to the high 17-HDHA-low pain group (Z score −3)), followed by EIF4 and P70S6K signaling pathways and mTOR signaling. Our approach provides insight into the biological pathways contributing to the association between 17-HDHA and chronic osteoarthritis (OA) pain, identifying EIF2 signaling, with known roles in osteoclast differentiation, OA pathology, and pain, as a potential downstream target.

•Expression levels of PLA2G6 and EPHX2 were associated with levels of 17-HDHA•eIF2 signaling was the top ranked pathway in classical monocytes between key groups•The next highly ranked pathways were eIF4, P70S6K, and mTOR signaling

Expression levels of PLA2G6 and EPHX2 were associated with levels of 17-HDHA

eIF2 signaling was the top ranked pathway in classical monocytes between key groups

The next highly ranked pathways were eIF4, P70S6K, and mTOR signaling

Biological sciences; Molecular neuroscience; Neuroscience