731: 17-HDHA–associated transcriptomic signatures distinguish osteoarthritis pain phenotypes

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, , , , , , Neuroimmunology, Omics (Proteomics/Metabolomics/Transcriptomics/Genomics), , ,

Background and Aims: Osteoarthritis (OA) is commonly associated with chronic pain that substantially affects daily life, although not all individuals with OA experience pain. Understanding these differences may reveal novel therapeutic targets. Specialised pro-resolving mediators (SPMs), including resolvins, are endogenous lipid molecules with potent analgesic properties. Resolvins are rapidly degraded in vivo, whereas their precursor, 17-hydroxydocosahexaenoic acid (17-HDHA) is more stable. We have previously shown that lower circulating 17-HDHA levels are associated with increased pain scores in people with OA. This study aimed to define the cellular and molecular mechanisms underlying 17-HDHA–mediated analgesia, with a focus on monocyte miRNA signalling.

Methods: Participants with chronic knee pain (n=100) and pain-free age and sex matched controls (n=30) were recruited from Nottingham’s Investigating Musculoskeletal Health and Wellbeing cohort. Blood was collected from participants and PBMCs were isolated. Classical, intermediate, and non-classical monocytes were isolated from PBMCs using Fluorescence-activated cell sorting. Plasma levels of 17-HDHA were quantified by LC-MS/MS.
Participants were stratified into groups based on levels of pain and 17-HDHA. RNA was isolated from the three populations of monocytes and analysed for mRNA and miRNA using next-generation sequencing. Differential gene expression analysis was performed between groups.

Results: Levels of 17-HDHA had a range of 0.04-1.9 nM across the cohort, with a median value of 0.38 nM. The NRS pain score had a range of 0-10 with a median of 5. These values were used as group cut offs, and were consistent with previous studies. DGE analysis identified mRNA and miRNA differentially expressed between the Low Pain-High 17-HDHA and High Pain-Low 17-HDHA groups. Identified miRNA included: miR-30b-5p; miR-24-3p; miR-17-5p; miR-149-5p; and miR-92a-3p. Key targets of these miRNAs, which were also differentially expressed included: IL-6 and CXCL10.

Conclusions: This study demonstrates that circulating 17-HDHA levels are associated with distinct monocyte mRNA and miRNA signatures that differentiate OA pain phenotypes, supporting a role for lipid–immune–miRNA crosstalk in endogenous analgesia. Differentially expressed miRNAs and their targets implicate pathways linked to redox balance, lipid metabolism, and cellular differentiation as potential mediators of pain resolution. Future studies will functionally validate these miRNAs in vitro and in vivo to assess mechanistic effects on nociceptive signalling.

References: -

Presenting Author: James Turnbull
Submitting Author: James Turnbull

Senior Author: Victoria Chapman

IASP 2026 Global Year theme of Neuropathic Pain: No

• Vasilius Georgopoulos - University of Nottingham
• Tony Kelly - University of Nottingham
• David Onion - University of Nottingham
• Alex Rathbone - University of Nottingham
• Sandeep Shankar Amberkar - Neuroscience Genetics, Eli Lilly and Company
• Emma Rousseau - Neuroscience Genetics, Eli Lilly and Company
• Gopuraja Dharmalingam - Neuroscience Genetics, Eli Lilly and Company
• Emanuele Sher - Neuroscience Genetics, Eli Lilly and Company
• Ana Valdes - University of Nottingham
• David Walsh - University of Nottingham
• Federico Dajas-Bailador - University of Nottingham
• Victoria Chapman - University of Nottingham