Background: Chronic widespread pain (CWP) is a common and debilitating condition characterized by persistent pain across multiple body regions. Recent advances in protein-profiling techniques enable measurements of blood proteins at scale and research into drug repurposing.

Objectives: This study aimed to identify therapeutic targets associated with CWP.

Methods: We used proteome-wide Mendelian randomization (phenome-wide MR) and colocalization analyses to assess potential causal effects of plasma proteins related to CWP phenotypes. The CWP GWAS data included 435,971 participants (2,149 cases) from the UK Biobank; protein quantitative trait loci (pQTL) data was available for 54,219 participants. Cis-SNPs (p < 5 × 10 ⁻⁸ ) within 1 Mb of protein-coding genes, with LD clumping (r² < 0.001) and an F-statistic > 10 were used as instrumental variables for each corresponding protein. For those proteins with marginal significant associations (p < 0.05), colocalization analyses were used to test the impact of linkage disequilibrium (H4, a measure of the likelihood that the genetic variant influences both the protein and disease). Finally, we searched potential existing therapies for repurposing based on their action on target proteins.

Results: We identified 101 plasma proteins significantly associated with CWP, of which 8 showed strong evidence of colocalization. Among these, LONP1, CD22, FAP, and KHK were associated with an increased risk of CWP (OR ranging from 1.40 to 2.08 and H4 values > 0.583), while FXYD5, AMPD3, COMMD1, and ADAMTSL2 were associated with a decreased CWP risk (OR between 0.39 and 0.66, H4 values ranging from 0.569 to 0.993). Notably, CD22 and FAP are already targeted by existing drugs, indicating their potential for repurposing: inotuzumab, ozogamicin and moxetumomab pasudotox; and f19 131i and sibrotuzumab respectively.

Conclusion: We identified 8 potential protein targets for CWP, with CD22 and FAP already targeted by existing drugs. These findings provide insights into the molecular mechanisms underlying CWP, and suggest repurposing opportunities for drug development and clinical testing.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.