Abstract | BACKGROUND: METHODS: We performed a genome-wide gene-based association study (GWGAS) using pressure pain detection thresholds (PPTs) from distal pain-free sites (anterior tibia), a measure of distal sensitization, and from proximal pain-affected sites (lateral joint line), a measure of local sensitization, in 320 knee OA participants from the Knee Pain and related health in the Community (KPIC) cohort. We next performed gene-based fixed-effects meta-analysis of PPTs and a neuropathic-like pain phenotype using genome-wide association study (GWAS) data from KPIC and from an independent cohort of 613 post-TJR participants, respectively. RESULTS: The most significant genes associated with distal and local sensitization were OR5B3 and BRDT, respectively. We also found previously identified neuropathic pain-associated genes-KCNA1, MTOR, ADORA1 and SCN3B-associated with PPT at the anterior tibia and an inflammatory pain gene-PTAFR-associated with PPT at the lateral joint line. Meta-analysis results of anterior tibia and neuropathic-like pain phenotypes revealed genes associated with bone morphogenesis, neuro- inflammation, obesity, type 2 diabetes, cardiovascular disease and cognitive function. CONCLUSIONS: Overall, our results suggest that different biological processes might be involved in distal and local sensitization, and common genetic mechanisms might be implicated in distal sensitization and neuropathic-like pain. Future studies are needed to replicate these findings. SIGNIFICANCE: To the best of our knowledge, this is the first GWAS for pain sensitization and the first gene-based meta-analysis of pain sensitization and neuropathic-like pain. Higher pain sensitization and neuropathic pain symptoms are associated with persistent pain after surgery hence, identifying genetic biomarkers and molecular pathways associated with these traits is clinically relevant.
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Authors | Afroditi Kouraki, Michael Doherty, Gwen S Fernandes, Weiya Zhang, David A Walsh, Anthony Kelly, Ana M Valdes |
Journal | European journal of pain (London, England)
(Eur J Pain)
Vol. 26
Issue 3
Pg. 740-753
(03 2022)
ISSN: 1532-2149 [Electronic] England |
PMID | 34958702
(Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®. |
Topics |
- Diabetes Mellitus, Type 2
(complications)
- Genome-Wide Association Study
- Humans
- Knee Joint
- Neuralgia
- Osteoarthritis, Knee
- Pain Threshold
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