Different genes may be involved in distal and local sensitization: A genome‐wide gene‐based association study and meta‐analysis

Abstract

Background Neuropathic pain symptoms and signs of increased pain sensitization in osteoarthritis (OA) patients may explain persistent pain after total joint replacement (TJR). Therefore, identifying genetic markers associated with pain sensitization and neuropathic‐like pain phenotypes could be clinically important in identifying targets for early intervention. 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.

Precision management of post‐COVID pain: An evidence and clinical‐based approach

“…Polymorphic alterations of candidate genes have been investigated for the role they may play in post‐COVID pain and viral aggressiveness. Among the different genes, the ACE2 and the TMPRSS2 polymorphisms are candidates for what concerns the effect of viral infection (Adli et al, 2022), whereas the more canonical genes previously associated with pain perception and some chronic pain conditions are the SNP of the μ‐opioid receptor gene (OPRM1), the Val158Met catechol‐O‐methyltransferase gene (COMT), the brain‐derived neurotrophic factor (BDNF) and the 5‐hydroxytryptamine receptor 1B gene (HTR1B) (Kouraki et al, 2022). Polymorphisms of pain process genes have been mostly associated with altered activity of protein products leading to pain features and alteration in pain signalling (Zorina‐Lichtenwalter et al, 2016).…”