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Papers of the Week

Papers: 18 Mar 2023 - 24 Mar 2023


Genetics, Human Studies, Neurobiology

2023 Mar 10



Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain.


Parisien M, van Reij RRI, Khoury S, Koseli E, Karaky M, van den Hoogen NJ, Peng G, Allegri M, de Gregori M, Chelly JE, Rakel BA, Aasvang EK, Kehlet H, Buhre WFFA, Bryant CD, Damaj MI, King IL, Mogil JS, Joosten EAJ, Diatchenko L


Chronic post-surgical pain affects a large proportion of people undergoing surgery, delaying recovery time and worsening quality of life. Although many environmental variables have been established as risk factors, less is known about genetic risk. To uncover genetic risk factors we performed genome-wide association studies in post-surgical cohorts of five surgery types- hysterectomy, mastectomy, abdominal, hernia, and knee- totaling 1350 individuals. Genetic associations between post-surgical chronic pain levels on a numeric rating scale (NRS) and additive genetic effects at common SNPs were evaluated. We observed genome-wide significant hits in almost all cohorts that displayed significance at the SNP, gene, and pathway levels. The cohorts were then combined via a GWAS meta-analysis framework for further analyses. Using partitioned heritability, we found that loci at genes specifically expressed in the immune system carried enriched heritability, especially genes related to B and T cells. The relevance of B cells in particular was then demonstrated in mouse postoperative pain assays. Taken altogether, our results suggest a role for the adaptive immune system in chronic post-surgical pain.