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Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain
Journal article   Open access   Peer reviewed

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain

Marc Parisien, Roel R.I van Reij, Samar Khoury, Eda Koseli, Mohamad Karaky, Jaqueline R Silva, Golnar Taheri, Nynke J van den Hoogen, Garrie Peng, Massimo Allegri, …
British journal of anaesthesia : BJA, Vol.133(2), pp.360-370
08/2024
DOI: 10.1016/j.bja.2024.04.053
PMCID: PMC11282472
PMID: 38862382
url
https://doi.org/10.1016/j.bja.2024.04.053View
Published (Version of record) Open Access

Abstract

Background: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. Methods: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. Results: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. Conclusions: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.
 Immune System Lymphocytes Anesthesiology and Pain Medicine B cells chronic post-surgical pain genome-wide association study

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