慢性疼痛
医学
遗传关联
全基因组关联研究
生活质量(医疗保健)
生物信息学
物理疗法
生物
单核苷酸多态性
遗传学
基因型
基因
护理部
作者
Marc Parisien,Roel R.I. van Reij,Samar Khoury,Eda Köşeli,Mohamad Karaky,Jaqueline Raymondi Silva,Golnar Taheri,Nynke J. van den Hoogen,Garrie Peng,Massimo Allegri,Manuela De Gregori,Jacques E. Chelly,Barbara A. Rakel,Eske Kvanner Aasvang,Henrik Kehlet,Wolfgang Buhre,Camron D. Bryant,M. Imad Damaj,Irah L. King,Nader Ghasemlou,Jeffrey S. Mogil,Elbert A. Joosten,Luda Diatchenko
标识
DOI:10.1016/j.bja.2024.04.053
摘要
BackgroundChronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood.MethodsA 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.ResultsWe 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.ConclusionsThese findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.
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