• 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, Manuela De Gregori, Jacques E Chelly, Barbara A Rakel, Eske K Aasvang, Henrik Kehlet, BuhreWolfgang F F AWFFADepartment of Anesthesiology, Division of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Camron D Bryant, M Imad Damaj, Irah L King, Nader Ghasemlou, Jeffrey S Mogil, JoostenElbert A JEAJDepartment of Anesthesiology and Pain Management, Maastricht University Medical Center+, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, University of Maastricht, Maastricht, The Nether, and Luda Diatchenko.
• Faculty of Dental Medicine and Oral Health Sciences, Department of Anesthesia, Faculty of Medicine, Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
• Br J Anaesth. 2024 Aug 1; 133 (2): 360370360-370.

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.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

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