Evidence map›Paper›PMID 38862382›Full record

SynthesisBritish journal of anaesthesia2024

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 and 13 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in British journal of anaesthesia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Observational
  5. Observational
  6. Review
  7. Mechanism-based nonopioid analgesic targets.The Journal of clinical investigation · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Marc ParisienFaculty 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.
Roel R I van ReijDepartment 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 Netherlands.
Samar KhouryFaculty 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.
Eda KoseliDepartment of Pharmacology and Toxicology and Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Richmond, VA, USA.
Mohamad KarakyFaculty 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.
Jaqueline R SilvaDepartment of Anesthesiology, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada; Department of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada; Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
Golnar TaheriDepartment of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada; Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
Nynke J van den HoogenDepartment 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 Netherlands.
Garrie PengDepartment of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Massimo AllegriDepartment of Pain Therapy, Ensemble Hospitalier de la Côte, Morges, Switzerland.
Manuela De GregoriPain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Jacques E ChellyDepartment of Anesthesiology and Perioperative Medicine, University of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Barbara A RakelCollege of Nursing, University of Iowa, Iowa City, IA, USA.
Eske K AasvangDepartment of Anesthesiology, Centre for Cancer and Organ Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Henrik KehletSection of Surgical Pathophysiology 7621, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Wolfgang F F A BuhreDepartment of Anesthesiology, Division of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Camron D BryantCenter for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.
M Imad DamajDepartment of Pharmacology and Toxicology and Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Richmond, VA, USA.
Irah L KingDepartment of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; McGill Interdisciplinary Initiative in Infection and Immunity, McGill Centre for Microbiome Research, Montreal, QC, Canada.
Nader GhasemlouDepartment of Anesthesiology, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada; Department of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada; Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
Jeffrey S MogilDepartment of Psychology, Faculty of Science, Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
Elbert A J JoostenDepartment 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 Netherlands.
Luda DiatchenkoFaculty 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. Electronic address: luda.diatchenko@mcgill.ca.

Funding

Project-004U54DA049110 · NIDA · JOHNS HOPKINS UNIVERSITY · PI Martin Lindquist, TOR D. WAGER · 2019 to 2026
$14.7M
VCU Center for Drug Addiction ResearchP30DA033934 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI JOLENE J WINDLE · 2014 to 2026
$13.8M
A Reduced Complexity Cross in BALB/c substrains to identify the genetic basis of oxycodone dependence phenotypesU01DA050243 · NIDA · NORTHEASTERN UNIVERSITY · PI BRYANT, CAMRON D · 2020 to 2023
$3.3M
Systems genetics of premorbid and cocaine use traits in a rat reduced complexity crossU01DA055299 · NIDA · NORTHEASTERN UNIVERSITY · PI BRYANT, CAMRON D, KANTAK, KATHLEEN M. · 2022 to 2025
$2.8M
Genetic basis of chemotherapy-induced neuropathy in a reduced complexity crossR01CA221260 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI BRYANT, CAMRON D, DAMAJ, M. IMAD · 2018 to 2021
$1.7M
CIHRNCI NIH HHS R01 CA221260NIDA NIH HHS P30 DA033934NIDA NIH HHS U01 DA050243NIDA NIH HHS U01 DA055299NIDA NIH HHS U54 DA049110
6 · The paper itself

Abstract

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.

Indexed as

B-LymphocytesChronic PainGenome-Wide Association StudyPostoperative PainAnimalsDisease Models, AnimalFemaleHumansHyperalgesiaMaleMiceMice, KnockoutPolymorphism, Single NucleotideB cellschronic post-surgical paingenome-wide association studyimmune systemlymphocytes

Identifiers

PMID38862382
PMCPMC11282472

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.