Evidence map›Paper›PMID 34958702›Full record

SynthesisEuropean journal of pain (London, England)2022

Different genes may be involved in distal and local sensitization: A genome-wide gene-based association study and meta-analysis.

Afroditi Kouraki, Michael Doherty, Gwen S Fernandes, Weiya Zhang, David A Walsh, Anthony Kelly, Ana M Valdes

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European journal of pain (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 45% of its field
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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. 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

7 authors at 5 institutions in 1 country.

Afroditi KourakiAcademic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
Michael DohertyAcademic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
Gwen S FernandesPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Weiya ZhangAcademic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
David A WalshAcademic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
Anthony KellyAcademic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
Ana M ValdesAcademic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
Nottingham City Hospital · GBUniversity of Nottingham · GBNottingham Biomedical Research Centre · GBUniversity of Bristol · GBVersus Arthritis · GB

Funding

Department of HealthMedical Research Council MC_PC_19095Versus Arthritis
6 · The paper itself

Abstract

backgroundNeuropathic pain symptoms and signs of increased pain sensitization in osteoarthritis (OA) patients may explain persistent pain after total joint replacement (TJR). Therefore, identifying genetic markers associated with pain sensitization and neuropathic-like pain phenotypes could be clinically important in identifying targets for early intervention.

methodsWe performed a genome-wide gene-based association study (GWGAS) using pressure pain detection thresholds (PPTs) from distal pain-free sites (anterior tibia), a measure of distal sensitization, and from proximal pain-affected sites (lateral joint line), a measure of local sensitization, in 320 knee OA participants from the Knee Pain and related health in the Community (KPIC) cohort. We next performed gene-based fixed-effects meta-analysis of PPTs and a neuropathic-like pain phenotype using genome-wide association study (GWAS) data from KPIC and from an independent cohort of 613 post-TJR participants, respectively.

resultsThe most significant genes associated with distal and local sensitization were OR5B3 and BRDT, respectively. We also found previously identified neuropathic pain-associated genes-KCNA1, MTOR, ADORA1 and SCN3B-associated with PPT at the anterior tibia and an inflammatory pain gene-PTAFR-associated with PPT at the lateral joint line. Meta-analysis results of anterior tibia and neuropathic-like pain phenotypes revealed genes associated with bone morphogenesis, neuro-inflammation, obesity, type 2 diabetes, cardiovascular disease and cognitive function.

conclusionsOverall, our results suggest that different biological processes might be involved in distal and local sensitization, and common genetic mechanisms might be implicated in distal sensitization and neuropathic-like pain. Future studies are needed to replicate these findings. SIGNIFICANCE: To the best of our knowledge, this is the first GWAS for pain sensitization and the first gene-based meta-analysis of pain sensitization and neuropathic-like pain. Higher pain sensitization and neuropathic pain symptoms are associated with persistent pain after surgery hence, identifying genetic biomarkers and molecular pathways associated with these traits is clinically relevant.

Indexed as

Diabetes Mellitus, Type 2NeuralgiaOsteoarthritis, KneeGenome-Wide Association StudyHumansKnee JointPain Threshold

Identifiers

PMID34958702
PMCPMC9303629
OpenAlexW4200396461

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.