ArticlePain2019
DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled 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.
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.
Who cites it
21 citing papers in PubMed, 3 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Transient Receptor Potential Ankyrin 1 (TRPA1) Methylation and Chronic Pain: A Systematic Review.Genes · 2023Pooled it
- Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition.Pain medicine (Malden, Mass.) · 2022Guideline
- Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review.Frontiers in endocrinology · 2021Pooled it
- Clostridium dalinum: A Novel Lactic Acid Bacterium with Excellent Antioxidant and Anti-inflammatory Functions Through NF-κB, Keap1-Nrf2-ARE Signaling Pathways.Probiotics and antimicrobial proteins · 2026Article
- Epigenetic, chromatin-associated, and epitranscriptomic regulation in chronic pain: mechanisms and translational prospects.Frontiers in genetics · 2026Review
- Optimising clinical trial methods for complex regional pain syndrome: a methodological framework (OptiMeth-CRPS).Pain reports · 2025Article
- Metabolomic Analysis of Sea Cucumber Ovum Hydrolysates in Cyclophosphamide-Induced Premature Ovarian Failure.Foods (Basel, Switzerland) · 2025Article
- [Biomarkers in complex regional pain syndrome].Schmerz (Berlin, Germany) · 2025Review
- An Integrative Review of Potential Diagnostic Biomarkers for Complex Regional Pain Syndrome.Journal of clinical medicine · 2025Review
- Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.International journal of molecular sciences · 2024Review
- CpG Methylation Levels in HPA Axis Genes Predict Chronic Pain Outcomes Following Trauma Exposure.The journal of pain · 2023Article
- Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.The journal of pain · 2022Observational
- Review
- Migraine and peripheral pain models show differential alterations in neuronal complexity.Headache · 2022Article
- Complex Regional Pain Syndrome: A Comprehensive Review.Pain and therapy · 2021Review
- Denying the Truth Does Not Change the Facts: A Systematic Analysis of Pseudoscientific Denial of Complex Regional Pain Syndrome.Journal of pain research · 2021Review
- A Role for Global DNA Methylation Level andFrontiers in pain research (Lausanne, Switzerland) · 2021Article
- Altered BDNF Methylation in Patients with Chronic Musculoskeletal Pain and High Biopsychosocial Complexity.Journal of pain research · 2020Article
- DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1.Pain research & management · 2020Article
- Next-generation DNA methylation sequencing: loci and regions differentially methylated in adolescents with chronic postsurgical pain.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Factors contributing to development of complex regional pain syndrome (CRPS) are not fully understood. This study examined possible epigenetic mechanisms that may contribute to CRPS after traumatic injury. DNA methylation profiles were compared between individuals developing CRPS (n = 9) and those developing non-CRPS neuropathic pain (n = 38) after undergoing amputation following military trauma. Linear Models for Microarray (LIMMA) analyses revealed 48 differentially methylated cytosine-phosphate-guanine dinucleotide (CpG) sites between groups (unadjusted P's < 0.005), with the top gene COL11A1 meeting Bonferroni-adjusted P < 0.05. The second largest differential methylation was observed for the HLA-DRB6 gene, an immune-related gene linked previously to CRPS in a small gene expression study. For all but 7 of the significant CpG sites, the CRPS group was hypomethylated. Numerous functional Gene Ontology-Biological Process categories were significantly enriched (false discovery rate-adjusted q value <0.15), including multiple immune-related categories (eg, activation of immune response, immune system development, regulation of immune system processes, and antigen processing and presentation). Differentially methylated genes were more highly connected in human protein-protein networks than expected by chance (P < 0.05), supporting the biological relevance of the findings. Results were validated in an independent sample linking a DNA biobank with electronic health records (n = 126 CRPS phenotype, n = 19,768 non-CRPS chronic pain phenotype). Analyses using PrediXcan methodology indicated differences in the genetically determined component of gene expression in 7 of 48 genes identified in methylation analyses (P's < 0.02). Results suggest that immune- and inflammatory-related factors might confer risk of developing CRPS after traumatic injury. Validation findings demonstrate the potential of using electronic health records linked to DNA for genomic studies of CRPS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.