Evidence map›Paper›PMID 39995491›Full record

ArticlePain reports2025

Investigating the epigenetic landscape of symptomatic disk degeneration: a case study.

Taylor D Yeater, Yuya Kawarai, Seunghwan Lee, Kumar G Belani, David S Beebe, Dmitriy Sheyn, Manuel R Pinto, Laura S Stone

Abstract read
In one paragraph

Article in Pain reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

8 authors.

Taylor D YeaterDepartment of Anesthesiology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
Yuya KawaraiDepartment of Orthopedic Surgery, Chiba University, Chiba, Japan.
Seunghwan LeeDepartment of Anesthesiology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
Kumar G BelaniDepartment of Anesthesiology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
David S BeebeDepartment of Anesthesiology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
Dmitriy SheynOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Manuel R PintoTwin Cities Spine Center, Minneapolis, MN, USA.
Laura S StoneDepartment of Anesthesiology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.ORCID https://orcid.org/0000-0002-7015-2101

Funding

Stem cell-loaded microgels to treat discogenic low back painR34NS126032 · NINDS · CEDARS-SINAI MEDICAL CENTER · PI SHEYN, DMITRIY · 2021 to 2021
$1.7M
Studying the mechanism of discogenic low back pain induction.R01AR082041 · NIAMS · CEDARS-SINAI MEDICAL CENTER · PI SHEYN, DMITRIY · 2024 to 2025
$1.0M
Proteomic Studies of Human Chronic PainR21DA020108 · NIDA · UNIVERSITY OF MINNESOTA · PI KEHL, LOIS · 2006 to 2007
$390k
NIAMS NIH HHS R01 AR082041NIDA NIH HHS R21 DA020108NINDS NIH HHS R34 NS126032
6 · The paper itself

Abstract

Introduction: This study investigates the epigenetic landscape underlying painful intervertebral disk (IVD) degeneration in a single subject with a history of low back pain (LBP). Intervertebral disk degeneration is associated with LBP in some individuals; however, there is often a discrepancy between degeneration and pain. We hypothesize that DNA methylation, an epigenetic mechanism previously linked to discogenic LBP, is dysregulated in symptomatic vs asymptomatic IVDs. Objectives: Identify differentially methylated genes and pathways in symptomatic vs asymptomatic IVDs. Methods: Three lumbar IVDs with similar degeneration severity were tested prior to surgery by discography to identify symptomatic IVDs. Methylation analysis was performed on ∼935,000 cytosine guanine dinucleotide sites on nucleus pulposus DNA. We explored differential methylation and pathway enrichment on cytosine guanine dinucleotide sites located within the promoter regions of genes. Results: Two IVDs (L3/L4 and L4/L5) evoked pain ratings of 10/10 and 8/10, one IVD (L5/S1) scored 0/10. DNA methylation differed between symptomatic and asymptomatic IVDs. Several identified genes have roles in extracellular matrix remodeling. Other differentially methylated genes were related to immunomodulation and ion channel function. Finally, several long noncoding RNA genes were identified, encouraging further exploration into these regulatory molecules. Enriched pathways were associated with immune response, hormonal regulation, nervous system development, and musculoskeletal development and remodeling. Conclusion: This case study provides a promising list of candidate genes for therapeutic development for discogenic LBP and suggests a role for DNA methylation in the development of symptomatic vs asymptomatic IVD degeneration, calling for further research to validate and expand these findings.

Indexed as

Back painDiscographyDNA methylationIntervertebral disksSpine

Identifiers

PMID39995491
PMCPMC11850048

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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.