{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T16:35:42Z","timestamp":1780677342511,"version":"3.54.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"crossref","award":["R21 DA020108"],"award-info":[{"award-number":["R21 DA020108"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R34NS126032"],"award-info":[{"award-number":["R34NS126032"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["PR9"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Introduction:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objectives:<\/jats:title>\n            <jats:p>Identify differentially methylated genes and pathways in symptomatic vs asymptomatic IVDs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Three lumbar IVDs with similar degeneration severity were tested prior to surgery by discography to identify symptomatic IVDs. Methylation analysis was performed on \u223c935,000 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/pr9.0000000000001237","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T13:09:10Z","timestamp":1740402550000},"page":"e1237","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the epigenetic landscape of symptomatic disk degeneration: a case 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