ArticleThe journal of pain2023
CpG Methylation Levels in HPA Axis Genes Predict Chronic Pain Outcomes Following Trauma Exposure.
Article in The journal of pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Sex-specific molecular signatures in persistent pain after whiplash injury: an exploratory analysis.Pain reports · 2026Article
- Methylome-Wide Association Studies of Physical Injury Stratified by Depression Status Assesses Exposure by Diagnosis Effects in Oxytocin Signaling and Synaptic Plasticity.Biological psychiatry global open science · 2026Article
- Overweight and POMC methylation: epigenetic associations with adolescent depression.BMC psychiatry · 2025Article
- Examining the epigenetic transmission of risk for chronic pain associated with paternal post-traumatic stress disorder: a focus on veteran populations.Translational psychiatry · 2025Review
- Chronic pain as an emergent property of a complex system and the potential roles of psychedelic therapies.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum.Journal of clinical medicine · 2023Article
- Review
- The pace of biological aging significantly mediates the relationship between internalized stigma of chronic pain and chronic low back pain severity among non-hispanic black but not non-hispanic white adults.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 1 country.
Funding
Abstract
Chronic post-traumatic musculoskeletal pain (CPTP) is a common outcome of traumatic stress exposure. Biological factors that influence the development of CPTP are poorly understood, though current evidence indicates that the hypothalamic-pituitary-adrenal (HPA) axis plays a critical role in its development. Little is known about molecular mechanisms underlying this association, including epigenetic mechanisms. Here, we assessed whether peritraumatic DNA methylation levels at 248 5'-C-phosphate-G-3' (CpG) sites in HPA axis genes (FKBP5, NR3C1, CRH, CRHR1, CRHR2, CRHBP, POMC) predict CPTP and whether identified CPTP-associated methylation levels influence expression of those genes. Using participant samples and data collected from trauma survivors enrolled into longitudinal cohort studies (n = 290), we used linear mixed modeling to assess the relationship between peritraumatic blood-based CpG methylation levels and CPTP. A total of 66 (27%) of the 248 CpG sites assessed in these models statistically significantly predicted CPTP, with the three most significantly associated CpG sites originating from the POMC gene region (ie, cg22900229 [β = .124, P < .001], cg16302441 [β = .443, P < .001], cg01926269 [β = .130, P < .001]). Among the genes analyzed, both POMC (z = 2.36, P = .018) and CRHBP (z = 4.89, P < .001) were enriched in CpG sites significantly associated with CPTP. Further, POMC expression was inversely correlated with methylation levels in a CPTP-dependent manner (6-months NRS<4: r = -.59, P < .001; 6-months NRS ≥ 4: r = -.18, P = .2312). Our results suggest that methylation of HPA axis genes including POMC and CRHBP predict risk for and may contribute to vulnerability to CPTP. PERSPECTIVE: Peritraumatic blood levels of CpG methylation sites in HPA axis genes, particularly CpG sites in the POMC gene, predict CPTP development. This data substantially advances our understanding of epigenetic predictors and potential mediators of CPTP, a highly common, morbid, and hard-to-treat form of chronic pain.
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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.