ArticlePediatric research2025
Repetitive neonatal pain increases spinal cord DNA methylation of the µ-opioid receptor.
Article in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Identification of a different DNA methylation pattern for pain related genes in children with intellectual disability: a cross-sectional study.Italian journal of pediatrics · 2026Article
- Epigenetic remodeling: unveiling the potential endogenous mechanisms of exercise in alleviating neuropathic pain.Frontiers in neuroscience · 2025Review
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Authors and funding
5 authors.
Funding
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Abstract
backgroundRepetitive neonatal painful procedures experienced in the neonatal intensive care unit (NICU) are known to alter the development of the nociceptive system and have long-lasting consequences. Recent evidence indicates that NICU stay affects the methylation of the opioid receptor mu 1 encoding gene (Mor-1). Additionally, a preclinical model of neonatal procedural pain established lower adult post-operative MOR-1 levels in the spinal cord. Thus, we hypothesized that neonatal procedural pain increases the DNA methylation status of Mor-1 in the spinal cord and dorsal root ganglia (DRGs).
methodsTo this end, repetitive neonatal procedural pain was induced in animals, during the first postnatal week, a period equivalent to preterm human brain development. On postnatal day 10 methylation of Mor-1 promotor was assessed in the spinal cord and the DRG using bisulfite pyrosequencing.
resultsOur findings demonstrated that neonatal procedural pain increased spinal cord Mor-1 promotor DNA methylation in the ipsilateral side as compared to the contralateral side, an effect that was not observed in the control animals, nor in the DRG.
conclusionThis study is the first to highlight a localized and noxious-stimuli-dependent effect of repetitive neonatal procedural pain on Mor-1 promotor methylation and emphasizes the need to explore the effects of repetitive neonatal procedural pain on the epigenome. IMPACT: This study reveals that repetitive neonatal procedural pain is associated with increased DNA methylation of the Mor-1 promoter in the spinal cord of neonatal rats. This is the first study to identify an effect of neonatal procedural pain on DNA methylation, emphasizing the critical need for further investigation into the epigenetic consequences of neonatal procedural pain. These insights could lead to better management and treatment strategies to mitigate the long-term impacts of early pain exposure on neurodevelopment and behavior.
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