ArticleNeurogastroenterology and motility2020
Sex differences in the epigenetic regulation of chronic visceral pain following unpredictable early life stress.
Article in Neurogastroenterology and motility, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Visual analysis of research hotspots and trends of external therapies in traditional Chinese medicine for chronic pain.Frontiers in medicine · 2025Pooled it
- Article
- Early life stress and the pathogenesis of visceral hypersensitivity: mechanisms and implications for disorders of gut-brain interaction.Frontiers in cell and developmental biology · 2026Review
- Sex Differences in the Effects of Early Life Stressors in a Rat Model of Myofascial Low Back Pain.European journal of pain (London, England) · 2025Article
- Effects of unpredictable chronic mild stress of female rats before pregnancy on morphine-induced antinociceptive tolerance in offspring.The Korean journal of pain · 2025Article
- The gut-brain axis and pain signalling mechanisms in the gastrointestinal tract.Nature reviews. Gastroenterology & hepatology · 2025Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice.Molecular pain · 2024Article
- Review
- Article
- Stress-Induced Changes in the Endogenous Opioid System Cause Dysfunction of Pain and Emotion Regulation.International journal of molecular sciences · 2023Review
- New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics.Journal of gastroenterology · 2023Review
- Sex Differences in Opioid Response Linked toJournal of clinical medicine · 2023Article
- Persistent inflammatory pain is linked with anxiety-like behaviors, increased blood corticosterone, and reduced global DNA methylation in the rat amygdala.Molecular pain · 2022Article
- The Role of Epigenomic Regulatory Pathways in the Gut-Brain Axis and Visceral Hyperalgesia.Cellular and molecular neurobiology · 2022Review
- Contribution of Amygdala Histone Acetylation in Early Life Stress-Induced Visceral Hypersensitivity and Emotional Comorbidity.Frontiers in neuroscience · 2022Article
- Stress-induced visceral pain in female rats is associated with epigenetic remodeling in the central nucleus of the amygdala.Neurobiology of stress · 2021Article
- Differential Activation of Colonic Afferents and Dorsal Horn Neurons Underlie Stress-Induced and Comorbid Visceral Hypersensitivity in Female Rats.The journal of pain · 2021Article
- Upregulation of spinal ASIC1 by miR-485 mediates enterodynia in adult offspring rats with prenatal maternal stress.CNS neuroscience & therapeutics · 2021Article
- Abdominal and Pelvic Pain: Current Challenges and Future Opportunities.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe previously reported that early life stress (ELS) dysregulated glucocorticoid receptor (GR) and corticotrophin-releasing hormone (CRH) expression in the central nucleus of the amygdala (CeA). Epigenetic modifications serve as memories of adverse events that occurred during early life. Therefore, we hypothesized that epigenetic mechanisms alter GR and CRH expression in the CeA and underlie chronic visceral pain after ELS.
methodsNeonatal rats were exposed to unpredictable, predictable ELS, or odor only (no stress control) from postnatal days 8 to 12. In adulthood, visceral sensitivity was assessed or the CeA was isolated for Western blot or ChiP-qPCR to study histone modifications at the GR and CRH promoters. Female adult rats underwent stereotaxic implantation of indwelling cannulas for microinjections of garcinol (HAT inhibitor) into the CeA. After 7 days of microinjections, visceral sensitivity was assessed or the CeA was isolated for ChIP-qPCR assays.
resultsUnpredictable ELS increased visceral sensitivity in adult female rats, but not in male counterparts. ELS increased histone 3 lysine 9 (H3K9) acetylation in the CeA and H3K9 acetylation levels at the GR promoter in the CeA of adult female rats. After unpredictable ELS, H3K9 acetylation was increased and GR binding was decreased at the CRH promoter. Administration of garcinol in the CeA of adult females, that underwent unpredictable ELS, normalized H3K9 acetylation and restored GR binding at the CRH promoter.
conclusionDysregulated histone acetylation and GR binding at the CRH promoter in the CeA are an important mechanism for "memorizing" ELS events mediating visceral pain in adulthood.
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