ArticleMolecular pain2022
Persistent inflammatory pain is linked with anxiety-like behaviors, increased blood corticosterone, and reduced global DNA methylation in the rat amygdala.
Article in Molecular pain, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The impact of psychological interventions on anxiety and depression in cancer pain patients: A meta-analysis.Medicine · 2026Pooled it
- A Dnmt3a-Mediated Epigenetic Mechanism for Chronic-Pain-Induced Behaviors of Negative Emotion in Mice.Cells · 2026Article
- Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.bioRxiv : the preprint server for biology · 2026Article
- Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray.Molecular pharmacology · 2025Article
- Modulatory Effects of CB1 Receptors on Cognitive Performance in Rat Model of Empathic Pain.Basic and clinical neuroscience · 2025Article
- A systematic review of the pain-related emotional and cognitive impairments in chronic inflammatory pain induced by CFA injection and its mechanism.IBRO neuroscience reports · 2025Review
- Specific Activation of Dopamine Receptor D1 Expressing Neurons in the PrL Alleviates CSDS-Induced Anxiety-Like Behavior Comorbidity with Postoperative Hyperalgesia in Male Mice.Molecular neurobiology · 2025Article
- Peripheral inflammation is accompanied by cerebral hypoperfusion in mice.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- General anesthesia activates a central anxiolytic center in the BNST.Cell reports · 2024Article
- The Antidepressant- and Anxiolytic-Like Effects of the Phosphodiesterase Type-5 Inhibitor Tadalafil are Associated with the Modulation of the Gut-Brain Axis During CNS Autoimmunity.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Acute restraint stress regulates brain DNMT3a and promotes defensive behaviors in male rats.Neuroscience letters · 2024Article
- Recent advances in anxiety disorders: Focus on animal models and pathological mechanisms.Animal models and experimental medicine · 2023Review
- The influence of the enriched environment in different periods on neonatal maternal separation-induced visceral pain, anxiousness, and depressive behaviors.Translational pediatrics · 2022Article
- Catalpol ameliorates CFA-induced inflammatory pain by targeting spinal cord and peripheral inflammation.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic pain increases the risk of developing anxiety, with limbic areas being likely neurological substrates. Despite high clinical relevance, little is known about the precise behavioral, hormonal, and brain neuroplastic correlates of anxiety in the context of persistent pain. Previous studies have shown that decreased nociceptive thresholds in chronic pain models are paralleled by anxiety-like behavior in rats, but there are conflicting ideas regarding its effects on the stress response and circulating corticosterone levels. Even less is known about the molecular mechanisms through which the brain encodes pain-related anxiety. This study examines how persistent inflammatory pain in a rat model would impact anxiety-like behaviors and corticosterone release, and whether these changes would be reflected in levels of global DNA methylation in brain areas involved in stress regulation. Complete Freund's adjuvant (CFA) or saline was administered in the right hindpaw of adult male Wistar rats. Behavioral testing included the measurement of nociceptive thresholds (digital anesthesiometer), motor function (open field test), and anxiety-like behaviors (elevated plus maze and the dark-light box test). Corticosterone was measured via radioimmunoassay. Global DNA methylation (enzyme immunoassay) as well as DNMT3a levels (western blotting) were quantified in the amygdala, prefrontal cortex, and ventral hippocampus. CFA administration resulted in persistent reduction in nociceptive threshold in the absence of locomotor abnormalities. Increased anxiety-like behaviors were observed in the elevated plus maze and were accompanied by increased blood corticosterone levels 10 days after pain induction. Global DNA methylation was decreased in the amygdala, with no changes in DNMT3a abundance in any of the regions examined. Persistent inflammatory pain promotes anxiety -like behaviors, HPA axis activation, and epigenetic regulation through DNA methylation in the amygdala. These findings describe a molecular mechanism that links pain and stress in a well-characterized rodent model.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.