ArticleJournal of neuroinflammation2021
Calcitonin gene-related peptide regulates spinal microglial activation through the histone H3 lysine 27 trimethylation via enhancer of zeste homolog-2 in rats with neuropathic pain.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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
30 citing papers in PubMed, 42 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Spinal neuronal TLR4-induced enhancement of nociceptive signals contributes to myocardial ischemia/reperfusion injury.Basic research in cardiology · 2026Article
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- CGRP reception potentiates anxiety in an influenza A derived immune engram.bioRxiv : the preprint server for biology · 2026Article
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Temporal regulation of macrophage polarization by abnormally innervated CGRP + Sensory nerves following spinal cord injury.Cellular and molecular life sciences : CMLS · 2026Review
- CGRP: the immune system's double agent - context-dependent roles in inflammation, resolution and cancer.Frontiers in immunology · 2026Review
- Article
- Enhancer profiling uncovers Jmjd1c as an essential suppressor in neuropathic pain by targeting Socs3.Genes & diseases · 2025Article
- Review
- The Role of Methylation Modification in Neural Injury and Repair.International journal of molecular sciences · 2025Review
- Gut neuropeptide involvement in Parkinson's disease.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Article
- Evaluation of Ocular Irritation Sensitivity: Implications of Clinical Parameters, Pain Sensitivity, and Tear Neuromediator Profiles.Journal of clinical medicine · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Monoclonal Antibody Targeting CGRP Relieves Cisplatin-Induced Neuropathic Pain by Attenuating Neuroinflammation.Neurotoxicity research · 2024Article
- Pulmonary neuroendocrine cells: crucial players in respiratory function and airway-nerve communication.Frontiers in neuroscience · 2024Review
- The Epigenetics of Neuropathic Pain: A Systematic Update.International journal of molecular sciences · 2023Review
- Genome-wide Analysis of Histone H3 Lysine 27 Trimethylation Profiles in Sciatic Nerve of Chronic Constriction Injury Rats.Neurochemical research · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCalcitonin gene-related peptide (CGRP) as a mediator of microglial activation at the transcriptional level may facilitate nociceptive signaling. Trimethylation of H3 lysine 27 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that regulates inflammatory-related gene expression after peripheral nerve injury. In this study, we explored the relationship between CGRP and H3K27me3 in microglial activation after nerve injury, and elucidated the underlying mechanisms in the pathogenesis of chronic neuropathic pain.
methodsMicroglial cells (BV2) were treated with CGRP and differentially enrichments of H3K27me3 on gene promoters were examined using ChIP-seq. A chronic constriction injury (CCI) rat model was used to evaluate the role of CGRP on microglial activation and EZH2/H3K27me3 signaling in CCI-induced neuropathic pain.
resultsOverexpressions of EZH2 and H3K27me3 were confirmed in spinal microglia of CCI rats by immunofluorescence. CGRP treatment induced the increased of H3K27me3 expression in the spinal dorsal horn and cultured microglial cells (BV2) through EZH2. ChIP-seq data indicated that CGRP significantly altered H3K27me3 enrichments on gene promoters in microglia following CGRP treatment, including 173 gaining H3K27me3 and 75 losing this mark, which mostly enriched in regulation of cell growth, phagosome, and inflammation. qRT-PCR verified expressions of representative candidate genes (TRAF3IP2, BCL2L11, ITGAM, DAB2, NLRP12, WNT3, ADAM10) and real-time cell analysis (RTCA) verified microglial proliferation. Additionally, CGRP treatment and CCI increased expressions of ITGAM, ADAM10, MCP-1, and CX3CR1, key mediators of microglial activation in spinal dorsal horn and cultured microglial cells. Such increased effects induced by CCI were suppressed by CGRP antagonist and EZH2 inhibitor, which were concurrently associated with the attenuated mechanical and thermal hyperalgesia in CCI rats.
conclusionOur findings highly indicate that CGRP is implicated in the genesis of neuropathic pain through regulating microglial activation via EZH2-mediated H3K27me3 in the spinal dorsal horn.
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.