ArticlePain2017
Neuron-restrictive silencer factor-mediated downregulation of μ-opioid receptor contributes to the reduced morphine analgesia in bone cancer pain.
Article in Pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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.
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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals with pharmacological significance.Translational psychiatry · 2022Pooled it
- The Dynamic Roles of Repressor Element 1-Silencing Transcription Factor (REST): A Double-Edged Sword in Neural Health and Disease.Molecular neurobiology · 2025Review
- [Clinical pharmacology of opioid analgesics].Schmerz (Berlin, Germany) · 2025Review
- Article
- Optimization strategies for mesenchymal stem cell-based analgesia therapy: a promising therapy for pain management.Stem cell research & therapy · 2024Review
- REST Is Not Resting: REST/NRSF in Health and Disease.Biomolecules · 2023Review
- The Downregulation of Opioid Receptors and Neuropathic Pain.International journal of molecular sciences · 2023Review
- Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice.Brain sciences · 2023Article
- Lactobacillus rhamnosus GG and butyrate supplementation in rats with bone cancer reduces mechanical allodynia and increases expression of μ-opioid receptor in the spinal cord.Frontiers in molecular neuroscience · 2023Article
- Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.Frontiers in cell and developmental biology · 2022Review
- Mechanisms of cancer pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Epigenetics Involvement in Oxaliplatin-Induced Potassium Channel Transcriptional Downregulation and Hypersensitivity.Molecular neurobiology · 2021Article
- Clinical Efficacy of Controlled-Release Morphine Tablets Combined with Celecoxib in Pain Management and the Effects on WNK1 Expression.Clinics (Sao Paulo, Brazil) · 2021Article
- Antinociceptive effect of intrathecal injection of miR-9-5p modified mouse bone marrow mesenchymal stem cells on a mouse model of bone cancer pain.Journal of neuroinflammation · 2020Article
- Repressor element 1-silencing transcription factor drives the development of chronic pain states.Pain · 2019Article
- Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.Frontiers in pharmacology · 2018Article
- Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway.Experimental biology and medicine (Maywood, N.J.) · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively. Additionally, chromatin immunoprecipitation assays were used to detect NRSF binding to the promoter of MOR. Furthermore, NRSF was genetically knocked out by antisense oligodeoxynucleotide, and the expression of MOR and the effect of morphine were subsequently analyzed. Our results indicated that in a sarcoma murine model, NRSF expression is upregulated in dorsal root ganglion neurons, and the expression of NRSF mRNA is significantly negatively correlated with MOR mRNA expression. Additionally, chromatin immunoprecipitation analysis revealed that NRSF binding to the neuron-restrictive silencer element within the promoter area of the MOR gene is promoted with a hypoacetylation state of histone H3 and H4. Furthermore, genetically knocking down NRSF with antisense oligodeoxynucleotide rescued the expression of MOR and potentiated the systemic morphine analgesia. The present results suggest that in sarcoma-induced bone cancer pain, NRSF-induced downregulation of MOR is involved in the reduction of morphine analgesia. Epigenetically, up-regulation of MOR could substantially improve the effect of system delivery of morphine.
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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.