ArticleGene2018
Pharmacological targeting of the mammalian clock reveals a novel analgesic for osteoarthritis-induced pain.
Article in Gene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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
19 citing papers in PubMed, 43 citations in OpenAlex.
- Nociceptor circadian clock genes control excitability and pain perception in mice in a sex- and time-dependent manner.Nature communications · 2026Article
- Sleep and circadian rhythm disturbances as risk and progression factors for multiple chronic overlapping pain conditions: a protocol for a longitudinal study.Pain reports · 2024Article
- SR9009 attenuates inflammation-related NPMSC pyroptosis and IVDD through NR1D1/NLRP3/IL-1β pathway.iScience · 2024Article
- Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage.Science advances · 2024Article
- Medium- and Long-Term Effects of Insomnia Severity and Circadian Preference on Pain and Emotional Distress Among Individuals With Chronic Pain.The journal of pain · 2023Article
- Blocking circadian clock factor Rev-erbα inhibits growth plate chondrogenesis via up-regulating MAPK-ERK1/2 pathway.Cell cycle (Georgetown, Tex.) · 2023Article
- The disruptive relationship among circadian rhythms, pain, and opioids.Frontiers in neuroscience · 2023Review
- Article
- Dark-light cycle disrupts bone metabolism and suppresses joint deterioration in osteoarthritic rats.Arthritis research & therapy · 2022Article
- Article
- Article
- Circadian rhythms and pain.Neuroscience and biobehavioral reviews · 2021Review
- Drivers of phenotypic variation in cartilage: Circadian clock genes.Journal of cellular and molecular medicine · 2021Review
- Implications of Disrupted Circadian Rhythms on Pain.Journal of psychiatry and brain science · 2021Article
- Proinflammatory Cytokines Perturb Mouse and Human Pancreatic Islet Circadian Rhythmicity and Induce Uncoordinated β-Cell Clock Gene Expression via Nitric Oxide, Lysine Deacetylases, and Immunoproteasomal Activity.International journal of molecular sciences · 2020Article
- Circadian regulation of chemotherapy-induced peripheral neuropathic pain and the underlying transcriptomic landscape.Scientific reports · 2020Article
- Modeling the daily rhythm of human pain processing in the dorsal horn.PLoS computational biology · 2019Article
- Blockade of Vascular Endothelial Growth Factor Receptor-1 (Flt-1), Reveals a Novel Analgesic For Osteoarthritis-Induced Joint Pain.Gene reports · 2018Article
- The contribution of clock genes BMAL1 and PER2 in osteoarthritis-associated pain.Neurobiology of pain (Cambridge, Mass.)Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Environmental disruption of the circadian rhythm is linked with increased pain due to osteoarthritis (OA). We aimed to characterize the role of the clock gene in OA-induced pain more systemically using both genetic and pharmacological approaches. Genetically modified mice, (bmal1f/fNav1.8CreERT mice), generated by deleting the critical clock gene, bmal1, from Nav1.8 sensory neurons, were resistant to the development of mechanical hyperalgesia associated with OA induced by partial medial meniscectomy (PMM) of the knee. In wild-type mice, induction of OA by PMM surgery led to a substantial increase in BMAL1 expression in DRG neurons. Interestingly, pharmacological activation of the REV-ERB (a negative regulator of bmal1 transcription) with SR9009 resulted in reduction of BMAL1 expression, and a significant decrease in mechanical hyperalgesia associated with OA. Cartilage degeneration was also significantly reduced in mice treated with the REV-ERB agonist SR9009. Based on these data, we also assessed the effect of pharmacological activation of REV-ERB using a model of environmental circadian disruption with its associated mechanical hyperalgesia, and noted that SR9009 was an effective analgesic in this model as well. Our data clearly demonstrate that genetic disruption of the molecular clock, via deletion of bmal1 in the sensory neurons of the DRG, decreases pain in a model of OA. Furthermore, pharmacological activation of REV-ERB leading to suppression of BMAL1 expression may be an effective method for treating OA-related pain, as well as to reduce joint damage associated with this disease.
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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.