ArticleMolecular neurobiology2019
Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus Accumbens.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Circadian pain patterns in human pain conditions - A systematic review.Pain practice : the official journal of World Institute of Pain · 2023Pooled it
- Metabolite-neuro-immune relay in chronic pain: spatial-temporal lactate, succinate and itaconate signalling as drivers of glial reprogramming and neuronal sensitisation.Frontiers in pharmacology · 2026Review
- Casomorphine-10 (CM-10) Peptide Orchestrates Circadian and Neurodevelopmental Gene Clusters via δ-Opioid Receptor Signaling: Insights from Transcriptome Analysis with δ-Opioid Receptor-Expressing HEK293 Cells.Life (Basel, Switzerland) · 2025Article
- Disrupted circadian rhythms and opioid-mediated adverse effects: Bidirectional relationship and putative mechanisms.Journal of neuroendocrinology · 2025Review
- Peroxisome, neuropeptide, and inflammation signaling pathways uniquely impacted by opioid exposure in the hypothalamus of males and females.Molecular and cellular neurosciences · 2025Article
- Article
- Circadian Rhythms and Pain: A Narrative Review on Clock Genes and Circadian-Based Interventions.Journal of pain research · 2025Review
- Platelet/high-density lipoprotein cholesterol ratio as a biomarker of depression in individuals with chronic opioid use.Frontiers in psychiatry · 2025Article
- Sex- and Substance-Specific Associations of Circadian-Related Genes with Addiction in the UK Biobank Cohort Implicate Neuroplasticity Pathways.Brain sciences · 2024Article
- Immune and metabolic challenges induce changes in pain sensation and related pathways in the hypothalamus.Physiological genomics · 2024Article
- Restoration of the Activity of the Prefrontal Cortex to the Nucleus Accumbens Core Pathway Relieves Fentanyl-Induced Hyperalgesia in Male Rats.Journal of pain research · 2024Article
- Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome.Journal of proteome research · 2023Article
- Article
- PACAP-PAC1 receptor inhibition is effective in opioid induced hyperalgesia and medication overuse headache models.iScience · 2023Article
- Prenatal and postnatal challenges affect the hypothalamic molecular pathways that regulate hormonal levels.PloS one · 2023Article
- Sex-specific role of the circadian transcription factor NPAS2 in opioid tolerance, withdrawal and analgesia.Genes, brain, and behavior · 2022Article
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- Enhanced Understanding of Molecular Interactions and Function Underlying Pain Processes Through Networks of Transcript Isoforms, Genes, and Gene Families.Advances and applications in bioinformatics and chemistry : AABC · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The benefits of opioid-based treatments to mitigate chronic pain can be hindered by the side effects of opioid-induced hyperalgesia (OIH) that can lead to higher consumption and risk of addiction. The present study advances the understanding of the molecular mechanisms associated with OIH by comparing mice presenting OIH symptoms in response to chronic morphine exposure (OIH treatment) relative to control mice (CON treatment). Using RNA-Seq profiles, gene networks were inferred in the trigeminal ganglia (TG), a central nervous system region associated with pain signaling, and in the nucleus accumbens (NAc), a region associated with reward dependency. The biological process of nucleic acid processing was over-represented among the 122 genes that exhibited a region-dependent treatment effect. Within the 187 genes that exhibited a region-independent treatment effect, circadian rhythm processes were enriched among the genes over-expressed in OIH relative to CON mice. This enrichment was supported by the differential expression of the period circadian clock 2 and 3 genes (Per2 and Per3). Transcriptional regulators in the PAR bZip family that are influenced by the circadian clock and that modulate neurotransmission associated with pain and drug addiction were also over-expressed in OIH relative to CON mice. Also notable was the under-expression in OIH relative to CON mice of the Toll-like receptor, nuclear factor-kappa beta, and interferon gamma genes and enrichment of the adaptive immune processes. The results from the present study offer insights to advance the effective use of opioids for pain management while minimizing hyperalgesia.
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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.