ArticleJournal of neuroinflammation2022
The YTHDF1-TRAF6 pathway regulates the neuroinflammatory response and contributes to morphine tolerance and hyperalgesia in the periaqueductal gray.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Functional Role of ALKBH5 in Kidney Injury: Insights Into Mechanisms and Therapeutic Potential.Journal of cellular biochemistry · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- Decoding the role of mNeurochemistry international · 2025Review
- An Investigation of the RNA Modification mInternational journal of molecular sciences · 2025Article
- The Role and Mechanism of TRIM13 Regulation of TRAF6 Ubiquitination in the Synergy of Inflammatory Responses and Neurotoxicity Induced by METH and HIV- 1 Tat Protein in Astrocytes.Neurotoxicity research · 2025Article
- Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4.European journal of medical research · 2025Article
- YTHDF1 in periaqueductal gray inhibitory neurons contributes to morphine withdrawal responses in mice.BMC medicine · 2024Article
- Article
- Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study.Frontiers in microbiology · 2024Article
- No significant change of NBrain and behavior · 2024Article
- METTL14 Regulates the m6A Modification of TRAF6 to Suppress Mitochondrial Dysfunction and Ferroptosis in Dopaminergic Neurons via the cGAS-STING Pathway.Current molecular medicine · 2024Article
- Puerarin improves the comorbidity of chronic pain and depression by binding with Bax and reducing mitochondrial dysfunction.Molecular painArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Long-term use of opioids such as morphine has negative side effects, such as morphine analgesic tolerance and morphine-induced hyperalgesia (MIH). These side effects limit the clinical use and analgesic efficacy of morphine. Elucidation of the mechanisms and identification of feasible and effective methods or treatment targets to solve this clinical phenomenon are important. Here, we discovered that YTHDF1 and TNF receptor-associated factor 6 (TRAF6) are crucial for morphine analgesic tolerance and MIH. The m6A reader YTHDF1 positively regulated the translation of TRAF6 mRNA, and chronic morphine treatments enhanced the m6A modification of TRAF6 mRNA. TRAF6 protein expression was drastically reduced by YTHDF1 knockdown, although TRAF6 mRNA levels were unaffected. By reducing inflammatory markers such as IL-1β, IL-6, TNF-α and NF-κB, targeted reduction of YTHDF1 or suppression of TRAF6 activity in ventrolateral periaqueductal gray (vlPAG) slows the development of morphine analgesic tolerance and MIH. Our findings provide new insights into the mechanism of morphine analgesic tolerance and MIH indicating that YTHDF1 regulates inflammatory factors such as IL-1β, IL-6, TNF-α and NF-κB by enhancing TRAF6 protein expression.
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