ArticleMolecular pain2016
Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ.
Article in Molecular pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- The nociceptor primary cilium.Brain : a journal of neurology · 2026Review
- MicroRNA-219 in the central nervous system: a potential theranostic approach.Research in pharmaceutical sciences · 2024Review
- Targeting exosomal double-stranded RNA-TLR3 signaling pathway attenuates morphine tolerance and hyperalgesia.Cell reports. Medicine · 2024Article
- BDNF Modulation by microRNAs: An Update on theCells · 2024Review
- The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation.Biomolecules · 2024Review
- Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia.Metabolic brain disease · 2023Article
- BDNF and its signaling in cancer.Journal of cancer research and clinical oncology · 2023Review
- Sonic Hedgehog Signaling Pathway: A Role in Pain Processing.Neurochemical research · 2023Review
- Extracellular vesicle-mediated delivery of anti-miR-106b inhibits morphine-induced primary ciliogenesis in the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Orbitofrontal cortex microRNAs support long-lasting heroin seeking behavior in male rats.Translational psychiatry · 2023Article
- Integrated omics analysis reveals the epigenetic mechanism of visceral hypersensitivity in IBS-D.Frontiers in pharmacology · 2023Article
- CaMKII Splice Variants in Vascular Smooth Muscle Cells: The Next Step or Redundancy?International journal of molecular sciences · 2022Review
- microRNA expression levels in the nucleus accumbens correlate with morphine-taking but not morphine-seeking behaviour in male rats.The European journal of neuroscience · 2022Article
- Epigenetic Alterations in Prescription Opioid Misuse: New Strategies for Precision Pain Management.Genes · 2021Review
- The Colonic Mucosal MicroRNAs, MicroRNA-219a-5p, and MicroRNA-338-3p Are Downregulated in Irritable Bowel Syndrome and Are Associated With Barrier Function and MAPK Signaling.Gastroenterology · 2021Article
- Role of Micro-RNA for Pain After Surgery: Narrative Review of Animal and Human Studies.Anesthesia and analgesia · 2020Review
- Morphine modulates the expression of mu-opioid receptor exon 5-associated full-length C-terminal splice variants by upregulating miR-378a-3p.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- MicroRNA-219a-5p suppresses intestinal inflammation through inhibiting Th1/Th17-mediated immune responses in inflammatory bowel disease.Mucosal immunology · 2020Article
- Differential Expression and Bioinformatic Analysis of the circRNA Expression in Migraine Patients.BioMed research international · 2020Article
- Hsa-miR-34a-5p and hsa-miR-375 as Biomarkers for Monitoring the Effects of Drug Treatment for Migraine Pain in Children and Adolescents: A Pilot Study.Journal of clinical medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreasing evidence suggests that microRNAs are functionally involved in the initiation and maintenance of pain hypersensitivity, including chronic morphine analgesic tolerance, through the posttranscriptional regulation of pain-related genes. We have previously demonstrated that miR-219 regulates inflammatory pain in the spinal cord by targeting calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ). However, whether miR-219 regulates CaMKIIγ expression in the dorsal root ganglia to mediate morphine tolerance remains unclear.
resultsMiR-219 expression was downregulated and CaMKIIγ expression was upregulated in mouse dorsal root ganglia following chronic morphine treatment. The changes in miR-219 and CaMKIIγ expression closely correlated with the development of morphine tolerance, which was measured using the reduction of percentage of maximum potential efficiency to thermal stimuli. Morphine tolerance was markedly delayed by upregulating miR-219 expression using miR-219 mimics or downregulating CaMKIIγ expression using CaMKIIγ small interfering RNA. The protein and mRNA expression of brain-derived neurotrophic factor were also induced in dorsal root ganglia by prolonged morphine exposure in a time-dependent manner, which were transcriptionally regulated by miR-219 and CaMKIIγ. Scavenging brain-derived neurotrophic factor via tyrosine receptor kinase B-Fc partially attenuated morphine tolerance. Moreover, functional inhibition of miR-219 via miR-219-sponge in naive mice elicited thermal hyperalgesia and spinal neuronal sensitization, which were both suppressed by CaMKIIγ small interfering RNA or tyrosine receptor kinase B-Fc.
conclusionsThese results demonstrate that miR-219 contributes to the development of chronic tolerance to morphine analgesia in mouse dorsal root ganglia by targeting CaMKIIγ and enhancing CaMKIIγ-dependent brain-derived neurotrophic factor expression.
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