ArticlePloS one2014
Phosphoproteomics and bioinformatics analyses of spinal cord proteins in rats with morphine tolerance.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Article
- Morphine produces better thermal analgesia in young Huntington mice and are associated with less neuroinflammation in spinal cord.Journal of the Chinese Medical Association : JCMA · 2021Article
- The cellular basis of fetal endoplasmic reticulum stress and oxidative stress in drug-induced neurodevelopmental deficits.Neurobiology of stress · 2019Review
- The Proteomics of Intrathecal Analgesic agents for Chronic Pain.Current neuropharmacology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
introductionMorphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance.
methodsTo better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins.
resultsOur proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism.
conclusionsRepeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance.
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