ArticleThe Journal of pharmacology and experimental therapeutics2009
Spinal ceramide modulates the development of morphine antinociceptive tolerance via peroxynitrite-mediated nitroxidative stress and neuroimmune activation.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 42 papers.
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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
42 citing papers in PubMed, 71 citations in OpenAlex.
- Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024Review
- Sleep-mediated regulation of reward circuits: implications in substance use disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells.Molecules (Basel, Switzerland) · 2022Article
- Effects of valsartan on morphine tolerance and dependence in rats.Research in pharmaceutical sciences · 2021Article
- Synthetic Secoisolariciresinol Diglucoside Attenuates Established Pain, Oxidative Stress and Neuroinflammation in a Rodent Model of Painful Radiculopathy.Antioxidants (Basel, Switzerland) · 2020Article
- Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics.Trends in pharmacological sciences · 2020Review
- Supraphysiologic-dose anabolic-androgenic steroid use: A risk factor for dementia?Neuroscience and biobehavioral reviews · 2019Review
- The effect of metformin on morphine analgesic tolerance and dependence in rats.Research in pharmaceutical sciences · 2018Article
- The role of sphingolipids in psychoactive drug use and addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- A computational strategy for finding novel targets and therapeutic compounds for opioid dependence.PloS one · 2018Article
- The Contribution of the Descending Pain Modulatory Pathway in Opioid Tolerance.Frontiers in neuroscience · 2018Article
- Involvement of neuronal TGF-β activated kinase 1 in the development of tolerance to morphine-induced antinociception in rat spinal cord.British journal of pharmacology · 2015Article
- Current gene therapy using viral vectors for chronic pain.Molecular pain · 2015Review
- Satureja khuzestanica prevents the development of morphine analgesic tolerance through suppression of spinal glial cell activation in rats.Journal of natural medicines · 2015Article
- Review
- Delay of morphine tolerance by palmitoylethanolamide.BioMed research international · 2015Article
- The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1.The Journal of biological chemistry · 2014Article
- Cyclooxygenase-2 and inflammation mediators have a crucial role in reflux-related esophageal histological changes and Barrett's esophagus.Digestive diseases and sciences · 2014Article
- A peroxynitrite decomposition catalyst prevents mechanical allodynia and NMDA receptor activation in the hind-paw ischemia reperfusion injury rats.Experimental and therapeutic medicine · 2014Article
- Anti-inflammatory action of lipid nanocarrier-delivered myriocin: therapeutic potential in cystic fibrosis.Biochimica et biophysica acta · 2014Article
Corrections and comments
- Expression of concern
- Expression of concern
Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
The effective treatment of pain is typically limited by a decrease in the pain-relieving action of morphine that follows its chronic administration (tolerance). Therefore, restoring opioid efficacy is of great clinical importance. In a murine model of opioid antinociceptive tolerance, repeated administration of morphine significantly stimulated the enzymatic activities of spinal cord serine palmitoyltransferase, ceramide synthase, and acid sphingomyelinase (enzymes involved in the de novo and sphingomyelinase pathways of ceramide biosynthesis, respectively) and led to peroxynitrite-derive nitroxidative stress and neuroimmune activation [activation of spinal glial cells and increase formation of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6]. Inhibition of ceramide biosynthesis with various pharmacological inhibitors significantly attenuated the increase in spinal ceramide production, nitroxidative stress, and neuroimmune activation. These events culminated in a significant inhibition of the development of morphine antinociceptive tolerance at doses devoid of behavioral side effects. Our findings implicate ceramide as a key upstream signaling molecule in the development of morphine antinociceptive tolerance and provide the rationale for development of inhibitors of ceramide biosynthesis as adjuncts to opiates for the management of chronic pain.
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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.