ArticleNeuroscience2009
Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance.
Article in Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
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- Involvement of Oxidative Stress and Nutrition in the Anatomy of Orofacial Pain.International journal of molecular sciences · 2023Review
- Antisense oligodeoxynucleotides against dynamin-related protein 1 reduce remifentanil-induced hyperalgesia by modulating spinal N-methyl-D-aspartate receptor expression in rats.The Korean journal of pain · 2023Article
- Reactive Oxygen Species (ROS) are Critical for Morphine Exacerbation of HIV-1 gp120-Induced Pain.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration.Antioxidants (Basel, Switzerland) · 2020Article
- Supraphysiologic-dose anabolic-androgenic steroid use: A risk factor for dementia?Neuroscience and biobehavioral reviews · 2019Review
- Mn Porphyrin-Based Redox-Active Drugs: Differential Effects as Cancer Therapeutics and Protectors of Normal Tissue Against Oxidative Injury.Antioxidants & redox signaling · 2018Review
- Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.Inflammopharmacology · 2016Article
- A comprehensive evaluation of catalase-like activity of different classes of redox-active therapeutics.Free radical biology & medicine · 2015Article
- Satureja khuzestanica prevents the development of morphine analgesic tolerance through suppression of spinal glial cell activation in rats.Journal of natural medicines · 2015Article
- Rational design of superoxide dismutase (SOD) mimics: the evaluation of the therapeutic potential of new cationic Mn porphyrins with linear and cyclic substituents.Inorganic chemistry · 2014Article
- SOD therapeutics: latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways.Antioxidants & redox signaling · 2014Review
- Ginger (zingiber officinale roscoe) prevents morphine-induced addictive behaviors in conditioned place preference test in rats.Addiction & health · 2014Article
- Morphine as a Potential Oxidative Stress-Causing Agent.Mini-reviews in organic chemistry · 2013Article
- NADPH-oxidase 2 activation promotes opioid-induced antinociceptive tolerance in mice.Neuroscience · 2013Article
- Design, mechanism of action, bioavailability and therapeutic effects of mn porphyrin-based redox modulators.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2013Review
- A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.Free radical biology & medicine · 2012Article
- Manganese superoxide dismutase, MnSOD and its mimics.Biochimica et biophysica acta · 2012Review
- Anti-superoxide and anti-peroxynitrite strategies in pain suppression.Biochimica et biophysica acta · 2012Article
- Design of Mn porphyrins for treating oxidative stress injuries and their redox-based regulation of cellular transcriptional activities.Amino acids · 2012Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Effective treatment of chronic pain with morphine is limited by decreases in the drug's analgesic action with chronic administration (antinociceptive tolerance). Because opioids are mainstays of pain management, restoring their efficacy has great clinical importance. We have recently reported that formation of peroxynitrite (ONOO(-), PN) in the dorsal horn of the spinal cord plays a critical role in the development of morphine antinociceptive tolerance and have further documented that nitration and enzymatic inactivation of mitochondrial superoxide dismutase (MnSOD) at that site provides a source for this nitroxidative species. We now report for the first time that antinociceptive tolerance in mice is also associated with the inactivation of MnSOD at supraspinal sites. Inactivation of MnSOD led to nitroxidative stress as evidenced by increased levels of products of oxidative DNA damage and activation of the nuclear factor poly (ADP-ribose) polymerase in whole brain homogenates. Co-administration of morphine with potent Mn porphyrin-based peroxynitrite scavengers, Mn(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+) and Mn(III) 5,10,15,20-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP5+) (1) restored the enzymatic activity of MnSOD, (2) attenuated PN-derived nitroxidative stress, and (3) blocked the development of morphine-induced antinociceptive tolerance. The more lipophilic analogue, MnTnHex-2-PyP5+ was able to cross the blood-brain barrier at higher levels than its lipophylic counterpart MnTE-2-PyP5+ and was about 30-fold more efficacious. Collectively, these data suggest that PN-mediated enzymatic inactivation of supraspinal MnSOD provides a source of nitroxidative stress, which in turn contributes to central sensitization associated with the development of morphine antinociceptive tolerance. These results support our general contention that PN-targeted therapeutics may have potential as adjuncts to opiates in pain management.
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