Spinal NADPH oxidase is a source of superoxide in the development of morphine-induced hyperalgesia and antinociceptive tolerance.

Neuroscience Letters
Tim DoyleDaniela Salvemini

Abstract

The role of superoxide and its active byproduct peroxynitrite as mediators of nociceptive signaling is emerging. We have recently reported that nitration and inactivation of spinal mitochondrial superoxide dismutase (MnSOD) provides a critical source of these reactive oxygen and nitrogen species during central sensitization associated with the development of morphine-induced hyperalgesia and antinociceptive tolerance. In this study, we demonstrate that activation of spinal NADPH oxidase is another critical source for superoxide generation. Indeed, the development of morphine-induced hyperalgesia and antinociceptive tolerance was associated with increased activation of NADPH oxidase and superoxide release. Co-administration of morphine with systemic delivery of two structurally unrelated NADPH oxidase inhibitors namely apocynin or diphenyleneiodonium (DPI), blocked NADPH oxidase activation and the development of hyperalgesia and antinociceptive tolerance at doses devoid of behavioral side effects. These results suggest that activation of spinal NADPH oxidase contributes to the development of morphine-induced hyperalgesia and antinociceptive tolerance. The role of spinal NADPH oxidase was confirmed by showing that intrathecal del...Continue Reading

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Citations

May 15, 2013·Molecular Neurobiology·María Rodríguez-Muñoz, Javier Garzón
Jun 5, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sheu-Ran ChoiJang-Hern Lee
May 9, 2012·Antioxidants & Redox Signaling·Pilar Sánchez-BlázquezJavier Garzón
Nov 19, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carolina MuscoliDaniela Salvemini
May 4, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Timothy DoyleDaniela Salvemini
May 28, 2013·Antioxidants & Redox Signaling·Huaxin ShengDavid S Warner
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Nov 14, 2012·Pharmacology & Therapeutics·Wiebke Kallenborn-GerhardtAchim Schmidtko
Oct 9, 2012·Peptides·Richard J Bodnar
Feb 1, 2011·Free Radical Biology & Medicine·Daniela SalveminiWilliam L Neumann
Apr 3, 2015·Headache·Peter M GraceLinda R Watkins
Apr 9, 2015·Journal of Pharmaceutical and Biomedical Analysis·Shuai MaYong-Xiang Wang
Jan 6, 2015·Antioxidants & Redox Signaling·María Rodríguez-MuñozJavier Garzón
Jun 9, 2016·British Journal of Pharmacology·G TeixeiraJ M Wood
Nov 16, 2016·Trends in Neurosciences·Peter M GraceLinda R Watkins
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Jun 26, 2017·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Ajeet Kumar Singh, Manjula Vinayak
Sep 7, 2018·Cellular and Molecular Neurobiology·Susana Laura GonzálezAyikoe Guy Mensah-Nyagan
Oct 23, 2015·Cardiovascular Diabetology·Mingge DingXiaoming Wang

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