Spinal ceramide and neuronal apoptosis in morphine antinociceptive tolerance

Leesa Bryant, Tim Doyle, Zhoumo Chen, Salvatore Cuzzocrea, Emanuela Masini, M. Cristina Vinci, Emanuela Esposito, Emanuela Mazzon, Daniela Nicoleta Petrusca, Irina Petrache, Daniela Salvemini

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Opiates, like morphine, are the most effective analgesics for treating acute and chronic severe pain, but their use is limited by the development of analgesic tolerance and hypersensitivity to innocuous and noxious stimuli. Because opioids are a mainstay of pain management, restoring their efficacy has great clinical importance. We have recently demonstrated that spinal ceramide, a sphingolipid signaling molecule plays a central role in the development of morphine antinociceptive tolerance. We now report that ceramide upregulation in dorsal horn tissues in response to chronic morphine administration is associated with significant neuronal apoptosis. Inhibition of ceramide biosynthesis attenuated both the increase in neuronal apoptosis and the development of antinociceptive tolerance. These findings indicate that spinal ceramide upregulation is a key pro-apoptotic event that occurs upstream of the development of morphine antinociceptive tolerance and support the rationale for development of inhibitors of ceramide biosynthesis as adjuncts to opiates for the management of chronic pain.

Original languageEnglish (US)
Pages (from-to)49-53
Number of pages5
JournalNeuroscience Letters
Volume463
Issue number1
DOIs
StatePublished - Sep 29 2009

Keywords

  • Ceramide
  • Morphine tolerance
  • Neuronal apoptosis
  • Nitroxidative stress
  • Peroxynitrite

ASJC Scopus subject areas

  • Neuroscience(all)

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    Bryant, L., Doyle, T., Chen, Z., Cuzzocrea, S., Masini, E., Vinci, M. C., Esposito, E., Mazzon, E., Petrusca, D. N., Petrache, I., & Salvemini, D. (2009). Spinal ceramide and neuronal apoptosis in morphine antinociceptive tolerance. Neuroscience Letters, 463(1), 49-53. https://doi.org/10.1016/j.neulet.2009.07.051