Opioids, NSAIDS and 5-lipoxygenase inhibitors act synergistically in brain via arachidonic acid metabolism

M. J. Christie, C. W. Vaughan, S. L. Ingram

Research output: Contribution to journalShort survey

49 Scopus citations


We have established that μ-opioid receptor activation causes a presynaptic inhibition of neurotransmitter release that is mediated by 12-lipoxygenase metabolites of arachidonic acid in midbrain neurons. We further demonstrated that the efficacy of opioids was enhanced synergistically by treatment of brain neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism; cyclooxygenase (COX-1) and 5-lipoxygenase. These findings explain a mechanism of analgesic action of NSAIDs in the central nervous system that is both independent of prostanoid release and inhibited by opioid antagonists, as well as the synergistic interaction of opioids with NSAIDs. These findings also suggest new avenues for development of centrally active medications involving combinations of lowered doses of opioids and specific 5-lipoxygenase inhibitors.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalInflammation Research
Issue number1
StatePublished - Feb 2 1999



  • 5-Lipoxygenase
  • Arachidonic acid
  • Opioid
  • Pain

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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