• Pain · Feb 2021

    Differential actions of indomethacin: clinical relevance in headache.

    • Oliver Summ, Anna P Andreou, Simon Akerman, Philip R Holland, Jan Hoffmann, and Peter J Goadsby.
    • Headache Group-Department of Neurology, University of California, San Francisco, San Francisco, CA, United States . Dr. Summ is now with the Department of Neurology and Research Center of Neurosensory Science, Carl von Ossietzky University Oldenburg, Oldenburg, Germany . Dr. Andreou is now with the Headache Research-Wolfson CARD, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom . Dr. Akerman is now with the Department of Neural and Pain Sciences, University of Maryland Baltimore, Baltimore, MD, United States.
    • Pain. 2021 Feb 1; 162 (2): 591599591-599.

    AbstractNonsteroidal anti-inflammatory drugs, cyclooxygenase inhibitors, are used routinely in the treatment of primary headache disorders. Indomethacin is unique in its use in the diagnosis and treatment of hemicrania continua and paroxysmal hemicrania. The mechanism of this specific action is not fully understood, although an interaction with nitric oxide (NO) signaling pathways has been suggested. Trigeminovascular neurons were activated by dural electrical stimulation, systemic administration of an NO donor, or local microiontophoresis of L-glutamate. Using electrophysiological techniques, we subsequently recorded the activation of trigeminovascular neurons and their responses to intravenous indomethacin, naproxen, and ibuprofen. Administration of indomethacin (5 mg·kg-1), ibuprofen (30 mg·kg-1), or naproxen (30 mg·kg-1) inhibited dural-evoked firing within the trigeminocervical complex with different temporal profiles. Similarly, both indomethacin and naproxen inhibited L-glutamate-evoked cell firing suggesting a common action. By contrast, only indomethacin was able to inhibit NO-induced firing. The differences in profile of effect of indomethacin may be fundamental to its ability to treat paroxysmal hemicrania and hemicrania continua. The data implicate NO-related signaling as a potential therapeutic approach to these disorders.Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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