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    Differential actions of indomethacin: clinical relevance in headache

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    Author
    Summ, O.
    Andreou, A.P.
    Akerman, S.
    Holland, P.R.
    Hoffmann, J.
    Goadsby, P.J.
    Date
    2020-08-06
    Journal
    Pain
    Publisher
    Wolters Kluwer Health
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1097/j.pain.0000000000002032
    Abstract
    ABSTRACT: Nonsteroidal 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 Copyright 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.
    Keyword
    Trigeminal Autonomic Cephalalgias--drug therapy
    Ibuprofen
    Indomethacin
    Naproxen
    Models, Animal
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15239
    ae974a485f413a2113503eed53cd6c53
    10.1097/j.pain.0000000000002032
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