Differential actions of indomethacin: clinical relevance in headache.

Oliver Summ,Jan Hoffmann,Philip R. Holland,Anna P. Andreou,Simon Akerman,Peter J. Goadsby

doi:10.1097/j.pain.0000000000002032

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.

Highlights

Primary headache disorders represent a substantial component of neurological practice
The current study provides evidence of a substantial difference of the tested nonsteroidal anti-inflammatory drugs (NSAIDs)’ capabilities for blocking the sodium nitroprusside (SNP) infusioninduced effects in the trigeminocervical complex (TCC)
When comparing the effects of the NSAIDs on electrically induced cell firing within the TCC, it becomes clear that they have individual time-dependent profiles of action

Summary

Introduction

Primary headache disorders represent a substantial component of neurological practice. Nonsteroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, are used in headache therapy, such as in migraine,[26] in addition to their use in pain more broadly. They are distinguished by different chemical structures, eg, indomethacin is an acetic acid derivative, whereas ibuprofen is a propionic acid derivative; and by their profiles of absorption, metabolism, and Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Dr Akerman is with the Department of Neural and Pain Sciences, University of Maryland Baltimore, Baltimore, MD, United States, b Headache Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom

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