A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches

Oliver Summ, Anna P. Andreou, Simon Akerman, Peter Goadsby

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) that act as cyclo-oxygenase (COX) inhibitors are commonly used in the treatment of a range of headache disorders, although their mechanism of action is unclear. Indomethacin is of particular interest given its very special effect in some primary headaches. Here the in vivo technique of intravital microscopy in rats has been utilised as a model of trigeminovascular nociception to study the potential mechanism of action of indomethacin. Dural vascular changes were produced using electrical (neurogenic) dural vasodilation (NDV), calcitonin gene-related peptide (CGRP) induced dural vasodilation and nitric oxide (NO) induced dural vasodilation using NO donors. In each of these settings the effect of intravenously administered indomethacin (5 mg kg(-1)), naproxen (30 mg kg(-1)) and ibuprofen (30 mg kg(-1)) was tested. All of the tested drugs significantly inhibited NDV (between 30 and 52%). Whilst none of them was able to inhibit CGRP-induced dural vasodilation, only indomethacin reduced NO induced dural vasodilation (35 +/- A 7%, 10 min post administration). We conclude NSAIDs inhibit release of CGRP after NDV without an effect on CGRP directly. Further we describe a differentiating effect of indomethacin inhibiting nitric oxide induced dural vasodilation that is potentially relevant to understanding its unique action in disorders such as paroxysmal hemicrania and hemicrania continua.

Original languageEnglish
Pages (from-to)477-483
Number of pages7
JournalJournal of Headache and Pain
Volume11
Issue number6
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Trigeminal
  • NSAID
  • COX
  • Headache
  • Vasodilation
  • Rat
  • GENE-RELATED PEPTIDE
  • NONSTEROIDAL ANTIINFLAMMATORY DRUGS
  • DURAL MENINGEAL VESSELS
  • NITRIC-OXIDE
  • BLOOD-FLOW
  • INDUCED DILATION
  • IN-VITRO
  • RAT
  • PROSTAGLANDIN
  • MIGRAINE

Fingerprint

Dive into the research topics of 'A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches'. Together they form a unique fingerprint.

Cite this