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      NSAIDs in the Acute Treatment of Migraine: A Review of Clinical and Experimental Data

      review-article
      1 , 2 , *
      Pharmaceuticals
      MDPI
      migraine, NSAIDs, acetaminophen, aspirin, randomized controlled trials, experimental data

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          Abstract

          Migraine is a common disabling neurological disorder with a serious socio-economical burden. By blocking cyclooxygenase nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the synthesis of prostaglandins, which are involved in the pathophysiology of migraine headaches. Despite the introduction more than a decade ago of a new class of migraine-specific drugs with superior efficacy, the triptans, NSAIDs remain the most commonly used therapies for the migraine attack. This is in part due to their wide availability as over-the-counter drugs and their pharmaco-economic advantages, but also to a favorable efficacy/side effect profile at least in attacks of mild and moderate intensity. We summarize here both the experimental data showing that NSAIDs are able to influence several pathophysiological facets of the migraine headache and the clinical studies providing evidence for the therapeutic efficacy of various subclasses of NSAIDs in migraine therapy. Taken together these data indicate that there are several targets for NSAIDs in migraine pathophysiology and that on the spectrum of clinical potency acetaminophen is at the lower end while ibuprofen is among the most effective drugs. Acetaminophen and aspirin excluded, comparative trials between the other NSAIDs are missing. Since evidence-based criteria are scarce, the selection of an NSAID should take into account proof and degree of efficacy, rapid GI absorption, gastric ulcer risk and previous experience of each individual patient. If selected and prescribed wisely, NSAIDs are precious, safe and cost-efficient drugs for the treatment of migraine attacks.

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          Most cited references139

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          The International Classification of Headache Disorders: 2nd edition.

          (2004)
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            Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.

            Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.
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              Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model.

              Although the trigeminal nerve innervates the meninges and participates in the genesis of migraine headaches, triggering mechanisms remain controversial and poorly understood. Here we establish a link between migraine aura and headache by demonstrating that cortical spreading depression, implicated in migraine visual aura, activates trigeminovascular afferents and evokes a series of cortical meningeal and brainstem events consistent with the development of headache. Cortical spreading depression caused long-lasting blood-flow enhancement selectively within the middle meningeal artery dependent upon trigeminal and parasympathetic activation, and plasma protein leakage within the dura mater in part by a neurokinin-1-receptor mechanism. Our findings provide a neural mechanism by which extracerebral cephalic blood flow couples to brain events; this mechanism explains vasodilation during headache and links intense neurometabolic brain activity with the transmission of headache pain by the trigeminal nerve.
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                Author and article information

                Journal
                Pharmaceuticals (Basel)
                Pharmaceuticals (Basel)
                pharmaceuticals
                Pharmaceuticals
                MDPI
                1424-8247
                17 June 2010
                June 2010
                : 3
                : 6
                : 1966-1987
                Affiliations
                [1 ]Department of Neurology, University of Szeged, Semmelweis u. 6. Szeged, Hungary H-6720, Hungary; E-Mail: apardutz@ 123456yahoo.com (A.P.)
                [2 ]Headache Research Unit, Department of Neurology & GIGA Neurosciences, Liège University, CHU-Sart Tilman, T4(+1), B36, B-4000 Liège, Belgium
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: jschoenen@ 123456ulg.ac.be ; Tel: +32(0)43665190, Fax: +32(0)43665199.
                Article
                pharmaceuticals-03-01966
                10.3390/ph3061966
                4033962
                27713337
                780610a5-faf4-495c-bebf-e630a4656c30
                © 2010 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an Open Access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 27 April 2010
                : 18 May 2010
                : 11 June 2010
                Categories
                Review

                migraine,nsaids,acetaminophen,aspirin,randomized controlled trials,experimental data

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