Titre du document / Document title

S(+)-flurbiprofen but not 5-HT₁ agonists suppress basal and stimulated CGRP and PGE₂ release from isolated rat dura mater

Auteur(s) / Author(s)

ZIMMERMANN K. ⁽¹⁾ ; REEH P. W. ⁽¹⁾ ; AVERBECK B. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Institute of Physiology and Experimental Pathophysiology, University of Erlangen-Nürnberg, Universitätsstr. 17, 91054 Erlangen, ALLEMAGNE

Résumé / Abstract

Neurogenic inflammation of the meninges, expressed in plasma extravasation and vasodilatation, putatively contributes to certain types of headache. Both, non-steroidal antiinflammatory drugs (NSAIDs) and serotonin-1 (5-HT₁) receptor agonists are similarly effective antimigraine drugs but their mechanism of action is unclear. The clinical observation that sumatriptan lowered plasma levels of calcitonin gene-related peptide (CGRP), found increased during migraine attacks, drew attention to a possible inhibition of pro-inflammatory neuropeptide release from trigeminal afferents. An isolated preparation of fluid-filled rat skull cavities was used to study effects of NSAIDs and 5-HT_1B/D agonists on the dura stimulated by inflammatory mediators (bradykinin, histamine and serotonin, 10^-5 M each). The release of immunoreactive CGRP (iCGRP) and immunoreactive PGE₂ (iPGE₂) was measured in 5-min samples of superfusates using enzyme immunoassays. S(+)-flurbiprofen (10^-6 M) strongly reduced the basal and stimulated iCGRP release and abolished iPGE₂ release; R(-)-flurbiprofen showed much less effect on iPGE₂ liberation and did not influence iCGRP release. The 5-HT_1B/D agonists naratriptan and CP93,129 were ineffective on both iCGRP and iPGE₂ release. Inspite of its weak COX blocking effect, R( - )-flurbiprofen is reported to exert antinociceptive effects, although it has not been tested in migraine. Only the potent COX blocker S(+)-flurbiprofen also suppressed iCGRP release while the 5-HT_1B/D agonists were ineffective. Thus, inhibition of meningeal neuropeptide secretion is not a common action principle of the drugs that could be essential for their antimigraine effects.

Revue / Journal Title

Pain   ISSN 0304-3959   CODEN PAINDB 

Source / Source

2003, vol. 103, n^o3, pp. 313-320 [8 page(s) (article)] (1 p.1/4)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1975) (Revue)

Mots-clés anglais / English Keywords

Enzyme ; Oxidoreductases ; Vertebrata ; Mammalia ; Rodentia ; Neurotransmitter ; Vascular disease ; Central nervous system disease ; Cerebral disorder ; Cerebrovascular disease ; Cardiovascular disease ; Neurological disorder ; Nervous system diseases ; Serotonin agonist ; Agonist ; Pain ; Prostaglandin-endoperoxide synthase ; Enzyme inhibitor ; Arylpropionic acid derivatives ; Animal ; Neuropeptide ; Rat ; Non steroidal antiinflammatory agent ; Calcitonin gene related peptide ; Migraine ; Sumatriptan ; Mechanism of action ; 5-HT1 Serotonine receptor ; Headache ; Extravasation ; Meninge ; Neurogenic inflammation ; Dura mater ; Release ; Flurbiprofen ;

Mots-clés français / French Keywords

Enzyme ; Oxidoreductases ; Vertebrata ; Mammalia ; Rodentia ; Neurotransmetteur ; Vaisseau sanguin pathologie ; Système nerveux central pathologie ; Encéphale pathologie ; Cérébrovasculaire pathologie ; Appareil circulatoire pathologie ; Trouble neurologique ; Système nerveux pathologie ; Stimulant sérotoninergique ; Agoniste ; Douleur ; Prostaglandin-endoperoxide synthase ; Inhibiteur enzyme ; Arylpropionique acide dérivé ; Animal ; Neuropeptide ; Rat ; Antiinflammatoire non stéroïde ; Peptide CGRP ; Migraine ; Sumatriptan ; Mécanisme action ; Récepteur sérotoninergique 5-HT1 ; Céphalée ; Extravasation ; Méninge ; Inflammation neurogène ; Dure mère ; Libération ; Flurbiprofène ;

Mots-clés espagnols / Spanish Keywords

Enzima ; Oxidoreductases ; Vertebrata ; Mammalia ; Rodentia ; Neurotransmisor ; Vaso sanguíneo patología ; Sistema nervosio central patología ; Encéfalo patología ; Vaso sanguíneo encéfalo patología ; Aparato circulatorio patología ; Trastorno neurológico ; Sistema nervioso patología ; Estimulante serotoninérgico ; Agonista ; Dolor ; Prostaglandin-endoperoxide synthase ; Inhibidor enzima ; Arilpropionico ácido derivado ; Animal ; Neuropéptido ; Rata ; Antiinflamatorio no esteroide ; Péptido CGRP ; Jaqueca ; Sumatriptán ; Mecanismo acción ; Receptor serotoninérgico 5-HT1 ; Cefalea ; Extravasación ; Meninge ; Inflamación neurógena ; Duramadre ; Liberación ; Flurbiprofeno ;

Mots-clés d'auteur / Author Keywords

Migraine ; Serotonin receptor agonist ; Non-steroidal antiinflammatory drug ; Neurogenic inflammation ; Neuropeptides ;

Localisation / Location

INIST-CNRS, Cote INIST : 17241, 35400011122703.0090