Adjuvant effect of caffeine on acetylsalicylic acid anti-nociception: prostaglandin E2 synthesis determination in carrageenan-induced peripheral inflammation in rat.
In the present study, we report a synergistic interaction between acetylsalicylic acid (ASA) and caffeine (CAF) on the inhibition of nociception in a model of peripheral inflammation in rat; on the contrary no interaction have been found on anti-inflammatory effects and peripheral prostaglandin E2 (PGE-2) synthesis inhibition. Acute inflammation was induced by the subplantar injection of carrageenan into the right hind paw, and the effects of the drugs were evaluated from 0 to 5h. Nociception was assessed using the Randall & Selitto test, and the inflammatory response by plethismometry. Oral administration of ASA (10-400mg/kg) induced dose-related anti-nociceptive and anti-inflammatory effects. On the other hand, oral CAF administration (5-50mg/kg) did not show a dose-related inhibitory effect, neither on the inhibition of nociception nor on the inflammatory response. To analyze a possible interaction between both drugs a dose-response curve to ASA plus a fixed dose of CAF (5mg/kg) was obtained 3h after the injection of carrageenan, when the inflammatory pain peaked. A fixed dose of CAF was able to improve the anti-nociceptive, but not the anti-inflammatory, effects of ASA. We also assessed, by enzyme immunoassay, the effects of the combination on peripheral PGE-2 levels: CAF did not alter the inhibitory effect of ASA on PGE-2 synthesis. Our results corroborate the well-known clinical effects of combining ASA and CAF; on the other hand, we rule out that prostaglandin synthesis inhibition at peripheral sites would be the mechanism responsible of the adjuvant anti-nociceptive effect of CAF.
Fernández-Dueñas
Víctor
V
Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine, University of Barcelona, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
Sánchez
Sílvia
S
Planas
Eulàlia
E
Poveda
Raquel
R
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005528:Foot; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002110:Caffeine; D002351:Carrageenan; D015232:Dinoprostone; D001241:Aspirin