The antinociceptive interaction of anandamide and adenosine at the spinal level

Both anandamide and adenosine have significant roles in pain mechanisms, but no data are available concerning their interaction at the spinal level. The goal of this study was to determine how adenosine and the adenosine receptor antagonist caffeine affect the antinociceptive effect of anandamide. The pain sensitivity was assessed by the acute tail-flick test and by paw withdrawal test after carrageenan-induced inflammation. The substances were administered intrathecally to male Wistar rats. Anandamide alone (1, 30 and 100 microg) dose-dependently decreased the hyperalgesia, however it had low potency in the tail-flick test. Neither adenosine (100 microg) nor caffeine (400 microg) alone changed the pain sensitivity markedly. Their combination caused a short-lasting antihyperalgesia, but it did not influence the tail-flick latency. Both adenosine and caffeine decreased the antihyperalgesic potential of 100 microg anandamide, while adenosine-caffeine pretreatment temporarily enhanced its effect. As regards acute heat pain sensitivity, no combination with anandamide influenced the effect of anandamide. These findings provide new data concerning the interaction between two endogenous ligands and caffeine. Since these substances may exert effects on several receptors and/or systems, their interaction in vivo must be very complex and the net outcome after their coadministration could not been predicted from the in vitro results.