Effect of intrathecal agmatine on inflammation-induced thermal hyperalgesia in rats

Agmatine, an endogenous ligand, interacts both with the alpha(2)-adrenocept ors and with the imidazoline binding sites. The effect of intrathecally adm inistered agmatine on carrageenan-induced thermal hyperalgesia was investig ated by means of a paw-withdrawal test in rats. The effect of agmatine on m orphine-induced anti-hyperalgesia was also studied. Intrathecal agmatine in doses larger than 250 mu g caused a decrease in the pain threshold, with v ocalization and agitation lasting for several hours in all animals. Agmatin e alone at 1-100 mu g did not give rise to any change in the thermal withdr awal threshold in the contralateral non-inflamed paw. Agmatine pretreatment was found to dose-dependently attenuate the thermal hyperalgesia induced b y intraplantar carrageenan. The effect of 100 mu g agmatine was completely lost by 60 min, whereas the effect of 50 mu g was of similar magnitude but exhibited a longer duration. Agmatine posttreatment had a slighter effect. Agmatine pretreatment (100 mu g) together with 1 mu g morphine (subeffectiv e dose) has significantly higher anti-hyperalgesic effect then the individu al compounds by themselves. These are the first data demonstrating the beha vioral and anti-hyperalgesic effects of intrathecal agmatine. The results r eveal important interactions between intrathecal agmatine and opioids in th ermal hyperalgesia. (C) 1999 Elsevier Science B.V. All rights reserved.