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

Agmatine, an endogenous ligand, interacts both with the alpha(2)-adrenoceptors and with the imidazoline binding sites. The effect of intrathecally administered agmatine on carrageenan-induced thermal hyperalgesia was investigated by means of a paw-withdrawal test in rats. The effect of agmatine on morphine-induced anti-hyperalgesia was also studied. Intrathecal agmatine in doses larger than 250 mu g caused a decrease in the pain threshold, with vocalization and agitation lasting for several hours in all animals. Agmatine alone at 1-100 mu g did not give rise to any change in the thermal withdrawal threshold in the contralateral non-inflamed paw. Agmatine pretreatment was found to dose-dependently attenuate the thermal hyperalgesia induced by 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 (subeffective dose) has significantly higher anti-hyperalgesic effect then the individual compounds by themselves. These are the first data demonstrating the behavioral and anti-hyperalgesic effects of intrathecal agmatine. The results reveal important interactions between intrathecal agmatine and opioids in thermal hyperalgesia. (C) 1999 Elsevier Science B.V. All rights reserved.