THE ENDOGENOUS CANNABINOID ANANDAMIDE, BUT NOT THE CB2 LIGAND PALMITOYLETHANOLAMIDE, PREVENTS THE VISCERO-VISCERAL HYPERREFLEXIA ASSOCIATEDWITH INFLAMMATION OF THE RAT URINARY-BLADDER

Anandamide, an endogenous ligand at the CB1 cannabinoid receptor and p almitoylethanolamide (a putative endogenous ligand at the CB2 receptor ) have both been shown to possess anti-hyperalgesic properties in mode ls of somatic and visceral inflammation. In the turpentine-inflamed ra t urinary bladder a reversal of the inflammation-associated viscero-vi sceral hyperreflexia (WH) was observed when the cannabinoids were admi nistered 135 min after the induction of inflammation. Therefore, in th is study we determined the efficacy of these two N-acylethanolamides i n the prevention of VVH in the same model, using a prophylactic dosing regimen. Palmitoylethanolamide did not prevent the VVH (in the dose r ange 10-30 mg/kg, i.a), but anandamide attenuated the response in a do se related manner, with a threshold of 25 mg/kg (i.a). These findings provide further support for an acute anti-nociceptive and anti-hyperal gesic role for CB1 receptor agonists, with CB2 agonist effects only be coming important once the effects of inflammation are established. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.