THE ANTI-HYPERALGESIC ACTIONS OF THE CANNABINOID ANANDAMIDE AND THE PUTATIVE CB2 RECEPTOR AGONIST PALMITOYLETHANOLAMIDE IN VISCERAL AND SOMATIC INFLAMMATORY PAIN

This study assessed the effects of two N-acylethanolamides in establis hed rat models of visceral and somatic inflammatory pain. (1) The ther apeutic effects of the cannabinoid anandamide and the putative CB2 ago nist palmitoylethanolamide were tested in a modal of persistent viscer al pain (turpentine inflammation of the urinary bladder). Both anandam ide (at a dose of 25 mg/kg) and palmitoylethanolamide (at doses of 10- 30 mg/kg) were able to attenuate the viscero-visceral hyper-reflexia ( VVH) induced by inflammation of the urinary bladder. (2) The effects o f the same compounds on the behavioural response to subcutaneous forma lin injection were assessed. The characteristic biphasic response was observed in control animals. Anandamide (dose range 5-25 mg/kg) and pa lmitoylethanolamide (dose range 5-10 mg/kg) both reduced the second ph ase of the response. The results confirm the analgesic potential of en dogenous ligands at cannabinoid receptor sites. The anti-nociceptive e ffect of the putative CB2 receptor agonist, palmitoylethanolamide, is particularly interesting since it is believed to be a peripherally med iated effect.This observation might be exploited to separate central p sychotropic effects from peripheral analgesic actions of the cannabino ids, under inflammatory conditions. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.