PURPOSE:

Palmitoylethanolamide is both an endogenous mediator released together with the endocannabinoid anandamide from membrane phospholipids, and a plant-derived compound with analgesic and antinflammatory properties. Here, we verified if the pathophysiology of experimental cystitis involves changes in the levels of palmitoylethanolamide and of some of its targets [i.e. cannabinoid (CB1 and CB2) receptors, and PPARα] and if exogenous-administered palmitoylethanolamide can be proposed as a preventive measure for cystitis.

MATERIAL AND METHODS:

Cystitis was induced by cyclophosphamide in female rats. Nociceptive responses, voiding episodes, gross damage, myeloperoxidase activity, bladder weight, bladder palmitoylethanolamide and endocannabinoid levels (measured by liquid chromatography-mass spectrometry), and expression of palmitoylethanolamide targets (measured by quantitative reverse transcription-PCR) were recorded.

RESULTS:

Cyclophosphamide induced pain behaviour, bladder inflammation and voiding dysfunction associated to increased bladder levels of palmitoylethanolamide, up-regulation of CB1 receptors mRNA expression, down-regulation of PPARα mRNA and no changes in CB2 receptor mRNA expression. Exogenously-administered ultramicronized palmitoylethanolamide attenuated pain behaviour, voids and bladder gross damage. The CB1 antagonist rimonabant and the PPARα antagonist GW6471 counteracted the beneficial effect of palmitoylethanolamide on gross damage. Additionally, GW6471 further decreased voiding episodes in palmitoylethanolamide-treated rats.

CONCLUSIONS:

The present study provides strong evidence for a protective role of palmitoylethanolamide as well as for alteration of bladder palmitoylethanolamide levels (and of some of its targets) in cyclophosphamide-induced cystitis.
Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.