title: Protective effect of palmitoylethanolamide in a rat model of cystitis.
abstract: OBJECTIVE
  PEA is an endogenous mediator released together with the endocannabinoid anandamide from membrane phospholipids. It is a plant derived compound with analgesic and anti-inflammatory properties. We verified whether the pathophysiology of experimental cystitis involves changes in the levels of PEA and of some of its targets, ie CB1 and CB2 receptors, and PPARα. We also determined whether exogenously administered PEA could be proposed as a preventive measure for cystitis.
  
  
  METHODS
  Cystitis was induced by cyclophosphamide in female rats. Nociceptive responses, voiding episodes, gross damage, myeloperoxidase activity, bladder weight, bladder PEA and endocannabinoid levels (measured by liquid chromatography-mass spectrometry) and the expression of PEA targets (measured by quantitative reverse transcriptase-polymerase chain reaction) were recorded.
  
  
  RESULTS
  Cyclophosphamide induced pain behavior, bladder inflammation and voiding dysfunction associated with increased bladder levels of PEA, up-regulation of CB1 receptor mRNA expression, down-regulation of PPARα mRNA and no change in CB2 receptor mRNA expression. Exogenously administered, ultramicronized PEA attenuated pain behavior, voids and bladder gross damage. The CB1 antagonist rimonabant and the PPARα antagonist GW6471 counteracted the beneficial effect of PEA on gross damage. Also, GW6471 further decreased voiding episodes in rats treated with PEA.
  
  
  CONCLUSIONS
  The current study provides strong evidence for a protective role of PEA as well as an alteration in bladder levels of PEA and of some of its targets in cyclophosphamide induced cystitis.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pessina
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Institute of Protein Biochemistry, National Research Council, Naples, Italy; National Institute of Optics, National Research Council, Pozzuoli, Italy; Endocannabinoid Research Group.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Institute of Protein Biochemistry, National Research Council, Naples, Italy; National Institute of Optics, National Research Council, Pozzuoli, Italy; Endocannabinoid Research Group.
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Naples, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy; National Institute of Optics, National Research Council, Pozzuoli, Italy; Endocannabinoid Research Group.
authors.forename: Teresa
authors.initials: T
authors.lastname: Aveta
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Naples, Italy; National Institute of Optics, National Research Council, Pozzuoli, Italy; Endocannabinoid Research Group.
authors.forename: Lorena
authors.initials: L
authors.lastname: Buono
authors.affiliation: Department of Life Science and Biotechnologies, University of Ferrara, Ferrara, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorenzani
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Naples, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy; National Institute of Optics, National Research Council, Pozzuoli, Italy; Endocannabinoid Research Group.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Naples, Italy; National Institute of Optics, National Research Council, Pozzuoli, Italy; Endocannabinoid Research Group.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Orlando
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Institute of Protein Biochemistry, National Research Council, Naples, Italy; National Institute of Optics, National Research Council, Pozzuoli, Italy; Endocannabinoid Research Group. Electronic address: aaizzo@unina.it.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
mesh_terms: D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000517:prevention & control*; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D010169:Palmitic Acids / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004983:Ethanolamines; D010169:Palmitic Acids; C005958:palmidrol; D003520:Cyclophosphamide
keywords: cannabinoid; cyclophosphamide; cystitis; interstitial; palmidrol; receptors; urinary bladder