Faculty Collaboration Database

Attenuation of cystitis and pain sensation in mice lacking fatty acid amide hydrolase. J Mol Neurosci 2015 Apr;55(4):968-76

Date

11/07/2014

Pubmed ID

25374388

Pubmed Central ID

PMC4355044

DOI

10.1007/s12031-014-0453-x

Scopus ID

2-s2.0-84925538196 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

Endocannabinoids, such as N-arachidonoylethanolamine (AEA, also called anandamide), exert potent analgesic and anti-inflammatory effects. Fatty acid amide hydrolase (FAAH) is primarily responsible for degradation of AEA, and deletion of FAAH increases AEA content in various tissues. Since FAAH has been shown to be present in the bladder of various species, we compared bladder function, severity of experimental cystitis, and cystitis-associated referred hyperalgesia in male wild-type (WT) and FAAH knock-out (KO) mice. Basal concentrations of AEA were greater, and the severity of cyclophosphamide (CYP)-induced cystitis was reduced in bladders from FAAH KO compared to WT mice. Cystitis-associated increased peripheral sensitivity to mechanical stimuli and enhanced bladder activity (as reflected by increased voiding frequency) were attenuated in FAAH KO compared to WT mice. Further, abundances of mRNA for several pro-inflammatory compounds were increased in the bladder mucosa after CYP treatment of WT mice, and this increase was inhibited in FAAH KO mice. These data indicate that endogenous substrates of FAAH, including the cannabinoid AEA, play an inhibitory role in bladder inflammation and subsequent changes in pain perception. Therefore, FAAH could be a therapeutic target to treat clinical symptoms of painful inflammatory bladder diseases.

Author List

Wang ZY, Wang P, Hillard CJ, Bjorling DE

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amidohydrolases
Animals
Arachidonic Acids
Cystitis
Cytokines
Endocannabinoids
Inflammation
Male
Mice
Mice, Inbred C57BL
Nociception
Polyunsaturated Alkamides
RNA, Messenger
Urinary Bladder